Publications by authors named "Naomi Hasegawa"

33 Publications

A dissemination and education programme to improve the clinical behaviours of psychiatrists in accordance with treatment guidelines for schizophrenia and major depressive disorders: the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project.

BJPsych Open 2022 Apr 21;8(3):e83. Epub 2022 Apr 21.

Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University School of Medicine, Japan.

Background: Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists.

Aims: The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes.

Method: A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme.

Results: All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending.

Conclusions: All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.
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http://dx.doi.org/10.1192/bjo.2022.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059732PMC
April 2022

Relationship between autistic traits and social functioning in healthy individuals.

Neuropsychopharmacol Rep 2022 Apr 1. Epub 2022 Apr 1.

Department of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan.

Aim: Social functioning is influenced by various factors. Autistic traits could be one of the factors that affect social functioning.

Methods: In the present study, the relationship between autistic traits and social functioning among 755 healthy individuals was analyzed. Autistic traits were assessed with the autism-spectrum quotient. Social functioning was assessed by the social functioning scale and the social activity assessment.

Results: The Autism-Spectrum Quotient total score was significantly negatively correlated with the social functioning scale total and all subscales of the social functioning scale. All subscales of the Autism-Spectrum Quotient except attention to detail were significantly negatively correlated with the social functioning scale total score. However, the Autism-Spectrum Quotient was not correlated with the social activity assessment, which indicates labor functioning.

Conclusion: Autistic traits of healthy individuals had a negative impact on situations in real life through social functioning for daily life-sustaining. The effect was not enough to affect labor functioning as indicated by working hours in healthy individuals. These findings should also be examined in individuals with autism spectrum disorder in future studies.
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http://dx.doi.org/10.1002/npr2.12249DOI Listing
April 2022

Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry.

Neuropsychopharmacol Rep 2022 Mar 10. Epub 2022 Mar 10.

Department of Psychiatry, Tohoku University hospital, Miyagi, Japan.

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.
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http://dx.doi.org/10.1002/npr2.12245DOI Listing
March 2022

The characteristics of patients receiving psychotropic pro re nata medication at discharge for the treatment of schizophrenia and major depressive disorder: A nationwide survey from the EGUIDE project.

Asian J Psychiatr 2022 Mar 13;69:103007. Epub 2022 Jan 13.

Department of NeuroPsychiatry, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8524, Japan.

Background: Although several guidelines indicate that daily pharmacotherapy is an important part of the treatment of schizophrenia and major depressive disorder, there are few reports regarding pro re nata (PRN) prescriptions. The purpose of this study is to clarify the characteristics of patients receiving psychotropic PRN prescription for the treatment of schizophrenia and major depressive disorder.

Method: We used data from 'the effectiveness of guideline for dissemination and education in psychiatric treatment' (EGUIDE) project to evaluate the presence or absence of psychotropic PRN prescription at the time of discharge, the age and sex of patients receiving PRN prescription for each diagnosis, and the association between PRN prescription and regular daily psychotropics.

Results: The psychotropic PRN prescription ratio was 29.9% among 2617 patients with schizophrenia and 31.1% among 1248 patients with major depressive disorder at discharge. In schizophrenia, the psychotropic PRN prescription ratio was 21.6% for patients aged 65 years or older, which was lower than that of all other age groups. In major depressive disorder, the psychotropic PRN prescription ratio was 34.2% for female patients, which was significantly higher than that for male patients (25.5%). In schizophrenia, there was an association between psychotropic PRN prescription and regular use of multiple psychotropic medications.

Conclusions: Psychotropic PRN prescription was less common in elderly patients with schizophrenia and more common in female patients with major depressive disorder. In schizophrenia, psychotropic PRN prescription led to polypharmacy of psychotropics. Further studies are needed to accumulate evidence and to provide education on appropriate PRN prescriptions.
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http://dx.doi.org/10.1016/j.ajp.2022.103007DOI Listing
March 2022

Association Study Between White Matter Microstructure and Intelligence Decline in Schizophrenia.

