Xenograft of human pluripotent stem cell-derived cardiac lineage cells on zebrafish embryo heart.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) are a promising cell source for regenerative medicine and drug discovery. However, the use of animal models for studying human cardiomyocytes derived from hiPSCs in vivo is limited and challenging. Given the shared properties between humans and zebrafish, their ethical advantages over mammalian models, and their immature immune system that is rejection-free against xenografted human cells, zebrafish provide a suitable alternative model for xenograft studies. We microinjected fluorescence-labeled cardiac lineage cells derived from hiPSCs, specifically mesoderm or cardiac mesoderm cells, into the yolk and the area proximal to the outflow tract of the linear heart at 24 hours post-fertilization (hpf). The cells injected into the yolk survived and did not migrate to other tissues. In contrast, the cells injected contiguous with the outflow tract of the linear heart migrated into the pericardial cavity and heart. After 1 day post injection (1 dpi, 22-24 hpi), the injected cells migrated into the pericardial cavity and heart. Importantly, we observed heartbeat-like movements of some injected cells in the zebrafish heart after 1 dpi. These results suggested successful xenografting of hiPSC-derived cardiac lineage cells into the zebrafish embryo heart. Thus, we developed a valuable tool using zebrafish embryos as a model organism for investigating the molecular and cellular mechanisms involved in the grafting process. This is essential in developing cell transplantation-based cardiac therapeutics as well as for drug testing, notably contributing to advancements in the field of cardio-medicine.

Thyroid and endostyle development in cyclostomes provides new insights into the evolutionary history of vertebrates.

BACKGROUND: The endostyle is an epithelial exocrine gland found in non-vertebrate chordates (amphioxi and tunicates) and the larvae of modern lampreys. It is generally considered to be an evolutionary precursor of the thyroid gland of vertebrates. Transformation of the endostyle into the thyroid gland during the metamorphosis of lampreys is thus deemed to be a recapitulation of a past event in vertebrate evolution. In 1906, Stockard reported that the thyroid gland in hagfish, the sister cyclostome group of lampreys, develops through an endostyle-like primordium, strongly supporting the plesiomorphy of the lamprey endostyle. However, the findings in hagfish thyroid development were solely based on this single study, and these have not been confirmed by modern molecular, genetic, and morphological data pertaining to hagfish thyroid development over the last century. RESULTS: Here, we showed that the thyroid gland of hagfish undergoes direct development from the ventrorostral pharyngeal endoderm, where the previously described endostyle-like primordium was not found. The developmental pattern of the hagfish thyroid, including histological features and regulatory gene expression profiles, closely resembles that found in modern jawed vertebrates (gnathostomes). Meanwhile, as opposed to gnathostomes but similar to non-vertebrate chordates, lamprey and hagfish share a broad expression domain of Nkx2-1/2-4, a key regulatory gene, in the pharyngeal epithelium during early developmental stages. CONCLUSIONS: Based on the direct development of the thyroid gland both in hagfish and gnathostomes, and the shared expression profile of thyroid-related transcription factors in the cyclostomes, we challenge the plesiomorphic status of the lamprey endostyle and propose an alternative hypothesis where the lamprey endostyle could be obtained secondarily in crown lampreys.

Evolution of the nitric oxide synthase family in vertebrates and novel insights in gill development.

Nitric oxide (NO) is an ancestral key signalling molecule essential for life and has enormous versatility in biological systems, including cardiovascular homeostasis, neurotransmission and immunity. Although our knowledge of NO synthases (Nos), the enzymes that synthesize NO in vivo, is substantial, the origin of a large and diversified repertoire of nos gene orthologues in fishes with respect to tetrapods remains a puzzle. The recent identification of nos3 in the ray-finned fish spotted gar, which was considered lost in this lineage, changed this perspective. This finding prompted us to explore nos gene evolution, surveying vertebrate species representing key evolutionary nodes. This study provides noteworthy findings: first, nos2 experienced several lineage-specific gene duplications and losses. Second, nos3 was found to be lost independently in two different teleost lineages, Elopomorpha and Clupeocephala. Third, the expression of at least one nos paralogue in the gills of developing shark, bichir, sturgeon, and gar, but not in lamprey, suggests that nos expression in this organ may have arisen in the last common ancestor of gnathostomes. These results provide a framework for continuing research on nos genes' roles, highlighting subfunctionalization and reciprocal loss of function that occurred in different lineages during vertebrate genome duplications.

