[Standardized Valve Sparing Aortic Root Repair with Remodeling of Sinus of Valsalva].

The remodeling of sinus of Valsalva( Yacoub operation) is being standardized by adding annular fixation and technique for cusp prolapse as a refined method of valve sparing aortic root repair. It is important to design whole configurations of Valsalva sinus( diameters of aortic annulus and sino-tubular junction) according to the patient's geometric height (geometric height-oriented strategy). In this paper, we summarized our tips of remodeling of sinus of Valsalva operation.

Psychological Barriers to the Use of Opioid Analgesics for Treating Pain in Patients With Advanced Recurrent Cancer: A Multicenter Cohort Study.

Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75-2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale "disease progression" score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p = 0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale "harmful effects" (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids.Clinical Trial Registration Number UMIN000042443.

Multi-anode enhanced the bioelectricity generation in air-cathode microbial fuel cells towards energy self-sustaining wastewater treatment.

Microbial fuel cells (MFCs) hold considerable promise for harnessing the substantial energy resources present in wastewater. However, their practical application in wastewater treatment is limited by inadequate removal of organic matter and inefficient power recovery. Previous studies have investigated aeration as a method to enhance the removal of organic matter, but this method is energy-intensive. To address this issue, this study proposed using MFC-recovered bioelectricity for aeration, thereby mitigating the associated expenses. An air-cathode MFC with multi-anode was constructed and optimized to maximize electricity supply for aeration. Carbon-felt anodes were chosen as the most effective anode configuration, due to the high abundance of electroactive bacteria and genes observed in the biofilm generated on their surface. By incorporating six carbon felt anodes, the MFC achieved a 1.7 and 1.1 fold enhancement in the maximum power and current density, respectively. The optimized MFC unit achieved a stable current density of 0.32 A/m2 and achieved COD removal of 60% in the long-term operation of 140 days in a 50 L reactor. In a reactor scaled up to 1600 L, 72 MFCs successfully powered a mini air pump work for 10 s after an 81-s charging period. The intermittent aeration resulted in partial increases in DO concentrations to 0.03-3.5 mg/L, which is expected to promote the removal of nitrogen compounds by the nitrification-anammox process. These groundbreaking results lay the foundation for self-sustaining wastewater treatment technologies.

Ratio of the false lumen to the true lumen is associated with long-term prognosis after surgical repair of acute type A aortic dissection.

Objectives: The aim of this study was to assess potential predictors of aortic events after an emergency surgery for acute type A aortic dissection, especially paying attention to the findings of computed tomography (CT) performed immediately after the surgery. Methods: Between January 2001 and December 2015, 72 patients, who were diagnosed as having Stanford type A acute aortic dissection with a patent false lumen in the descending thoracic aorta, survived the emergency operation, and had postoperative CT scan data, were included in this study (mean follow-up, 8.2 ± 3.8 years; range 0.8-17.4 years). From the CT scan data, the diameter of the false lumen (FL-D) and true lumen (TL-D) were measured, and the FL-D:TL-D ratio was calculated. Long-term outcomes of the FL-D > TL-D group (n = 30) and the FL-D < TL-D group (n = 42) were compared. Results: In the late follow-up, 17 aortic events in the downstream aorta were observed. The FL-D:TL-D ratio (P = .01) was an adjusted risk of aortic events in multivariable analysis. The rates of freedom from aortic events at 5 and 9 years were superior in the FL-D < TL-D group than in the FL-D > TL-D group (92.0% and 88.6% vs 81% and 60.7%; log rank P < .05). Conclusions: Our results suggest that the false lumen:true lumen ratio predicts long-term prognosis after surgical repair of acute type A aortic dissection.

A normal pattern of mitral inflow predicts a better prognosis following cardiovascular events in early advanced-age patients.