Clin EEG Neurosci 2021 Dec 10:15500594211063314. Epub 2021 Dec 10.

26361National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.

Patients with schizophrenia can exhibit intelligence decline, which is an important element of cognitive impairment. Previous magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have altered gray matter structures and functional connectivity associated with intelligence decline defined by a difference between premorbid and current intelligence quotients (IQs). However, it has remained unclear whether white matter microstructures are related to intelligence decline. In the present study, the indices of diffusion tensor imaging (DTI) obtained from 138 patients with schizophrenia and 554 healthy controls were analyzed. The patients were classified into three subgroups based on intelligence decline: deteriorated (94 patients), preserved (42 patients), and compromised IQ (2 patients) groups. Given that the DTI of each subject was acquired using either one of two different MRI scanners, we analyzed DTI indices separately for each scanner group. In the comparison between the deteriorated IQ group and the healthy controls, differences in some DTI indices were noted in three regions of interest irrespective of the MRI scanners, whereas differences in only one region of interest were noted between the preserved IQ group and the healthy controls. However, the comparisons between the deteriorated and preserved IQ groups did not show any reproducible differences. Together with the previous findings, it is thought that gray matter structures and functional connectivity are more promising as markers of intelligence decline in schizophrenia than white matter microstructures.
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http://dx.doi.org/10.1177/15500594211063314DOI Listing
December 2021

Hypnotic medication use among inpatients with schizophrenia and major depressive disorder: results of a nationwide study.

Sleep Med 2022 01 22;89:23-30. Epub 2021 Nov 22.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan. Electronic address:

Study Objectives: To investigate the proportion of inpatients with schizophrenia and major depressive disorder prescribed hypnotic medication, and the association between such medication and the use of other antipsychotic agents.

Methods: This was a nationwide cross-sectional study performed as part of the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment' (EGUIDE) project. Data from 2146 inpatients with schizophrenia and 1031 inpatients with major depressive disorder were analyzed. All types and dosages of psychotropic drugs were recorded and the data at the time of discharge were analyzed. Associations between the use of hypnotic medication and other antipsychotic agents were evaluated using multivariate logistic regression analyses.

Results: The proportions of schizophrenia patients who were prescribed any and two or more hypnotic agents were 55.7% and 17.6%, respectively, and the corresponding proportions for patients with major depressive disorder were 63.6% and 22.6%, respectively. In schizophrenia patients, multivariate logistic regression analyses showed that two or more antipsychotics, anticholinergic drugs, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. In patients with major depressive disorder, multivariate logistic regression analyses revealed that two or more antidepressants, two or more antipsychotics, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent.

Conclusions: Prescription of hypnotic agents was found to be highly frequent among inpatients with psychiatric disorders. Prescription of two or more main antipsychotic agents was commonly associated with the use of hypnotic medication for both schizophrenia and major depressive disorder.
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http://dx.doi.org/10.1016/j.sleep.2021.11.005DOI Listing
January 2022

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study.

Neuropsychopharmacol Rep 2022 03 2;42(1):3-9. Epub 2021 Dec 2.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine.

Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study.

Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r  = 0.531, P = 1.032 × 10 ). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS.

Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families.
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http://dx.doi.org/10.1002/npr2.12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919118PMC
March 2022

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling.

Elife 2021 11 9;10. Epub 2021 Nov 9.

Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States.

Background: Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. We have developed a mechanistic mathematical model for better understanding these factors and their relations in order to predict treatment outcome and optimize personal treatment strategies.

Methods: Here, we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (), tumor-immune infiltration (), and immunotherapy-mediated amplification of anti-tumor response (). The model was calibrated by fitting it to a compiled clinical tumor response dataset (n = 189 patients) obtained from published anti-PD-1 and anti-PD-L1 clinical trials, and then validated on an additional validation cohort (n = 64 patients) obtained from our in-house clinical trials.

