Family caregiving in dementia and its impact on quality of life and economic burden in Japan-web based survey.

Background: Dementia has become a growing health-care problem in the rapidly ageing Japanese population. This study assesses the impact of dementia on quality of life, economic burden, and productivity loss. Objective: The objective of this study was to assess the impact of dementia on the Quality of Life (QoL), economic burden, and productivity loss among families living with dementia. Methods: An online survey was conducted among families who lived with relatives with dementia. Demographic data and information about health condition and costs of long-term care and treatment were collected. Participants were asked to answer the EuroQol (EQ-5D-5L) questionnaire, Zarit Burden Interview (ZARIT-8), and Work Productivity and Activity Impairment Questionnaire (WPAI). Multivariate analyses were conducted to assess factors associated with burden by families living with dementia. Results: Six hundred and thirty-five participants completed the survey. Of these participants, 50.5% were primary caregivers. Overall, 78.7% of dementia patients suffered from Alzheimer, and 43.9% needed long-term care. Compared to non-primary caregivers, primary caregivers had lower health utility scores (0.896 vs 0.873; p = 0.02), higher burden of caregiving (ZARIT-8: 21.1 vs 24.5; p < 0.0001), and higher overall work impairment (40.2% vs 20.8%; p < 0.0001), absenteeism (15.3% vs 5.7%; p < 0.0001), and presenteeism-related impairment (33.2% vs 17.3%; p < 0.0001). Conclusion: Families living with dementia caring for a person with dementia experience increased burden. Health policies related to dementia need to be considered not only for patients, but also for their families living with dementia to improve their QoL.

Applied Machine Learning Method to Predict Children With ADHD Using Prefrontal Cortex Activity: A Multicenter Study in Japan.

Objective: To establish valid, objective biomarkers for ADHD using machine learning. Method: Machine learning was used to predict disorder severity from new brain function data, using a support vector machine (SVM). A multicenter approach was used to collect data for machine learning training, including behavioral and physiological indicators, age, and reverse Stroop task (RST) data from 108 children with ADHD and 108 typically developing (TD) children. Near-infrared spectroscopy (NIRS) was used to quantify change in prefrontal cortex oxygenated hemoglobin during RST. Verification data were from 62 children with ADHD and 37 TD children from six facilities in Japan. Results: The SVM general performance results showed sensitivity of 88.71%, specificity of 83.78%, and an overall discrimination rate of 86.25%. Conclusion: A SVM using an objective index from RST may be useful as an auxiliary biomarker for diagnosis for children with ADHD.

Association of inattention with slow-spindle density in sleep EEG of children with attention deficit-hyperactivity disorder.

OBJECTIVE: We evaluated the power of slow sleep spindles during sleep stage 2 to clarify their relationship with executive function, especially with attention, in children with attention deficit-hyperactivity disorder (ADHD). METHODS: Subjects were 21 children with ADHD and 18 aged-matched, typically developing children (TDC). ADHD subjects were divided into groups of only ADHD and ADHD + autism spectrum disorder (ASD). We employed the Continuous Performance Test (CPT) to measure attention. We focused on sleep spindle frequencies (12-14 Hz) in sleep stage 2 and performed a power spectral analysis using fast Fourier transform techniques and compared sleep spindles with the variability of reaction time in CPT. RESULTS: In the CPT, reaction variabilities in ADHD and ADHD + ASD significantly differed from those in TDC. Twelve-hertz spindles were mainly distributed in the frontal pole and frontal area and 14-Hz spindles in the central area. The ratio of 12-Hz frontal spindle power was higher in ADHD than in TDC, especially in ADHD + ASD. Significant correlation between the ratio of 12-Hz spindles and reaction time variability was observed. CONCLUSIONS: Twelve-hertz frontal spindle EEG activity may have positive associations with sustained attention function. Slow frontal spindles may be useful as a biomarker of inattention in children with ADHD.

Age-related differences in frontal lobe function in children with ADHD.

BACKGROUND: The neural correlates of executive function disorders are thought to be predominantly localized within the prefrontal cortex (PFC). However, no study to date has investigated changes in this system across different age groups in children with attention deficit hyperactivity disorder (ADHD). Thus, this study aimed to explore changes in PFC function in children with ADHD. METHODS: Study participants included typically developing (TD) children (n = 140) and children with ADHD (n = 67) of primary school age. Behavioral executive functions and their neural basis were evaluated between the TD children and children with ADHD and also across different age periods (younger and older children). To examine executive function, inhibitory control was assessed using the reverse Stroop task, and PFC near-infrared spectroscopic measurements were used to investigate the neural mechanisms involved. RESULTS: Both ADHD symptoms and the ability to inhibit color interference improved with age. Compared to TD children, children with ADHD demonstrated decreased activation of the right and middle PFC across all age groups. Interestingly, the left PFC appeared to play a compensatory role. CONCLUSION: Children with ADHD exhibited changes in PFC function that varied with age. Longitudinal studies are required to assess the potential of using PFC function as an early biomarker of ADHD.