Although a mitral inflow pattern usually changes from a normal pattern to an abnormal relaxation pattern as part of the aging process in healthy people, some early advanced-age individuals maintain a normal pattern. We investigated whether a normal pattern of mitral inflow predicts a better prognosis following cardiovascular (CV) events in early advanced-age patients. We enrolled 425 patients aged 60-65 years with 0.6 < E/A < 1.5. Patients were divided according to their mitral inflow pattern, i.e., a normal pattern group (E/A ≥ 1.0, n = 77) and an abnormal relaxation pattern group (E/A < 1, n = 348), and were evaluated the relationship with CV events. Multivariate regression analysis found that the normal inflow pattern was associated with odds ratios of 0.859 for body mass index (BMI; 95% confidence interval [CI]: 0.778-0.937), 0.529 for hypertension (0.303-0.924), and 0.325 for heart rate (0.228-0.463). During the follow-up period (4.9 ± 1.8 years), the adjusted-hazard ratio was significantly lower in the normal pattern group (HR: 0.119, 95% CI 0.016-0.910). Kaplan-Meier curves showed a higher event-free rate for the normal pattern group than for the abnormal relaxation pattern group (p = 0.0292). Normal inflow pattern in early advanced-age patients predicts a better prognosis following CV events.

Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study.

INTRODUCTION: Opioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer. METHODS AND ANALYSIS: This ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting. TRIAL REGISTRATION NUMBER: UMIN000042443.

Interventions for Shiga toxin-producing Escherichia coli gastroenteritis and risk of hemolytic uremic syndrome: A population-based matched case control study.

BACKGROUND: The role of antibiotics in the treatment of Shiga toxin-producing Escherichia coli (STEC) infection is controversial. OBJECTIVES: To evaluate the association between treatment (antibiotics, antidiarrheal agents, and probiotics) for STEC infection and hemolytic uremic syndrome (HUS) development. PATIENTS AND METHODS: We performed a population-based matched case-control study using the data from the National Epidemiological Surveillance of Infectious Diseases (NESID) between January 1, 2017 and December 31, 2018. We identified all patients with STEC infection and HUS as cases and matched patients with STEC infection without HUS as controls, with a case-control a ratio of 1:5. Further medical information was obtained by a standardized questionnaire. Multivariable conditional logistic regression model was used. RESULTS: 7760 patients with STEC infection were registered in the NESID. 182 patients with HUS and 910 matched controls without HUS were selected. 90 patients with HUS (68 children and 22 adults) and 371 patients without HUS (266 children and 105 adults) were included in the main analysis. The matched ORs of any antibiotics and fosfomycin for HUS in children were 0.56 (95% CI 0.32-0.98), 0.58 (0.34-1.01). The matched ORs for HUS were 2.07 (1.07-4.03), 0.86 (0.46-1.61) in all ages treated with antidiarrheal agent and probiotics. CONCLUSIONS: Antibiotics, especially fosfomycin, may prevent the development of HUS in children, while use of antidiarrheal agents should be avoided.

The pilot study of group robot intervention on pediatric inpatients and their caregivers, using 'new aibo'.

The study on robot-assisted therapy in a pediatric field has not been applied sufficiently in clinical settings. The purpose of this pilot study is to explore the potential therapeutic effects of a group robot intervention (GRI), using dog-like social robot (SR) 'aibo' in pediatric ward. GRI by aibo was conducted for those children with chronic illness (127 in total) who are hospitalized in National Centre for Child Health and Development (NCCHD), and their caregivers (116 in total), from March to April 2018. The observer made structured behavioural observation records, based on which qualitative research on the features of their words and conducts, were carried out. As a result, first, during the GRI, about 2/3 of total expression by children were positive, while about 1/4 were negative or inappropriate. On the other hand, as seen in the 'change' group, those children who had originally responded with negative expression eventually came to express positive expression, while getting involved in a ternary relationship or participating in a session more than once. Secondly, as for the expression from the caregivers during the GRI, active expressions such as 'participation' and 'exploration' accounted for the 2/3, while 1/3 turned out to be rather placid expressions such as 'watch over' or 'encourage.'Conclusion: There has not been any precedent study on the features of words and conducts expressed by patients and their caregivers during the GRI by aibo. The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting. What is Known: • The study on robot-assisted therapy in a pediatric field has only just begun. • Though many kinds of social robot have been reportedly used so far, none has yet to be applied in clinical settings What is New: • Our study revealed the features of words and behaviour expressed by the patients and their caregivers, when dog-like social robot 'aibo' was used for a group robot intervention in the pediatric ward. • The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting.