Discontinuation of tyrosine kinase inhibitors in pediatric chronic myeloid leukemia.

BACKGROUND: The feasibility of tyrosine kinase inhibitor (TKI) discontinuation in pediatric chronic myeloid leukemia (CML) remains to be fully elucidated. PROCEDURES: TKI was prospectively discontinued in patients who were diagnosed with CML at <20 years of age, treated with TKI for ≥3 years, and sustained molecular response 4.0 (MR4.0) for ≥2 years. Molecular relapse was defined as a single loss of major molecular response (MMR) (BCR-ABL1IS >0.1%). Relapsed patients resumed the same TKI therapy administered before discontinuation. RESULTS: Twenty-two patients with chronic-phase CML were enrolled, and the median ages at diagnosis and at TKI discontinuation were 9 (range: 1-14) years and 16 (5-26) years, respectively. The median follow-up time after TKI discontinuation was 37 months (range: 24-41 months). The median duration of TKI treatment before discontinuation was 100 (42-178) months, and that of MR4.0 was 53.5 (25-148) months. The treatment-free remission (TFR) rate at 12 months was 50.0% (90% confidence interval: 31.7%-65.8%). Eleven patients experienced loss of MMR within 4 months after TKI discontinuation and resumed TKI as originally prescribed. No progression was observed, and all 11 patients regained MR4.0 after TKI resumption. No patient had a withdrawal syndrome. The quality-of-life analysis suggested that successful TFR may improve academic performance in some patients. In patients who discontinued TKI therapy before puberty, the possibility of improvement in growth velocity upon TKI discontinuation was observed. CONCLUSIONS: TKI could be discontinued safely in patients with pediatric CML showing a sustained deep MR.

Development and validation of a Japanese version of the TRANSITION-Q.

BACKGROUND: The evaluation of transition readiness is indispensable for long-term follow-ups of adolescent patients with childhood-onset chronic diseases (CCD). We developed a Japanese version of the TRANSITION-Q (TRANSITION-Q-J) and used it to assess Japanese patients with CCD. METHODS: The TRANSITION-Q-J was developed through forward and backward translations followed by cognitive interviews with five adolescent patients. The field test was conducted with 125 adolescent patients, and a retest was conducted with 113 adolescent patients. RESULTS: Confirmatory factor analysis supported the two-factor analysis model including F1 (communication and self-management) and F2 (examination behavior). Sufficient internal consistency and test-retest reliability were demonstrated among the total 14 items, F1, and F2 (Cronbach's α > 0.80, intraclass correlation coefficient > 0.85). Convergent and discriminant validity for the 14 items and F1 were acceptable; however, F2 did not correlate significantly with the Rosenberg Self-Esteem Scale and Independent Consciousness Scale. Regarding known-groups validity, the older group had a significantly higher mean TRANSITION-Q-J score (50.05) than the younger group (43.28; P = 0.04). The same results were found for both F1 and F2. CONCLUSIONS: The TRANSITION-Q-J for adolescent patients with CCD was developed and its reliability and validity were verified. This scale is easy to administer. In addition to being a tool for transition period support, it could be used to verify effective factors and in program outcome evaluation, including intervention studies.

Validation study of the Japanese version of MD Anderson Symptom Inventory for Brain Tumor module.

OBJECTIVE: The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). METHODS: Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. RESULTS: Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5-30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach's coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test-retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. CONCLUSIONS: The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

Reliability and validity of a Japanese version of the psychosocial assessment tool for families of children with cancer.

