Dysbiosis in Gut Microbiota in Children Born Preterm Who Developed Autism Spectrum Disorder: A Pilot Study.

The gut microbiota was reported to differ between children with autism spectrum disorder (ASD) and typically developing (TD) children, and dysbiosis of the gut microbiota in preterm infants is common. Here, we explored the characteristics of gut microbiota in children born preterm with ASD. We performed 16S rRNA gene sequencing using stool samples from ASD children born preterm and TD children born preterm. Alpha diversity was significantly greater in the ASD group. A comparison of beta diversity showed different clusters. Linear discriminant analysis effect size analysis revealed significantly more Firmicutes in the ASD group compared with the TD group. In conclusion, the gut microbiota in children born preterm differs between children with ASD and TD.

Efficacious interventions for improving the transition readiness of adolescents and young adult patients with chronic illness: A narrative review of randomized control trials assessed with the transition readiness assessment questionnaire.

Objective: We inspected efficacious interventions to improve the transition readiness of adolescent and young adult patients with childhood-onset chronic illnesses using the Transition Readiness Assessment Questionnaire (TRAQ). Methods: Our narrative review was conducted on randomized control studies assessed with TRAQ for outcome measurement before and after the interventions. We included all patients with chronic diseases. We searched eight electronic database(s): Allied and Complementary Medicine Database (AMED) Allied and Complementary Medicine, BioSciences Information Service of Biological Abstracts (BIOSIS) Previews, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, Embase, Ichu-shi, Medline, and Web of Science. The text words for the search of data sources were as follows: "("transition readiness assessment questionnaire" OR TRAQ) AND 2011/01:2022/06[DP] AND (clinical AND trial OR clinical trials OR clinical trial OR random* OR random allocation)." More studies were identified from the references in our reported study. This data set was independently cross-checked by two reviewers. Results: We identified 261 reports and collected three articles. The target diseases were type-1 diabetes, congenital heart disease, cystic fibrosis, and inflammatory bowel disease. All the studies excluded patients with intellectual disabilities. The age of the participants was distributed between 12 and 20 years. Nurse-provided web-based intervention of transition readiness was constructed using digital resources in two studies. The intervention ranged from 6 to 18 months. All the interventions were efficacious in improving transition readiness assessed with TRAQ scores, except for the self-advocacy score. Conclusions: We obtained three randomized control studies with TRAQ for outcome measurement. In two studies, web-based and nurse-led organized interventions were shown to improve transition readiness.

Factors Surrounding the Healthcare Transition From Pediatric to Adult Care in 5p- Syndrome: A Survey Among Healthcare Professionals.

Background: The 5p- syndrome is associated with intellectual disturbance and physical complications from infancy, and patients continue treatment into adulthood. This study aimed to clarify the factors that facilitate and prevent healthcare transition from pediatric to adult care by conducting a questionnaire survey among medical professionals. Subjects: The survey included 81 medical professionals nominated by an association of families of 5p- patients in Japan. The questions involved medical care for 5p- syndrome in adulthood, experience of transition, and factors facilitating a patient's transition. Responses were obtained from 32 participants, with 27 answers eligible for analysis. Results: The questionnaire items involved physical symptoms and concerns regarding support and welfare prompting consult. The most common physical symptom was constipation. Regarding support and welfare, all participants had an experience of receiving consultation about care for the siblings of patients. Three (11.1%) participants had an experience of transition. Regarding the transition of patients with rare diseases or intellectual disturbance, only four (14.8%) believed that progress was being made in the transition. Discussion: Only 11% of the respondents experienced the transition of patients with 5p- syndrome. Because it is difficult for highly specialized adult care providers to deal with multidisciplinary complications of 5p- syndrome and information on prognosis and natural history is not known, it is presumed that the transition of 5p- syndrome did not progress. Factors to improve the transition of patients with 5p- syndrome and are likely to be effective for the transition of patients with other rare diseases or intellectual disabilities.

Psychogenic fever and postural tachycardia syndrome among school-aged children and adolescents with fever of unknown origin.