Children's daily lives and well-being: Findings from the CORONA-CODOMO survey 1st wave.

BACKGROUND: The coronavirus disease 2019 pandemic has changed people's lives dramatically. Few data on the acute effects of the pandemic on children's daily lives and well-being have been published to date. This study aimed to capture its effects on Japanese children during the first peak of the outbreak. METHODS: We conducted a web-based, anonymous cross-sectional survey targeting Japanese children aged 7-17 years and parents/guardians of children aged 0-17 years. Eligible individuals were invited to participate in the survey from April 30 to May 31, 2020. This self-report questionnaire examined daily life and behaviors, psychological symptoms, well-being, quality of life, and positive parenting or abusive behaviors at the very beginning of the outbreak. RESULTS: A total of 2,591 children and 6,116 parents/guardians participated in our survey. Sixty-two percent of children reported screen time exceeding 2 h. Twenty percent of children reported abusive behaviors by family members. Nine in ten parents/guardians of school-aged children reported that their child had at least one acute stress symptom in the past month. Average mental health subscale scores from KINDLR questionnaire on quality of life were lower than the national average for all grades. Nearly half of parents/guardians refrained from seeking medical care for the child's symptoms. CONCLUSIONS: The COVID-19 pandemic had serious acute impacts on Japanese children's daily lives, well-being, family relationships, and health-care utilization, including some impacts that are potentially long-lasting; thus, proactive interventions and services are needed, as well as longitudinal surveys.

Effects of Radiation on the Bone Strength of Spinal Vertebrae in Rats.

STUDY DESIGN: A controlled laboratory study. OBJECTIVE: The aim of this study was to examine bone damage caused by irradiation to spinal vertebrae in rats. SUMMARY OF BACKGROUND DATA: Radiotherapy is widely used in the treatment of malignant spine tumors. However, a few studies have reported vertebral fractures following radiotherapy as an adverse reaction. There are no reports on irradiation- induced changes in bone fragility, mechanical and structural changes focusing on the spine, and the mechanism of irradiation-induced bone osteoporosis. METHODS: Eighty-four female Wistar rats were randomly allocated to the 20 Gy irradiated or the nonirradiated (control) group. The lumbar vertebrae were irradiated with an external focal radiation dose of 20 Gy. Biomechanical, structural, and histological analyses were performed at 0, 2, 4, 6, 8, 12, and 24 weeks after irradiation. Structural analysis and bone density measurement of vertebral trabecular bone were performed by µCT. Histopathological evaluation was performed by hematoxylin and eosin staining and immunostaining. RESULTS: The bone strength at 2 weeks after irradiation (311 ±â€Š23 N) was 22% lower than that before irradiation (398 ±â€Š34 N) (P  < 0.05). The trabecular spacing increased, and trabecular connectivity and width decreased significantly in the irradiated group compared with those in the non-irradiated group. The three-dimensional structure model became coarse, and the trabecular structure continued to thin and disrupt after irradiation. There was no significant change in the bone mineral density in both groups. CONCLUSION: A decrease in bone strength was observed 2 weeks after irradiation. Bone mineral density remained unaltered, whereas the microstructure of trabecular bone changed, suggesting bone damage by irradiation.Level of Evidence: N/A.

Long-term results of modified bentall procedures: 18-year experience of the flanged technique.