BACKGROUND: Patients with childhood cancer and their families frequently experience psychosocial distress associated with cancer and its treatment. We thus examined the reliability and validity of a Japanese version of the Psychosocial Assessment Tool, which was designed to screen for psychosocial risk factors among families of children with cancer. METHODS: Forward-backward translation was used to develop the Japanese version of the Psychosocial Assessment Tool. We conducted a cross-sectional study. Mothers (N = 117), who were the primary caregivers of children with cancer, completed the Japanese version of the Psychosocial Assessment Tool and other measures to establish validity. The internal consistency and 2-week test-retest reliability of the Japanese version of the Psychosocial Assessment Tool were also examined. RESULTS: The internal consistency of the Japanese version of the Psychosocial Assessment Tool total score was sufficient (Kuder-Richardson 20 coefficient = 0.84); however, the subscales 'structure and resources,' 'stress reactions' and 'family beliefs' were less than optimal (Kuder-Richardson 20 coefficients = 0.03, 0.49 and 0.49, respectively). The test-retest reliability for the Japanese version of the Psychosocial Assessment Tool total score was sufficient (intraclass correlation coefficient = 0.92). Significant correlations with the criteria measures indicated the validity of the Japanese version of the Psychosocial Assessment Tool total score. The optimal cut-off score for screening mothers with high psychosocial risk was 0.9/1.0, which was associated with 92% sensitivity and 63% specificity. CONCLUSIONS: This study indicated that the Japanese version of the Psychosocial Assessment Tool is a valid and reliable tool to screen mothers for elevated distress.

Comparison of child and family reports of health-related quality of life in pediatric acute lymphoblastic leukemia patients after induction therapy.

BACKGROUND: This study aims at determining the health-related quality of life (HRQOL) of children with acute lymphoblastic leukemia (ALL) after the induction therapy, assessing the agreement between child self-reports and family proxy-reports HRQOL, and determining the factors related to this agreement, especially child age, family attendance, and children's social relationships beyond the family. METHODS: We analyzed questionnaire data (2012-2017) from the Japanese Pediatric Leukemia/Lymphoma Study Group's clinical study (ALL-B12). Participants were children with B-cell precursor ALL aged 5-18 and their family members, who mostly took care of the child during hospitalization. Participants answered the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales (PedsQL-G), and Cancer Module (PedsQL-C) to measure pediatric HRQOL. We calculated the differences between child self-reported and family proxy-reported subscale scores along with intraclass correlation coefficients (ICC). We conducted multiple regression analyses according to all participant pairs and age groups (young children, school age, and adolescents), with ICCs for all PedsQL-G subscales (ICC-G) and all PedsQL-C subscales (ICC-C) as the outcome variables. RESULTS: Five hundred twenty-two pairs of children and their families were analyzed. We observed a moderate level of agreement on most PedsQL subscales between child self-reports and family proxy-reports; however, worry had the weakest agreement for all PedsQL subscales (ICC = .32, 95% confidence interval = .24-.40). The agreement of ICC-C was positively related to family attendance in the hospitalization, only for the young children group (B = .185, p = .003). CONCLUSIONS: We observed some differences between child self-reports and family proxy-reports of HRQOL of children with ALL. Both child self-reports and family proxy-reports captured HRQOL in the induction therapy. We suggest that attending to young children's hospitalization affects the level of agreement between reports on their HRQOL.

Impacts of physical late effects on presenteeism in childhood cancer survivors.

BACKGROUND: Many childhood cancer survivors (CCSs) experience physical late effects related to their cancer types and treatment modalities. Physical late effects are an important factor in various occupational outcomes among CCSs. However, the relationship between physical late effects and presenteeism has remained unclear. This study aimed to estimate the impacts of physical late effects on presenteeism among employed CCSs. METHODS: Childhood cancer survivors replied to a questionnaire regarding presenteeism, and their attending physicians assessed their physical late effects between September 2014 and December 2015. The Work Limitations Questionnaire was used to measure presenteeism. Propensity score analysis and a generalized linear model were used to adjust covariates related to physical late effects and / or presenteeism. RESULTS: Of the 125 questionnaires distributed, 114 were returned. The data from 61 employed CCSs were analyzed. After controlling for covariates by propensity score analysis and generalized linear model, there were no significant differences in presenteeism between employed CCSs with either no or single physical late effects. However, employed CCSs with multiple physical late effects reported higher scores in Output (Estimate = 9.3, P = 0.041), Physical Demands (Estimate = 12.2, P = 0.020), and Productivity Loss scores (Estimate = 2.4, P = 0.045) on the Work Limitations Questionnaire than employed CCSs with no physical late effects. CONCLUSIONS: Employed CCSs with multiple physical late effects were at an increased risk for presenteeism. Healthcare and social welfare systems should be established to provide vocational assistance for CCSs after being employed to alleviate presenteeism.

