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Purpose This study aimed to assess psychometric properties of the Japanese version of the EQ-5D-Y (3 levels) with a focus on feasibility, reliability, and construct validity. Methods Respondents were recruited from the general populations of three cities in Japan. First, children and adolescents responded to the EQ-5D-Y and PedsQL by self-report. Parents were also asked to evaluate the health states of their children/adolescents using proxy versions of these questionnaires. Next, the EQ-5D-Y was mailed to their residence approximately 2 weeks later, and both children/adolescents and their parents responded to the questionnaire. Reliability was confirmed by self-report test–retest methods and a comparison of self-report responses with proxy responses. Spearman’s correlation coefficients were calculated between responses to the EQ-5D-Y and both responses to and scores of the PedsQL in order to assess construct validity. Results A total of 654 children/adolescents from aged 8 to 15 (median age: 11) responded to the questionnaires at both the first- and second-stage surveys. Test–retest agreement was sufficiently high and was influenced by age. Proxy test–retest results revealed that parents’ responses were more reliable compared to the self-report results. Some correlations (| r | > 0.3) between items of the EQ-5D-Y and PedsQL were found. Meanwhile, no correlations were found between proxy responses to the EQ-5D-Y and self-report responses to the PedsQL. Conclusions The EQ-5D-Y demonstrates reliability and validity among children/adolescents and their parents in Japan. Construct validity of the EQ-5D-Y by self-report was confirmed through comparisons with the PedsQL. Proxy responses to the EQ-5D-Y were more reliable compared to the self-report results, but construct validity was not confirmed in the proxy version.

PurposeThis study aimed to develop a Japanese value set for the EORTC QLU-C10D, a multi-attribute utility measure derived from the cancer-specific health-related quality-of-life (HRQL) questionnaire, the EORTC QLQ-C30. The QLU-C10D contains ten HRQL dimensions: physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems.MethodsQuota sampling of a Japanese online panel was used to achieve representativeness of the Japanese general population by sex and age (≥ 18 years). The valuation method was an online discrete choice experiment. Each participant considered 16 choice pairs, randomly assigned from 960 choice pairs. Each pair included two QLU-C10D health states and life expectancy. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Preference weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy.ResultsA total of 2809 eligible panel members consented, 2662/2809 (95%) completed at least one choice pair, and 2435/2662 (91%) completed all choice pairs. Within dimensions, preference weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Intermediate utility weights were associated with social functioning and nausea; the remaining symptoms and emotional functioning were associated with smaller utility decrements. The value of the worst health state was − 0.221, lower than that seen in most other existing QLU-C10D country-specific value sets.ConclusionsThe Japan-specific QLU-C10D value set is suitable for evaluating the cost and utility of oncology treatments for Japanese health technology assessment and decision-making.

Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice, has been observed in an iron-based superconductor, BaFe 2 (As 1− x P x ) 2 , over a wide range of phosphorus concentration, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides. Multiple transitions in an iron-pnictide Electron nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice, has been observed in the iron pnictide and copper oxide high-temperature superconductors, but whether it can exist above the structural transition temperature ( T s ) without an external driving force was not known. Kasahara et al . report magnetic torque measurements in the iron pnictide superconductor BaFe 2 (As 1– x P x ) 2 showing that the nematicity develops well above T s and persists to the nonmagnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides. The authors identify two distinct temperatures — one at T *, signifying a true nematic transition, and the other at T s (less than T *) — which they show is not a true phase transition, but rather a 'meta-nematic' transition. Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice 1 , 2 , has been observed in the iron pnictide 3 , 4 , 5 , 6 , 7 and copper oxide 8 , 9 , 10 , 11 high-temperature superconductors. Whether nematicity plays an equally important role in these two systems is highly controversial. In iron pnictides, the nematicity has usually been associated with the tetragonal-to-orthorhombic structural transition at temperature T s . Although recent experiments 3 , 4 , 5 , 6 , 7 have provided hints of nematicity, they were performed either in the low-temperature orthorhombic phase 3 , 5 or in the tetragonal phase under uniaxial strain 4 , 6 , 7 , both of which break the 90° rotational C 4 symmetry. Therefore, the question remains open whether the nematicity can exist above T s without an external driving force. Here we report magnetic torque measurements of the isovalent-doping system BaFe 2 (As 1− x P x ) 2 , showing that the nematicity develops well above T s and, moreover, persists to the non-magnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides 8 , 12 . By combining these results with synchrotron X-ray measurements, we identify two distinct temperatures—one at T *, signifying a true nematic transition, and the other at T s (< T *), which we show not to be a true phase transition, but rather what we refer to as a ‘meta-nematic transition’, in analogy to the well-known meta-magnetic transition in the theory of magnetism.

A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature ( T c ). To address this issue, FeSe is a key material, as it exhibits a unique pressure phase diagram involving non-magnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe have considerable overlap, how each order affects superconductivity remains perplexing. Here we construct the three-dimensional electronic phase diagram, temperature ( T ) against pressure ( P ) and isovalent S-substitution ( x ), for FeSe 1− x S x . By simultaneously tuning chemical and physical pressures, against which the chalcogen height shows a contrasting variation, we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended non-magnetic tetragonal phase emerges, where T c shows a striking enhancement. The completed phase diagram uncovers that high- T c superconductivity lies near both ends of the dome-shaped antiferromagnetic phase, whereas T c remains low near the nematic critical point.

Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0–11.6% after bone marrow or PBSC transplantation and 4.9–21.4% after umbilical cord blood transplantation, typically around 2–6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication.