OBJECTIVES: To evaluate the early and late outcomes of the modified Bentall procedure with the flanged technique. METHODS: We reviewed the medical records of 63 patients who had undergone root replacement by the modified Bentall procedure at our institute between January 2001 and December 2018. In most cases, we adopted a composite graft constructed with a mechanical valve or bioprosthesis and a Dacron graft by the flanged technique. Since 2011, we have used Valsalva grafts. RESULTS: Mean age 57 ± 16 years, range 16-80, male 43 cases. The mean follow-up was 75 ± 56 months (range 0-216). Through April 1, 2020, we could follow up on 61 cases (97%) within a six-month period. Hospital mortality was 7.9% (4.8% in elective cases). In late follow-up, eight deaths were observed. In the bio-Bentall group (n=26), no deaths or major adverse valve-related events (MARVEs) occurred. In the mechanical Bentall group (n=37), seven cases of MARVEs, including two cerebral hemorrhages and one cerebral embolism, were observed. All patients were free from MARVEs at 5 years post procedure in the bio-Bentall group, and 93.8% and 76.8% were event-free at 5 years and 10 years, respectively, in the mechanical Bentall group. CONCLUSIONS: The 18-year results of the modified Bentall procedure were acceptable, providing excellent outcomes in the bio-Bentall group. The flanged technique enabled the use of a larger prosthesis, which may have resulted in good durability with the bio-Bentall procedure.

Children with special health care needs and mothers' anxiety/depression: Findings from the Tokyo Teen Cohort study.

AIM: Children with special health care needs (CSHCN) are those who require more care for their physical, developmental, or emotional differences than their typically developing peers. Among a wide range of burdens that caregivers of CSHCN experience, the mental burden of caregivers is still not well investigated. This study aimed at examining the relationship between caring for CSHCN and mothers' anxiety/depression. METHODS: This study used data from the Tokyo Early Adolescence Survey, a population-based cross-sectional survey. Using screening questionnaires, we evaluated the prevalence of CSHCN and identified their primary caregivers. Focusing on mothers as caregivers, we analyzed the relationship between having CSHCN and mothers' anxiety/depression, and between the severity of children's condition and mothers' anxiety/depression. We further determined what mediates these relationships using path analyses. RESULTS: Among 4003 participants, we identified 502 CSHCN (12.5%), and 93% of responding caregivers were mothers. We found that mothers with CSHCN were significantly more anxious/depressed than those without CSHCN, which was closely related to the severity of children's condition. The mediation effect of social support on the relation between CSHCN and mothers' anxiety/depression was statistically significant. CONCLUSION: Mothers of CSHCN were more anxious/depressed than other mothers in this study. Social support was indicated to have a significant mediating effect on the relationship between CSHCN and mothers' anxiety/depression. Our results suggest that considering ways to offer social support may effectively relieve the mental stress experienced by mothers of CSHCN.

Tapentadol Safety and Patient Characteristics Associated with Treatment Discontinuation in Cancer Therapy: A Retrospective Multicentre Study in Japan.

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

Haemodynamic benefit of bridging use of bosentan prior to pulmonary endarterectomy.

OBJECTIVES: Some patients present with excessive pulmonary hypertension (PH) prior to pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study was performed to evaluate the clinical role of pretreatment before PEA in CTEPH patients. METHODS: A total of 370 patients with CTEPH undergoing first PEA between 2003 and 2017 were divided into those receiving pretreatment with bosentan (group B: n = 119) and those without targeted pretreatment for PH (group C: n = 251). After selecting patients given bosentan (2-8 months) and using propensity score matching, comparable patient cohorts (n = 23 each) were created from both groups. PEA was performed in the standard manner, and the median number of extracted segments was 14. RESULTS: There were no significant differences in perioperative demographic characteristics or 30-day mortality (overall 5.7%) between the groups before and after matching. In patients with preoperative pulmonary vascular resistance (PVR) ≥800 dynes s/cm5, a significantly larger decrease in PVR was found in group B (78%) compared to group C (68%) (P = 0.033). There was no significant difference in late survival between the groups after matching. The frequency of residual/persistent PH (mean pulmonary artery pressure >25 mmHg) was lower in group B than in group C, although the difference was not significant (22% vs 39%, respectively, P = 0.200). Advanced age and longer cardiopulmonary bypass time were independent predictors of both 30-day mortality and residual/persistent PH (odds ratio: age, 1.053, 1.013, cardiopulmonary bypass time, 1.065, 1.010, respectively). CONCLUSIONS: Preoperative treatment of CTEPH patients with bosentan for 2-8 months can improve post-PEA PVR without adverse clinical events in patients with a high preoperative PVR. A temporary bridging regime appears beneficial in selected patients prior to PEA.