Validation of family conflict scales for family caregivers of persons with dementia in long-term care facilities and exploration of family conflicts and support.

ABSTRACTBackground:The aim of the study was to develop a family conflict scale for family caregivers of persons with dementia in long-term care facilities and to explore the relationship between family conflicts and family support. METHODS: The scale was developed through forward- and back-translations, interviews with 12 staff members in long-term care facilities, and cognitive interviews with 12 family caregivers who met operational definitions in this study. The test was conducted with 334 family caregivers and a retest was conducted with 318 family caregivers who had indicated willingness to participate further. RESULTS: The internal consistency was relatively high for all subscales (Cronbach's α >0.87); sufficient retest reliability was demonstrated for all subscales (intraclass correlation coefficient >0.69). Confirmatory factor analysis supported a three-factor model. Convergent and discriminant validity for each of the family conflict scale subscales, family APGAR, and the Symptom Check List-90 Items-Revised were acceptable. Family caregivers who received no family assistance for caregiving perceived more conflict in their family than those receiving family assistance. CONCLUSIONS: The Japanese version of the family conflict scale for family caregivers of persons with dementia in long-term care facilities was developed. The reliability and validity of the scale were verified. When providing support to family caregivers in long-term care facilities, it is necessary to consider the family from multiple viewpoints, including family conflicts and support conditions from other family members.

Employment status and termination among survivors of pediatric brain tumors: a cross-sectional survey.

BACKGROUND: Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors' employment status. METHODS: A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants' first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. RESULTS: Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). CONCLUSION: Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

Quality of life after living donor liver transplant for biliary atresia in Japan.

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant-specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT). METHODS: A cross-sectional survey using anonymous questionnaires was completed between April and July 2015. Patient medical records were accessed. The Japanese version of Pediatric Quality of Life InventoryTM Generic Core Scales and Transplant Modules (child self-report and parent proxy-report) was administered. RESULTS: Participants consisted of 75 patients (mean age at survey, 9.6 years) and 74 parents. Japanese patients reported higher generic and transplant-specific HRQOL (total score) than that reported by US patients with BA after LT (US I; age at survey, 7.2 years) and by US patients after solid organ transplant (US II; age at survey, 11.3 years; LT, 53.8%; effect size, 0.55-0.96). Japanese parents, however, rated their children's generic HRQOL (total score) similar to that rated by the US I and II parents (0.13 and 0.30, respectively) and reported lower transplant-specific HRQOL (total score) than that reported by US II (0.26). Although the number of types of prescribed drugs was a common factor in HRQOL, most demographic and medical factors (e.g. child's age at survey and consultation frequency) varied with reporter (i.e. patients and parents). CONCLUSIONS: The levels and factors of generic and transplant-specific HRQOL of Japanese pediatric and adolescent patients with BA after LDLT varied with reporter (i.e. patients or parents).

Development of the Japanese version of the Pediatric Quality of Life Inventory™ Transplant Module.

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. METHODS: Based on the PedsQL linguistic validation process, the Japanese version of the PedsQL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. RESULTS: Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. CONCLUSIONS: Excellent feasibility, reliability, and validity of this Japanese self-report version of the PedsQL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the PedsQL Transplant Module is appropriate for use in clinical and research settings.

Factors influencing mother-child communication about fathers with neurobehavioural sequelae after brain injury.