Results: The derived parameters and were both significantly different between responding versus nonresponding patients. Of note, our model appropriately classified response in 81.4% of patients by using only tumor volume measurements and within 2 months of treatment initiation in a retrospective analysis. The model reliably predicted clinical response to the PD-1/PD-L1 class of checkpoint inhibitors across multiple solid malignant tumor types. Comparison of model parameters to immunohistochemical measurement of PD-L1 and CD8+ T cells confirmed robust relationships between model parameters and their underlying biology.

Conclusions: These results have demonstrated reliable methods to inform model parameters directly from biopsy samples, which are conveniently obtainable as early as the start of treatment. Together, these suggest that the model parameters may serve as early and robust biomarkers of the efficacy of checkpoint inhibitor therapy on an individualized per-patient basis.

Funding: We gratefully acknowledge support from the Andrew Sabin Family Fellowship, Center for Radiation Oncology Research, Sheikh Ahmed Center for Pancreatic Cancer Research, GE Healthcare, Philips Healthcare, and institutional funds from the University of Texas M.D. Anderson Cancer Center. We have also received Cancer Center Support Grants from the National Cancer Institute (P30CA016672 to the University of Texas M.D. Anderson Cancer Center and P30CA072720 the Rutgers Cancer Institute of New Jersey). This research has also been supported in part by grants from the National Science Foundation Grant DMS-1930583 (ZW, VC), the National Institutes of Health (NIH) 1R01CA253865 (ZW, VC), 1U01CA196403 (ZW, VC), 1U01CA213759 (ZW, VC), 1R01CA226537 (ZW, RP, WA, VC), 1R01CA222007 (ZW, VC), U54CA210181 (ZW, VC), and the University of Texas System STARS Award (VC). BC acknowledges support through the SER Cymru II Programme, funded by the European Commission through the Horizon 2020 Marie Skłodowska-Curie Actions (MSCA) COFUND scheme and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF). EK has also received support from the Project Purple, NIH (U54CA210181, U01CA200468, and U01CA196403), and the Pancreatic Cancer Action Network (16-65-SING). MF was supported through NIH/NCI center grant U54CA210181, R01CA222959, DoD Breast Cancer Research Breakthrough Level IV Award W81XWH-17-1-0389, and the Ernest Cockrell Jr. Presidential Distinguished Chair at Houston Methodist Research Institute. RP and WA received serial research awards from AngelWorks, the Gillson-Longenbaugh Foundation, and the Marcus Foundation. This work was also supported in part by grants from the National Cancer Institute to SHC (R01CA109322, R01CA127483, R01CA208703, and U54CA210181 CITO pilot grant) and to PYP (R01CA140243, R01CA188610, and U54CA210181 CITO pilot grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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http://dx.doi.org/10.7554/eLife.70130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629426PMC
November 2021

Characteristics of discharge prescriptions for patients with schizophrenia or major depressive disorder: Real-world evidence from the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project.

Asian J Psychiatr 2021 Sep 15;63:102744. Epub 2021 Jul 15.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists.

Methods: We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018.

Results: The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants.

Conclusions: Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.
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http://dx.doi.org/10.1016/j.ajp.2021.102744DOI Listing
September 2021

Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study.

Neuropsychopharmacol Rep 2021 06 11;41(2):199-206. Epub 2021 Mar 11.

Department of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan.

Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD).

Methods: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared.

Results: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group.

Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.
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http://dx.doi.org/10.1002/npr2.12173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340832PMC
June 2021

Effects of age and sex on eye movement characteristics.

Neuropsychopharmacol Rep 2021 06 21;41(2):152-158. Epub 2021 Feb 21.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.