Predictive factors of success in neurofeedback training for children with ADHD.

INTRODUCTION: Neurofeedback (NF) training aims the enhancement of self-regulation over brain activities. While it is largely recognized as an effective treatment for attention deficit hyperactivity disorder (ADHD), the existence of non-learners has also been reported. The present study explored pre-training assessment indices that could predict learners prior to NF training. METHODS: Twenty-two children with ADHD participated in slow cortical potential (SCP) NF training and completed pre- and post-training assessments. Participants were classified into learners or non-learners based on their progress in the SCP regulation, and pre-training indices that differentiate the two groups were examined by decision tree analysis. RESULTS AND DISCUSSION: The learner rate in NF training was 45.5%. Learners were predicted by pre-training cognitive and neurophysiological measures regarding Stroop tasks, which suggested relatively intact executive function as their characteristics. Given that NF training is not universally effective for children with ADHD, further studies are necessary to establish application criteria.

[Universal Health Coverage and Cancer Drugs - A Cost-Effectiveness Perspective].

Japanese health system has been evaluated to be the closest to the ideal Universal Health Coverage(UHC)in the world. "Ideal UHC" is to ensure that all people could obtain the health services they need without suffering any financial hardship. However, maintaining current healthcare system, under which all medications are covered, is getting difficult due to the aging society and the existence of high-price drugs such as anti-cancer agents. Approval of OPDIVO(nivolumab)has raised the national discussion in Japan because of the possibility that the use of OPDIVO might collapse overall healthcare system. Many countries that have public health insurance system like Japan have introduced Health Technology Assessment(HTA)for pricing and reimbursement decision. In the UK, The National Institute for Health and Care Excellence(NICE)is in charge of HTA and using health-economic data for reimbursement decisions. Japan has decided to implement HTA and the provisional phase has started this year. The use of health-economic data is different between Japan and UK. For instance, health-economic data is used only for pricing in Japan, although it is also used for reimbursement in the UK. HTA implementation in Japan has been criticized, saying that it might prohibit patients' access to medical treatments. However, the HTA is the solution of rising national burden of medical costs. It could benefit to sustainable UHC, and therefore, it could ensure patients' access to essential medicines.

Development and preclinical efficacy of novel transforming growth factor-ß1 short interfering RNAs for pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic devastating disease of unknown etiology. No therapy is currently available. A growing body of evidence supports the role of transforming growth factor (TGF)-ß1 as the major player in the pathogenesis of the disease. However, attempts to control its expression and to improve the outcome of pulmonary fibrosis have been disappointing. We tested the hypothesis that TGF-ß1 is the dominant factor in the acute and chronic phases of pulmonary fibrosis and developed short interfering (si)RNAs directed toward molecules implicated in the disease. This study developed novel sequences of siRNAs targeting the TGF-ß1 gene and evaluated their therapeutic efficacy in two models of pulmonary fibrosis: a model induced by bleomycin and a novel model of the disease developed spontaneously in mice overexpressing the full length of human TGF-ß1 in the lungs. Intrapulmonary delivery of aerosolized siRNAs of TGF-ß1 with sequences common to humans and rodents significantly inhibited bleomycin-induced pulmonary fibrosis in the acute and chronic phases of the disease and in a dose-dependent manner. Aerosolized human-specific siRNA also efficiently inhibited pulmonary fibrosis, improved lung function, and prolonged survival in human TGF-ß1 transgenic mice. Mice showed no off-target effects after intratracheal administration of siRNA. These results suggest the applicability of these novel siRNAs as tools for treating pulmonary fibrosis in humans.

Malignant myoepithelioma with a squamous epithelial component in the mammary gland of a cynomolgus monkey.

A solid mass arising from the mammary gland was found in a 7-year-old female cynomolgus monkey. Histologically, the mass consisted of 2 components: spindle-shaped or ovoid sarcomatous cells and squamous epithelial cells. Metastatic nodules noted in the lung, liver and the gallbladder had the same histological features as the mammary mass. Immunohistochemistry revealed that the sarcomatous cells were positive for alpha-smooth muscle actin (alpha-SMA), vimentin, calponin, S-100 protein, epithelial membranous antigen (EMA), cytokeratin (large spectrum) and cytokeratin 14 (CK 14) in the cytoplasm, and p53, erbB-2 and progesterone receptor in the nuclei, but negative for desmin and estrogen receptor. The squamous epithelial cells were positive for EMA, cytokeratin (large spectrum) and CK 14, but negative for the rest. Both sarcomatous and squamous epithelial components were negative for glial fibrillary acidic protein (GFAP). Based on histological and immunohistochemical features, the present case was diagnosed as a malignant myoepithelioma with a squamous epithelial component in the mammary gland with distant metastases.