Rhythm-control therapy for new-onset atrial fibrillation in critically ill patients: A post hoc analysis from the prospective multicenter observational AFTER-ICU study.

BACKGROUND: Sustained new-onset atrial fibrillation (AF) in the intensive care unit has been reported to be associated with poor outcomes. However, in critical illness, whether rhythm-control therapy can achieve sinus rhythm (SR) restoration is unknown. This study aimed to assess the impact of rhythm-control therapy on SR restoration for new-onset AF in critically ill patients. METHODS: This post-hoc analysis of a prospective multicenter observational study involving 32 Japan intensive care units compared patients with and without rhythm-control therapy for new-onset atrial fibrillation (AF) and conducted a multivariable analysis using Cox proportional hazards regression analysis including rhythm-control therapy as a time-varying covariate for SR restoration. RESULTS: Of 423 new-onset AF patients, 178 patients (42%) underwent rhythm-control therapy. Among those patients, 131 (31%) underwent rhythm-control therapy within 6 h after AF onset. Magnesium sulphate was the most frequently used rhythm-control drug. The Cox proportional hazards model for SR restoration showed that rhythm-control therapy had a significant positive association with SR restoration (adjusted hazard ratio: 1.46; 95% confidence interval: 1.16-1.85). However, the rhythm-control group had numerically higher hospital mortality than the non-rhythm-control group (31% vs. 23%, p = 0.09). CONCLUSIONS: Rhythm-control therapy for new-onset AF in critically ill patients was associated with SR restoration. However, patients with rhythm-control therapy had poorer prognosis, possibly due to selection bias. These findings may provide important insight for the design and feasibility of interventional studies assessing rhythm-control therapy in new-onset AF.

Reflected wave intensity increases based on aortic diameter after endovascular aortic therapy in a goat model.

Reflected wave increases after endovascular aortic repair (EVAR) in patients with aortic aneurysm. This affects the left ventricular (LV) diastolic function and leads to a poor prognosis. This study aimed to evaluate the relationship between increased reflected wave amplitude and aortic diameter after EVAR. EVAR was performed in seven healthy goats. We assessed wave intensity (WI), aortic diameter, and stiffness parameter ß. Moreover, we evaluated the relationship between negative reflected wave (NW, reflected waves toward the heart from the periphery by WI) and other parameters after EVAR. Results showed an increase in stiffness parameter ß (3.5 ± 0.3 vs 15.9 ± 4.7, p = 0.018) and a decrease in the change of aortic diameter (6.9 ± 0.7 vs 2.7 ± 0.4%, p = 0.018) after EVAR. The NW was significantly amplified after EVAR from baseline (-589.8 ± 143.4 to - 1192.3 ± 303.7 mmHg-m/sec3, p = 0.043). The NW showed a significant correlation with maximum aortic diameter (R = 0.707, p = 0.038) and minimum aortic diameter (R = 0.724, p = 0.033). The reflected wave was enhanced after EVAR and was correlated to the aortic diameter at the stent-graft site. It is important to consider that patients with smaller aortic diameters in landing zone who undergo EVAR may develop LV dysfunction.

Trajectories of Healthcare Utilization Among Children and Adolescents With Autism Spectrum Disorder and/or Attention-Deficit/Hyperactivity Disorder in Japan.