Abnormal eye movements are often associated with psychiatric disorders. Eye movements are sensorimotor functions of the brain, and aging and sex would affect their characteristics. A precise understanding of normal eye movements is required to distinguish disease-related abnormalities from natural differences associated with aging or sex. To date, there is no multicohort study examining age-related dependency and sex effects of eye movements in healthy, normal individuals using large samples to ensure the robustness and reproducibility of the results. In this study, we aimed to provide findings showing the impact of age and sex on eye movement measures. The present study used eye movement measures of more than seven hundred healthy individuals from three large independent cohorts. We herein evaluated eye movement measures quantified by using a set of standard eye movement tests that have been utilized for the examination of patients with schizophrenia. We assessed the statistical significance of the effects of age and sex and its reproducibility across cohorts. We found that 4-18 out of 35 eye movement measures were significantly correlated with age, depending on the cohort, and that 10 of those, which are related to the fixation and motor control of smooth pursuit and saccades, showed high reproducibility. On the other hand, the effects of sex, if any, were less reproducible. The present results suggest that we should take age into account when we evaluate abnormalities in eye movements.
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http://dx.doi.org/10.1002/npr2.12163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340818PMC
June 2021

Relationship between white matter microstructure and work hours.

Neurosci Lett 2021 01 18;740:135428. Epub 2020 Oct 18.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8553, Japan; Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:

Human social activities are realized by a synergy of neuronal activity over various regions of the brain, which is supported by their connectivity. In the present study, we examined associations between social activities, represented by work hours, and brain connectivity as quantified using diffusion tensor imaging (DTI). In 483 healthy participants, DTI analysis was performed using 3 T magnetic resonance imaging, and work hours were calculated, considering hours of paid employment (the "Work for Pay" category), hours of housework (the "Work at Home" category), and hours of school-related study (the "Student" category). The correlations between each class of work time and DTI indices were analyzed. The mean diffusivity (MD) values of the anterior limb of the internal capsule (ALIC) and the superior fronto-occipital fasciculus (SFO) were negatively correlated with total work hours (ALIC: r = -0.192, p =  2.3 × 10; SFO: r = -0.161, p =  3.8 × 10). We also found that the MD values of the ALIC and the SFO were correlated with work hours in the Work for Pay category (ALIC: r = -0.211, p =  3.2 × 10; SFO: r = -0.163, p =  3.4 × 10) but not with those in the Work at Home category or the Student category. These results suggest that social activity is associated with the white matter microstructure of the ALIC and the SFO. The main difference between "Work for Pay" and the other two social activities appears to be the type of motivation-for example, external versus internal. Therefore, the white matter microstructure of the ALIC and SFO may be related to externally motivated social activities.
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http://dx.doi.org/10.1016/j.neulet.2020.135428DOI Listing
January 2021

Intracellular Delivery of Adamantane-Tagged Small Molecule, Proteins, and Liposomes Using an Octaarginine-Conjugated β-Cyclodextrin.

ACS Appl Bio Mater 2020 Aug 28;3(8):4902-4911. Epub 2020 May 28.

Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan.

Herein, we demonstrate a convenient technique for the intracellular delivery of proteins and liposomes based on supramolecular host-guest chemistry. First, we prepared the R8-CD carrier molecule, which is a β-cyclodextrin derivative bearing an octaarginine (R8) chain, as a cell-penetrating peptide, at the primary hydroxyl group. The surface amino groups of proteins (GFP, β-gal, and IgG) were then partly modified with adamantane (Ad) tags using 1-Ad-carboxylic acid -hydroxysuccinimide ester (Ad-NHS). These Ad-tagged proteins were effectively delivered into HeLa cells though supramolecular host-guest interactions with R8-CD. A 100 nm sized liposome bearing Ad-tags on its surface was also delivered into these cells by the action of R8-CD. The present method does not require any genetic manipulation, and only easy chemical modification processes are used to facilitate intracellular delivery; therefore, we believe that the present method is applicable to a variety of bioengineering processes, such as protein-based therapeutics, cellular reprogramming, and genome-editing, among others.
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http://dx.doi.org/10.1021/acsabm.0c00421DOI Listing
August 2020

Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project.