In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09, P <0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48, P <0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively ( P <0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%, P =0.044; ganciclovir, 84% vs 58%, P =0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.

Optimal pre-hospital care for out-of-hospital cardiac arrest (OHCA) caused by respiratory disease may differ from that for OHCA associated with other aetiologies, especially with respect to respiratory management. We aimed to investigate whether pre-hospital advanced airway management (AAM) was associated with favourable outcomes after OHCA caused by intrinsic respiratory disease. This nationwide, population-based, propensity score-matched study of adult patients in Japan with OHCA due to respiratory disease from 1 January 2005 to 31 December 2012 compared patients with and without pre-hospital AAM. The primary outcome was neurologically favourable survival at one month after the OHCA. Of 49,534 eligible patients, 20,458 received pre-hospital AAM and 29,076 did not. In a propensity score-matched cohort (18,483 versus 18,483 patients), the odds of neurologically favourable survival were significantly lower for patients receiving pre-hospital AAM (0.6% versus 1.5%; odds ratio [OR] 0.42 [95% confidence interval {CI} 0.34 to 0.52]). The results from multivariable logistic regression analysis also showed that pre-hospital AAM was significantly associated with a decreased chance of neurologically favourable survival (adjusted OR 0.43 [95% CI 0.35 to 0.52]). Similar findings were observed for one-month survival and pre-hospital return of spontaneous circulation. In subgroup analyses, pre-hospital AAM was associated with poor neurological outcomes, regardless of the type of airway device used (laryngeal mask airway, adjusted OR 0.35 [95% CI 0.19 to 0.57]; oesophageal obturator airway, adjusted OR 0.44 [95% CI 0.35 to 0.55]; and endotracheal tube, adjusted OR 0.47 [95% CI 0.30 to 0.69]). In conclusion, pre-hospital AAM was associated with poor neurological outcome among patients with OHCA caused by intrinsic respiratory disease.

Purpose The Functional Assessment of Cancer Therapy General (FACT-G) questionnaire is frequently used to assess health-related quality of life (HRQOL) in cancer patients. However, data obtained using the FACT-G cannot be directly used to calculate quality-adjusted life years (QALYs). The newly developed FACT Eight Dimensions (FACT-8D) is a preference-based measure that generates health utilities scores from 9 of the 27 FACT-G items, representing eight HRQOL domains (Nausea, Pain, Fatigue, Sleep, Work, Worry, Sadness, Support from family/friends). This study aimed to create a Japanese FACT-8D value set. Methods A cross-sectional online survey of the Japanese general population recruited participants via a Japanese online panel, quota sampled by age (≥ 18 years) and sex. FACT-8D valuation data were collected with a discrete choice experiment. The valuation task required each participant to consider 16 pairs of hypothetical health states, randomly assigned per participant from 800 choice-sets. Preference weights were obtained from conditional logit models by dividing estimated HRQOL coefficients by the life duration coefficient. Results Data from 2320 participants were used to assess sample representativeness and estimate the Japanese value set. All preference weights other than Worry Level 2 were negative and increased in absolute terms in progressively higher levels of adverse HRQOL impact. The most influential domains for health utilities were Pain and Nausea, followed by Work problems. Fatigue, Sleep, Support, Sadness, and health Worry had moderate influences on health utilities. The lowest score, for the pit state [55555555], was − 0.60. This value is much lower than that of the EORTC QLU-C10D pit state [4444444444], -0.22. Health states were consistently scored higher in the USA, Australia and the UK than in Japan. Canadian health states are generally lower than for Japan, but not universally so. Conclusions We established the Japanese FACT-8D value set based on the internationally common protocol. The value set provides another option for quantifying health utilities for cancer outcomes. This contributes to improving the feasibility of deriving health utilities from the widely used FACT-G.

Background: We performed a cost-effectiveness analysis of trastuzumab plus chemotherapy for human epidermal growth factor type-2 (HER2)-positive advanced gastric cancer (GC) based on data obtained from the Trastuzumab for Gastric Cancer (ToGA) trial from a Japanese perspective. Methods: The following Japanese and Korean populations of the ToGA trial were analysed to obtain mean overall and progression-free survival times: (1) all HER2-positive populations, (2) immunohistochemical (IHC) 2+/fluorescence in situ hybridisation (FISH)+ or IHC 3+ populations, and (3) IHC 3+ only population. The effect of trastuzumab treatment on mean survival time was estimated by fitting a Weibull parametric function. Costs were calculated from the perspective of health-care payer. Neither costs nor outcomes were discounted because of short life expectancy. Results: In the base-case analysis, the incremental cost-effectiveness ratio was (1) JPY 12 million (€110 000) per quality-adjusted life year (QALY) gained and JPY 8.9 million (€81 000) per life-year gained (LYG) for all HER2-positive populations, (2) JPY 9.1 million (€83 000) per QALY gained and JPY 6.6 million (€60 000) per LYG for the IHC 2+/FISH+ or IHC 3+ population, and (3) JPY 6.1 million (€55 000) per QALY gained and JPY 4.3 million (€39 000) per LYG for the IHC 3+ population. Conclusion: Trastuzumab treatment for IHC 3+ populations is cost effective. Our analysis can find a cost-effective subgroup when advanced GC is treated by trastuzumab.

To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m 2 , Underweight, n =1791; 18.5⩽BMI<25, Normal, n =8444; 25⩽BMI<30, Overweight, n =1591; BMI⩾30, Obese, n =224. The median age was 45 years (range, 18–77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P =0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.