OBJECTIVE: The present study clarified factors related to mother-child communication openness when fathers suffer neurobehavioural sequelae after stroke or traumatic brain injury. RESEARCH DESIGN: A cross-sectional study using self-report anonymous questionnaires was conducted. METHODS AND PROCEDURES: Forty-one mothers with 6-22-year-old children participated. The questionnaire examined personal factors (mother's psychological distress), social/family factors (family support functioning), illness-related factors (father's time at home and neurobehavioural sequelae severity) and mother's perceived level of open communication. Multiple regression was used to analyse factors related to mother-child communication openness. RESULTS: Mother-child open communication was explained by family support functioning (ß = 0.449), father's time at home (ß = -0.325) and mother's psychological distress (ß = -0.303). Neurobehavioural sequelae severity was not associated with mother-child open communication. CONCLUSIONS: Personal, social/family and illness-related factors were related to mother-child communication about paternal illness. Professionals should promote optimal family support functioning, connect families with external resources and assess families' interaction processes.

Physio-psychological Burdens and Social Restrictions on Parents of Children With Technology Dependency are Associated With Care Coordination by Nurses.

PURPOSE: To determine the association between parental care burdens and care coordination provided by nurses for children with technology dependency, specifically regarding physio-psychological burdens and social restrictions. DESIGN AND METHODS: A cross-sectional study was conducted between October and November 2015. Participants were recruited via home-visit nursing stations, social worker offices, and special-needs schools. A total of 246 parents of children with technology dependency completed anonymous self-report questionnaires. Parental burden was measured using the Zarit Burden Interview. Care coordination for children with technology dependency was examined using items extracted from focus group interviews involving three nursing administrators at home-visit nursing stations, two social workers, and a coordinator of school education for children with special health care needs. Multiple regression analysis was performed to examine the relationship between parental burden and care coordination among 172 parents who contracted with visiting nurses. RESULTS: Parents and children with nursing support were significantly younger and had higher medical care needs and higher parental role strain than those without nursing support. Care coordination from nurses predicted reduced parental burden, role strain, and personal strain (ß=-0.247, p=0.002; ß=-0.272, p=0.001; ß=-0.221, p=0.009, respectively). CONCLUSION: Nurses' care coordination appears to be associated with a reduction in parents' care burden resulting from home medical care of children with technology dependency, especially the social restrictions and physio-psychological burdens. PRACTICE IMPLICATIONS: Strengthening nursing functioning as care coordinators may contribute to reducing care burdens for parents of children with technology dependency.

Support for school reentry and relationships between children with cancer, peers, and teachers.

BACKGROUND: Returning to school after a cancer diagnosis can be socially challenging for children with cancer. This study investigated the form of support for school reentry and the associations with social support from peers and teachers. METHODS: This was a multicenter cross-sectional study. Children with cancer and their guardians completed questionnaires. Their guardians also underwent a semi-structured interview to describe the background of support for school reentry. RESULTS: Thirty-nine children with cancer and guardian dyads completed questionnaires and three guardians underwent semi-structured interview. Peer visits and their understanding of hospital experiences and how to interact with children were related to social support from peers. Teachers' understanding of physical appearance, academic performance, hospital experience and of how to interact with children was related to social support from peers. Teachers' understanding of diagnosis/treatment, academic performance and their status as the liaison between doctors/nurses in hospitals and teachers in local schools were also related to social support from teachers. Furthermore, children with cancer were also encouraged to establish supportive relationships with peers and teachers as a result of school reentry support that (i) helped children to feel that they are still members of the local school; (ii) improved peer and teacher understanding of the long-term recovery process of children with cancer; and (iii) facilitated the children's own awareness that they are fighting the disease. CONCLUSIONS: The multidisciplinary team consisting of the children with cancer, their families, doctors, nurses and teachers in the local school need to communicate with peers regarding positive experiences of fighting, and overcoming, severe disease.

Premenstrual Distress Among Japanese High School Students: Self-Care Strategies and Associated Physical and Psychosocial Factors.