Neuropsychopharmacol Rep 2020 09 30;40(3):281-286. Epub 2020 Jun 30.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Background: Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia.

Methods: A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs.

Results: Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%).

Conclusions: In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.
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http://dx.doi.org/10.1002/npr2.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722678PMC
September 2020

Core services of intensive case management for people with mental illness: A network analysis.

Int J Soc Psychiatry 2019 11 8;65(7-8):621-630. Epub 2019 Aug 8.

1 Department of Community Mental Health and Law, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.

Background: In intensive case management (ICM), users receive a wide variety of services of varying content, which makes it difficult to understand the global features of ICM programs.

Aims: The aim of this study was to examine the features of ICM programs using network analysis.

Methods: A total of 233 ICM users in two Japanese medical institutions were recruited to participate. All received services were recorded for 2 months. In the network analysis, nodes represented types of ICM services and edges between two nodes depicted when over 5% of participants received both types of services.

Results: We found high centrality values for 'H5. Hospital-based counseling', 'O13. Outreach support for mental health medications', 'H13. Hospital-based support for mental health medication', 'T5. Counseling via telecommunication', 'H3. Hospital-based coordination of services in the medical institution' and 'T2. Coordination of services with other institutions via telecommunication'. These results indicated that these services were associated with various other types of services. Social functioning was related to 'O13. Outreach support for mental health medication', whereas need for ICM was related to 'H13. Hospital-based support for mental health medications', 'T5. Counseling via telecommunication' and 'T2. Coordination of services with other institutions via telecommunication'.

Conclusion: Based on these findings, we speculated that there are at least five types of core services in ICM: regular face-to-face contact, outreach services, hospital-based services, easy contacts and coordination. These findings clarified the features of ICM programs, which may help improve the understanding of case managers' practice.
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http://dx.doi.org/10.1177/0020764019867346DOI Listing
November 2019

Development and evaluation of Intensive Case Management Screening Sheet in the Japanese population.

Int J Ment Health Syst 2019 5;13:22. Epub 2019 Apr 5.

1Department of Community Mental Health and Law, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), 4-1-1, Ogawahigashi, Kodaira, Tokyo Japan.

Background: In Japan, the mental health system has been shifting from hospitalization-based to community-based care; some organizations have gradually begun providing intensive case management (ICM) services. We developed an Intensive Case Management Screening Sheet (ICMSS) to screen for the need for ICM in people with mental illness.

Methods: The aim of this study was to examine the psychometric properties and discriminative ability of ICMSS. Subjects consisted of 911 people with mental illness. The ICMSS score was rated by a professional such as a nurse, social worker, or occupational therapist.

Results: Exploratory factor analysis showed a one-factor structure with 14 items. The factor structure was supported by confirmatory factor analysis (comparative fit index, 0.98; Tucker-Lewis index, 0.97; root mean square error test of close fit, 0.05). In the receiver operating characteristic analysis for discriminating between users and non-users of ICM services, the area under the curve (AUC) for ICMSS was significantly larger than for Global Assessment of Functioning and Personal and Social Performance Scale, indicating better discriminative ability. However, the AUC for ICMSS was moderate. Thus, we suggest that the need for ICM services is determined by quantitative assessment (i.e., ICMSS) and clinical judgment.

Conclusion: ICMSS is a brief tool for mental health professionals that will be useful in routine clinical practice. We expect that ICMSS will be used as a measure that reflects the views of professionals from various disciplines in Japanese institutions.
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http://dx.doi.org/10.1186/s13033-019-0278-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449981PMC
April 2019

Single-cell bioluminescence imaging of deep tissue in freely moving animals.

Science 2018 02;359(6378):935-939

Laboratory for Cell Function and Dynamics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.

Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals. Single tumorigenic cells trapped in the mouse lung vasculature could be visualized. In the mouse brain, genetic labeling with neural activity sensors allowed tracking of small clusters of hippocampal neurons activated by novel environments. In a marmoset, we recorded video-rate bioluminescence from neurons in the striatum, a deep brain area, for more than 1 year. AkaBLI is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.
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http://dx.doi.org/10.1126/science.aaq1067DOI Listing
February 2018

A new method for quantifying the performance of EEG blind source separation algorithms by referencing a simultaneously recorded ECoG signal.

Neural Netw 2017 Sep 29;93:1-6. Epub 2017 Jan 29.

Laboratory for Adaptive Intelligence, BSI, RIKEN, Saitama, Japan.

Blind source separation (BSS) algorithms extract neural signals from electroencephalography (EEG) data. However, it is difficult to quantify source separation performance because there is no criterion to dissociate neural signals and noise in EEG signals. This study develops a method for evaluating BSS performance. The idea is neural signals in EEG can be estimated by comparison with simultaneously measured electrocorticography (ECoG). Because the ECoG electrodes cover the majority of the lateral cortical surface and should capture most of the original neural sources in the EEG signals. We measured real EEG and ECoG data and developed an algorithm for evaluating BSS performance. First, EEG signals are separated into EEG components using the BSS algorithm. Second, the EEG components are ranked using the correlation coefficients of the ECoG regression and the components are grouped into subsets based on their ranks. Third, canonical correlation analysis estimates how much information is shared between the subsets of the EEG components and the ECoG signals. We used our algorithm to compare the performance of BSS algorithms (PCA, AMUSE, SOBI, JADE, fastICA) via the EEG and ECoG data of anesthetized nonhuman primates. The results (Best case >JADE = fastICA >AMUSE = SOBI ≥ PCA >random separation) were common to the two subjects. To encourage the further development of better BSS algorithms, our EEG and ECoG data are available on our Web site (http://neurotycho.org/) as a common testing platform.
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http://dx.doi.org/10.1016/j.neunet.2017.01.005DOI Listing
September 2017

Large-scale information flow in conscious and unconscious states: an ECoG study in monkeys.

PLoS One 2013 15;8(11):e80845. Epub 2013 Nov 15.

Laboratory for Adaptive Intelligence, Brain Science Institute, RIKEN, Saitama, Japan.

Consciousness is an emergent property of the complex brain network. In order to understand how consciousness is constructed, neural interactions within this network must be elucidated. Previous studies have shown that specific neural interactions between the thalamus and frontoparietal cortices; frontal and parietal cortices; and parietal and temporal cortices are correlated with levels of consciousness. However, due to technical limitations, the network underlying consciousness has not been investigated in terms of large-scale interactions with high temporal and spectral resolution. In this study, we recorded neural activity with dense electrocorticogram (ECoG) arrays and used the spectral Granger causality to generate a more comprehensive network that relates to consciousness in monkeys. We found that neural interactions were significantly different between conscious and unconscious states in all combinations of cortical region pairs. Furthermore, the difference in neural interactions between conscious and unconscious states could be represented in 4 frequency-specific large-scale networks with unique interaction patterns: 2 networks were related to consciousness and showed peaks in alpha and beta bands, while the other 2 networks were related to unconsciousness and showed peaks in theta and gamma bands. Moreover, networks in the unconscious state were shared amongst 3 different unconscious conditions, which were induced either by ketamine and medetomidine, propofol, or sleep. Our results provide a novel picture that the difference between conscious and unconscious states is characterized by a switch in frequency-specific modes of large-scale communications across the entire cortex, rather than the cessation of interactions between specific cortical regions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080845PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829858PMC
August 2014

[Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].

Jpn J Antibiot 2013 Jun;66(3):141-58

Clinical Safety & PMS Unit, Development & Medical Affairs Div., GlaxoSmithKline K. K.