BACKGROUND: Early intervention and prevention of psychiatric comorbidities of children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are urgent issues. However, the differences in the diagnoses of ASD and ADHD and psychiatric comorbidities associated with age, long-term healthcare utilization trajectories, and its associated diagnostic features have not been fully elucidated in Japan. METHOD: We conducted a retrospective observational study using the medical records. Member hospitals of three major consortiums of hospitals providing child and adolescent psychiatric services in Japan were recruited for the study. Children who accessed the psychiatry services of the participating hospitals in April 2015 were followed up for 5 years, and data on their clinical diagnoses, consultation numbers, and hospitalizations were collected. Non-hierarchical clustering was performed using two 10-timepoint longitudinal variables: consultation numbers and hospitalization. Among the major clusters, the differences in the prevalence of ASD, ADHD, comorbid intellectual disability, neurotic disorders, and other psychiatric disorders were assessed. RESULTS: A total of 44 facilities participated in the study (59.5%), and 1,003 participants were enrolled. Among them, 591 diagnosed with ASD and/or ADHD (58.9%) and 589 without missing data were assessed. The mean age was 10.1 years, and 363 (70.9%) were boys. Compared with the pre-schoolers, the school-aged children and adolescents had fewer ASD, more ADHD, and fewer comorbid intellectual disability diagnoses, as well as more diagnoses of other psychiatric disorders. A total of 309 participants (54.7%) continued consultation for 2 years, and 207 (35.1%) continued for 5 years. Clustering analysis identified three, two, and three major clusters among pre-schoolers, school-aged children, and adolescents, respectively. The largest cluster was characterized by early termination of the consultation and accounted for 55.4, 70.6, and 73.4% of pre-schoolers, school-aged children, and adolescents, respectively. Among the school-aged children, the diagnosis of ADHD was associated with a cluster that required longer periods of consultations. Among the adolescents, comorbid psychiatric disorders other than intellectual disability and neurotic disorders were associated with clusters that required hospitalization. CONCLUSION: Continuous healthcare needs were common and psychiatric comorbidities were associated with complex trajectory among adolescents. The promotion of early intervention and prevention of comorbidities are important.

Research and Development Strategy for Future Embryonic Stem Cell-Based Therapy in Japan.

Herewith, we review an updated progress of regenerative medical products using human embryonic stem cells (ESCs) in Japan. Two groups from Kyoto University and the National Center for Child Health and Development (NCCHD) established a novel derivation/cultivation system of ESCs for potential application in translational and clinical research. At the first stage of ESC derivation, murine feeder cells have been used in line with Japanese guidelines on public health associated with the implementation of the xenograft. To avoid exposure of ESCs to animal products in culture media, a xeno-free cultivating system has been established. Twelve ESCs (KhES-1, KhES-2, KhES-3, KhES-4, KhES-5, SEES-1, SEES-2, SEES-3, SEES-4, SEES-5, SEES-6, and SEES-7) are now available under a clinically relevant platform for industrially and clinically applicable regenerative medical products. NCCHD submitted an investigative new drug application to the Pharmaceuticals and Medical Devices Agency (PMDA) for using ESC-based products in patients with hyperammonemia due to genetic defects on March 2018 under the Pharmaceutical Affairs Law (now revised to the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act). Currently, up to ten ESC-based products are being prepared for intractable and rare disorders in Japan.

Prevalence and associated factors of suicidality in Japanese adolescents: results from a population-based questionnaire survey.

BACKGROUND: Suicide is the leading cause of death among Japanese adolescents. However, knowledge gaps regarding contemporary demographics and factors associated with suicidality among Japanese adolescents are a major concern. This study examined the prevalence of suicidality among Japanese adolescents and investigated associated factors. METHODS: A population-based questionnaire survey investigating general health was administered to 22,419 adolescents aged 13-18 years. The 29-item questionnaire covered emotional status, family function, cyberbullying, suicidality, and stressors (e.g., relationships with parents/friends, school performance, and sexual identity). We conducted multiple logistic regression analysis to identify factors associated with suicidality in this population. RESULTS: The prevalence of suicidal ideation was 21.6% in males and 28.5% in females, and that of attempted suicide was 3.5% in males and 6.6% and in females. Bullying and stress related to family relationships had the strongest associations with suicidality. Exposure to cyberbullying had the highest odds ratio for both junior high (3.1, 95% confidence interval [CI] 2.1-4.4) and high school students (3.6, 95% CI 2.5-5.3). Other factors significantly associated with suicidality were sex, emotional status, and stress about relationships with friends, sexual identity, school records, and academic course. Adolescents accessed a variety of resources to cope with stressors, with the Internet being the most common resource consulted. CONCLUSIONS: Suicidality is commonly experienced among Japanese adolescents. Although there are many associated risk factors, cyberbullying is of particular concern. Recognition of factors associated with adolescent suicidality will inform further research and suicide prevention efforts for healthcare providers and families.