This study aimed to identify self-care strategies and assess physical and psychosocial factors associated with premenstrual distress among high school students. A cross-sectional survey of 217 adolescent girls aged 15 to 18 years was conducted in October 2009. Most (84.3 percent) had at least one or more symptoms of premenstrual distress. Premenstrual distress interfered with normal school activity in 51.2 percent. Most participants (57.1 percent) did not perform any self-care strategies for premenstrual distress. A hierarchical multiple linear regression analysis was conducted. Comprehension of one's own physical and mental states during premenstrual phases mediated the relationship between neuroticism and premenstrual distress. Activity restrictions due to menstrual distress mediated the relationship between the family's understanding of one's behavior during premenstrual phases and premenstrual distress. Findings suggest that, even if girls have neuroticism, it will be important to teach them to address the comprehension of one's own physical and mental states so that perceptions of both premenstruation and menstruation become more positive. Findings also suggest that the family's understanding was associated with alleviation of premenstrual distress. This study suggests the need for education to help adolescent girls and their families manage premenstrual distress and increase awareness of the benefit of managing its associated symptoms.

Health-related quality of life in young adults in education, employment, or training: development of the Japanese version of Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales Young Adult Version.

PURPOSE: The purpose of the study is to develop a Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales Young Adult Version (PedsQL-YA-J) and determine the feasibility, reliability, and validity of the scales. METHODS: Translation equivalence and content validity were verified using back-translation and cognitive debriefing tests. A total of 428 young adults recruited from one university, two vocational schools, or five companies completed questionnaires. We determined questionnaire feasibility, internal consistency, and test-retest reliability; checked concurrent validity against the Center for Epidemiologic Studies Depression Scale (CES-D); determined convergent and discriminant validity with the Medical Outcome Study 36-item Short Form Health Survey (SF-36); described known-groups validity with regard to subjective symptoms, illness or injury requiring regular medical visits, and depression; and verified factorial validity. RESULTS: All scales were internally consistent (Cronbach's coefficient alpha = 0.77-0.86); test-retest reliability was acceptable (intraclass correlation coefficient = 0.57-0.69); and all scales were concurrently valid with depression (Pearson's correlation coefficient = 0.43-0.57). The scales convergent and discriminant validity with the SF-36 and CES-D were acceptable. Evaluation of known-groups validity confirmed that the Physical Functioning scale was sensitive for subjective symptoms, the Emotional Functioning scale for depression, and the Work/School Functioning scale for illness or injury requiring regular medical visits. Exploratory factor analysis found a six-factor structure consistent with the assumed structure (cumulative proportion = 57.0%). CONCLUSIONS: The PedsQL-YA-J is suitable for assessing health-related quality of life in young adults in education, employment, or training, and for clinical trials and epidemiological research.

Cancer-specific health-related quality of life in children with brain tumors.

PURPOSE: To understand the influence of disease and treatment on the health-related quality of life (HRQOL) of children with brain tumors, compared to the HRQOL of children with other cancers, from the viewpoints of children and parents. METHODS: A total of 133 children aged 5-18 years and 165 parents of children aged 2-18 completed questionnaires of the Pediatric Quality of Life Inventory Cancer Module (Pain and Hurt, Nausea, Procedural Anxiety, Treatment Anxiety, Worry, Cognitive Problems, Perceived Physical Appearance, and Communication scales); higher scores indicate a better HRQOL. The Cancer Module scores, weighted by age and treatment status, were compared to those obtained in a previous study of children with other cancers (mostly leukemia). RESULTS: The weighted mean scores for Pain and Hurt (effect size d = 0.26) and Nausea (d = 0.23) from child reports and the scores for Nausea (d = 0.28) from parent reports were higher for children with brain tumors than scores for children with other cancers. The scores for Procedural Anxiety (d = -0.22) and Treatment Anxiety (d = -0.32) from parent reports were lower for parents of children with brain tumors than the scores for parents of children with other cancers. The child-reported Pain and Hurt score of the Cancer Module was higher (d = 0.29) and in less agreement (intraclass correlation coefficient = 0.43) with scores from the Brain Tumor Module, indicating that assessments completed with the Cancer Module misesteem pain and hurt problems in children with brain tumors. CONCLUSIONS: The profiles of cancer-specific HRQOL in children with brain tumors differ from those of children with other cancers; we therefore suggest that these children receive specific psychological support.

The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention.

Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.