BACKGROUND: Although fever is a common symptom in pediatric practice, its origin is often unknown in pediatric patients. Psychogenic fever is a stress-related, psychosomatic disease observed especially in young women. This study aimed to estimate the prevalence of psychogenic fever in pediatric patients with fever of unknown origin by surveying the medical records of school-aged children and adolescents. METHODS: The study subjects included 47 patients aged 6-15 years who visited the Department of Pediatrics in Kansai Medical University Medical Center between January 2006 and December 2020 with fever of unknown origin. Data on age, sex, final estimated diagnosis, and comorbid psychosocial issues were collected from the medical records. RESULTS: The study was composed of 47 patients, including 22 male and 25 female patients (male/female ratio, 1:1.36). The mean age was 10.1 (standard deviation, 2.4) years for boys and 11.6 (standard deviation, 2.7) years for girls (p = .047). The final estimated diagnoses were psychogenic fever, physical disorder, infection of unknown origin, and miscellaneous in 18, 12, 12, and 5 patients, respectively. The most common comorbidity in these pediatric patients with psychogenic fever was postural tachycardia syndrome. CONCLUSION: Psychogenic fever was a common cause of fever of unknown origin in pediatric patients, and postural tachycardia was prevalent among children with psychogenic fever. Enhanced sympathetic response to stress might play an important role in both psychogenic fever and postural tachycardia.

Eye gaze differences in school scenes between preschool children and adolescents with high-functioning autism spectrum disorder and those with typical development.

BACKGROUND: Children with autism spectrum disorder (ASD) may experience difficulty adapting to daily life in a preschool or school settings and are likely to develop psychosomatic symptoms. For a better understanding of the difficulties experienced daily by preschool children and adolescents with ASD, this study investigated differences in eye gaze behavior in the classroom environment between children with ASD and those with typical development (TD). METHODS: The study evaluated 30 children with ASD and 49 children with TD. Participants were presented with images of a human face and a classroom scene. While they gazed at specific regions of visual stimuli, eye tracking with an iView X system was used to evaluate and compare the duration of gaze time between the two groups. RESULTS: Compared with preschool children with TD, preschool children with ASD spent less time gazing at the eyes of the human face and the object at which the teacher pointed in the classroom image. Preschool children with TD who had no classroom experience tended to look at the object the teacher pointed at in the classroom image. CONCLUSION: Children with ASD did not look at the human eyes in the facial image or the object pointed at in the classroom image, which may indicate their inability to analyze situations, understand instruction in a classroom, or act appropriately in a group. This suggests that this gaze behavior of children with ASD causes social maladaptation and psychosomatic symptoms. A therapeutic approach that focuses on joint attention is desirable for improving the ability of children with ASD to adapt to their social environment.

Human papillomavirus vaccination and postural tachycardia syndrome, deconditioning and exercise-induced hyperalgesia: An alternate interpretation of the reported adverse reactions.

Human papillomavirus vaccination (HPVV) was included in the national immunization program in 2013 in Japan. However, the Japanese government suspended proactive recommendations 2 months after this decision because various adverse events following the vaccination were reported by the media. More than 6 years have already passed since the suspension of proactive recommendations of all available vaccines in Japan. Although no causal relationship between the adverse effects and HPVV has been confirmed, the Japanese government has not withdrawn the suspension. Thus, it is important to show various possible causes of the adverse events other than HPVV. It is attempted to describe the possible contribution of the misunderstanding regarding the symptoms of postural tachycardia syndrome, deconditioning, and exercise-induced hyperalgesia as the adverse effects of HPVV in this review article.

Validation of the Japanese Transition Readiness Assessment Questionnaire.

BACKGROUND: For patients with childhood-onset chronic illnesses, the transition to adult care requires an understanding of transition readiness and the effectiveness of evaluation methods. However, no such psychometrically verified scales exist in Japan. This study aimed to develop a Japanese version of the Transition Readiness Assessment Questionnaire (TRAQ) and verify its validity and reliability. METHODS: The Japanese TRAQ was developed in accordance with international guidelines, followed by a preliminary survey to verify face validity among six participants who fulfilled the inclusion criteria. For the main survey 107 patients who fulfilled the same inclusion criteria were asked to complete the questionnaire and provide basic information. After descriptive statistics analysis, the construct validity of the Japanese TRAQ was tested using the t-test and Pearson's correlation coefficients. Cronbach's alpha coefficients were calculated to assess reliability. RESULTS: In the main survey, 76 participants with no missing data were included in the complete data analysis (40 males 36 females; mean age, 17.8 and 18.2 years, respectively). The mean total Japanese TRAQ score was 3.9. Cronbach's alpha coefficients were 0.94 overall and 0.8-0.96 for each of the four domains. The known-groups analysis revealed that older participants (r = 0.23, P = 0.044), those having knowledge of the disease name (yes [4.0] vs no [3.4]; P < 0.001), and making unaccompanied hospital visits (with parent/others [3.7] vs alone [4.4]; P < 0.001) had significantly higher total TRAQ scores. CONCLUSION: We confirmed preliminarily the validity and reliability of the Japanese TRAQ.

Spatiotemporal characteristics of gaze of children with autism spectrum disorders while looking at classroom scenes.

Children with autism spectrum disorders (ASD) who have neurodevelopmental impairments in social communication often refuse to go to school because of difficulties in learning in class. The exact cause of maladaptation to school in such children is unknown. We hypothesized that these children have difficulty in paying attention to objects at which teachers are pointing. We performed gaze behavior analysis of children with ASD to understand their difficulties in the classroom. The subjects were 26 children with ASD (19 boys and 7 girls; mean age, 8.6 years) and 27 age-matched children with typical development (TD) (14 boys and 13 girls; mean age, 8.2 years). We measured eye movements of the children while they performed free viewing of two movies depicting actual classes: a Japanese class in which a teacher pointed at cartoon characters and an arithmetic class in which the teacher pointed at geometric figures. In the analysis, we defined the regions of interest (ROIs) as the teacher's face and finger, the cartoon characters and geometric figures at which the teacher pointed, and the classroom wall that contained no objects. We then compared total gaze time for each ROI between the children with ASD and TD by two-way ANOVA. Children with ASD spent less gaze time on the cartoon characters pointed at by the teacher; they spent more gaze time on the wall in both classroom scenes. We could differentiate children with ASD from those with TD almost perfectly by the proportion of total gaze time that children with ASD spent looking at the wall. These results suggest that children with ASD do not follow the teacher's instructions in class and persist in gazing at inappropriate visual areas such as walls. Thus, they may have difficulties in understanding content in class, leading to maladaptation to school.

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n = 45) or aripiprazole (n = 47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8. Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8. All patients randomized to aripiprazole completed the study, and no serious adverse events were reported. Three patients in placebo group discontinued. Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents.

Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan.

The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as "carryover patients," who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term "transition" in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children's Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition.

The transition of adult patients with childhood-onset chronic diseases from pediatric to adult healthcare systems: a survey of the perceptions of Japanese pediatricians and child health nurses.

BACKGROUND: Advances in medical science have enabled many children with chronic diseases to survive to adulthood. The transition of adult patients with childhood-onset chronic diseases from pediatric to adult healthcare systems has received attention in Europe and the United States. We conducted a questionnaire survey among 41 pediatricians at pediatric hospitals and 24 nurses specializing in adolescent care to compare the perception of transition of care from pediatric to adult healthcare services for such patients. FINDINGS: Three-fourths of the pediatricians and all of the nurses reported that transition programs were necessary. A higher proportion of the nurses realized the necessity of transition and had already developed such programs. Both pediatricians and nurses reported that a network covering the transition from pediatric to adult healthcare services has not been established to date. CONCLUSIONS: It has been suggested that spreading the importance of a transition program among pediatricians and developing a pediatric-adult healthcare network would contribute to the biopsychosocial well-being of adult patients with childhood-onset chronic disease.

[Use of psychotropic agents for children with psychosomatic problems and developmental disorders].

A special consideration of psychotropic medication for children and adolescents in Japan is described. The use of all antidepressants and antianxiety drugs are "off-label". When using psychotropic drugs for the adolescents who complaint general fatigue, headache, or sleep disturbance, it should be confirmed the presence of the orthostatic disturbance (OD), because those drugs have the possibility of deteriorating the symptoms of OD. It is necessary to evaluate the risk and benefit for use of antidepressants in adolescents with major depression, considering the possibility of increasing suicide attempts. Long-acting methylphenidate and atomoxetine are regarded as the first line drugs for the treatment of children with attention deficit hyperactivity disorder. It is expected to solve "off-label" use and to establish clinical guidelines for the pharmacological treatment.

Japanese clinical guidelines for chronic pain in children and adolescents.

Chronic pain is a common problem in pediatric practice. The prevalence of chronic pain in children is >30%. Because pain indicates emotional expression as well as the physiological reaction toward infection, injury, and inflammation, both physiological and psychological assessments are essential to determine primary interventions for chronic pain. The Japanese Society of Psychosomatic Pediatrics Task Force of clinical practice guidelines for chronic pain in children and adolescents compiled clinical evidence and opinions of specialists associated with the primary care of pediatric chronic pain in the Japanese 'clinical guidelines for chronic pain in children and adolescents' in 2009, which are presented herein. The guidelines consist of three domains: general introduction to chronic pain; chronic abdominal pain; and chronic headache. Each section contains information on the physiological mechanism, psychological aspects, assessment methods, and primary interventions for pediatric chronic pain. These guidelines are expected to help disseminate knowledge on primary interventions for chronic pain in children and adolescents.

Two types of orthostatic dysregulation assessed by diameter of inferior vena cava.

AIMS: Orthostatic dysregulation (OD) is common in adolescents. This study was conducted to evaluate the usefulness of the measurement of the diameter of the inferior vena cava (IVC) for objective assessment of patients with OD. METHODS: Twenty children with OD (median 14 years, range 9-15 years) and 23 age-matched healthy children (median 12 years, range 10-15 years) were enrolled. A diameter of IVC was measured by an abdominal echogram before and after a head-up tilt table testing (HUT). Changes in IVC was assessed by an arbitrary parameter, collapse index (CI) as the following equation: [(maximal IVC diameter in the supine position - maximal IVC diameter in the standing position)/(maximal IVC diameter in the supine position)]× 100. CI was evaluated 4 weeks after treatment with an adrenergic agent. RESULTS: Children with OD demonstrated either higher CI or lower CI compared to that in control children: CI was more than 50 (range 50-71) in 12 patients with OD while that was equal to or less than 0 (range -225 to 0) in eight out of 20 patients. In contrast, CI was between 0 and 50 (range 1-26) in 23 healthy children. Pharmacological treatment induced the normalization in the CI in both higher and lower CI group. CONCLUSION: OD can be classified into two subtypes: by HUT, one is characterized by an increase of IVC diameter while another is characterized by its decrease. Measurement of IVC diameter by HUT is useful to understand the pathophysiology and to assess the efficacy of treatment.

Effects of interview on mood status of pregnant women with high-risk delivery.

BACKGROUND: Expectant mothers at high risk for preterm labor admitted to the Mother and Child Health Centers (MCH) often have psychological problems and mood disturbances. The purpose of the present study was to evaluate the effects of an interview by health professionals on their mood status. METHODS: Participants consisted of 52 women admitted to the MCH of Kansai Medical University (KMU) hospital and who had delivered between December 2006 and September 2007. Interview sessions by health professionals consisting of a neonatologist and a clinical psychologist, termed 'KMU baby doctor-team interview', were held once a week. During the interview the neonatologist discussed the physiology of preterm infants and treatment for the possible complications while the clinical psychologist listened to the expectant mothers talk about their anxieties or complaints and responded to their requests as much as possible. To investigate their mood status objectively, the participants were asked to complete the Japanese version of the Profile of Mood States (POMS) before and after the first session. RESULTS: On admission, more than 20% of participants ranging from 19 to 42 years of age had mood disturbances in Tension-Anxiety, Depression-Dejection, and Vigor categorized by POMS. The average score for Depression-Dejection, however, significantly improved after the first interview sessions. CONCLUSIONS: Mood disturbances were observed in a considerable number of expectant mothers at high risk for preterm labor. Interviews by health professionals consisting of a neonatologist and a clinical psychologist may alter their mood status.

Japanese clinical guidelines for juvenile orthostatic dysregulation version 1.

This clinical practice guideline provides recommendations for the assessment, diagnosis and treatment of school-aged children and juveniles with orthostatic dysregulation (OD), usually named orthostatic intolerance in USA and Europe. This guideline is intended for use by primary care clinicians working in primary care settings. The guideline contains the following recommendations for diagnosis of OD: (i) initial evaluation composed of including and excluding criteria, the assessment of no evidence of other disease including cardiac disease and so on; (ii) a new orthostatic test to determine four different subsets: instantaneous orthostatic hypotension, postural tachycardia syndrome, neurally mediated syncope and delayed orthostatic hypotension; (iii) evaluation of severity; and (iv) judgment of psychosocial background with the use of rating scales. The guideline also contains the following recommendations for treatment of OD on the basis of the result of an orthostatic test in addition to psychosocial assessment: (i) guidance and education for parents and children; (ii) non-pharmacological treatments; (iii) contact with school personnel; (iv) use of adrenoceptor stimulants and other medications; (v) strategies of psychosocial intervention; and (vi) psychotherapy. This clinical practice guideline is not intended as a sole source of guidance in the evaluation of children with OD. Rather, it is designed to assist primary care clinicians by providing a framework for decision making of diagnosis and treatments.