As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, < or =0.06microg/mL for penicillin susceptible S. pneumoniae (PSSP) without any change, 0.5-1 microg/mL for penicillin intermediate resistant S. pneumoniae (PISP) with a twofold change and 1 microg/mL for PRSP with no change. The MIC90s of CVA/AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial activity intended for pediatric patients with otitis media or other infections, there was no significant change in antibacterial activity of CVA/AMPC (1: 14).
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June 2013

Spontaneous synchronization of arm motion between Japanese macaques.

Sci Rep 2013 28;3:1151. Epub 2013 Jan 28.

Laboratory for Adaptive Intelligence, Brain Science Institute , RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Humans show spontaneous synchronization of movements during social interactions; this coordination has been shown to facilitate smooth communication. Although human studies exploring spontaneous synchronization are increasing in number, little is known about this phenomenon in other species. In this study, we examined spontaneous behavioural synchronization between monkeys in a laboratory setting. Synchronization was quantified by changes in button-pressing behaviour while pairs of monkeys were facing one another. Synchronization between the monkeys was duly observed and it was participant-partner dependent. Further tests confirmed that the speed of button pressing changed to harmonic or sub-harmonic levels in relation to the partner's speed. In addition, the visual information from the partner induced a higher degree of synchronization than auditory information. This study establishes advanced tasks for testing social coordination in monkeys, and illustrates ways in which monkeys coordinate their actions to establish synchronization.
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http://dx.doi.org/10.1038/srep01151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556593PMC
July 2013

Spontaneous synchronization of arm motion between Japanese macaques.

Sci Rep 2013 28;3:1151. Epub 2013 Jan 28.

Laboratory for Adaptive Intelligence, Brain Science Institute , RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Humans show spontaneous synchronization of movements during social interactions; this coordination has been shown to facilitate smooth communication. Although human studies exploring spontaneous synchronization are increasing in number, little is known about this phenomenon in other species. In this study, we examined spontaneous behavioural synchronization between monkeys in a laboratory setting. Synchronization was quantified by changes in button-pressing behaviour while pairs of monkeys were facing one another. Synchronization between the monkeys was duly observed and it was participant-partner dependent. Further tests confirmed that the speed of button pressing changed to harmonic or sub-harmonic levels in relation to the partner's speed. In addition, the visual information from the partner induced a higher degree of synchronization than auditory information. This study establishes advanced tasks for testing social coordination in monkeys, and illustrates ways in which monkeys coordinate their actions to establish synchronization.
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http://dx.doi.org/10.1038/srep01151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556593PMC
July 2013

Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1.

J Biol Chem 2010 Aug 7;285(33):25185-95. Epub 2010 Jun 7.

Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.

The process by which the human immunodeficiency virus type 1 (HIV-1) conical core dissociates is called uncoating, but not much is known about this process. Here, we show that the uncoating process requires the interaction of the capsid (CA) protein with the peptidyl-prolyl isomerase Pin1 that specifically recognizes the phosphorylated serine/threonine residue followed by proline. We found that the HIV-1 core is composed of some isoforms of the CA protein with different isoelectric points, and one isoform is preferentially phosphorylated in the Ser(16)-Pro(17) motif. The mutant virus S16A/P17A shows a severely attenuated HIV-1 replication and an impaired reverse transcription. The S16A/P17A change increased the amount of particulate CA cores in the cytosol of target cells and correlated with the restriction of HIV-1 infection. Glutathione S-transferase pulldown assays demonstrated a direct interaction between Pin1 and the HIV-1 core via the Ser(16)-Pro(17) motif. Suppression of Pin1 expression by RNA interference in a target cell results in an attenuated HIV-1 replication and increases the amount of particulate CA cores in the cytosol of target cells. Furthermore, heat-inactivated, inhibitor-treated, or W34A/K63A Pin1 causes an attenuated in vitro uncoating of the HIV-1 core. The Pin1-dependent uncoating is inhibited by antisera raised against a CA peptide phosphorylated at Ser(16) or treatment of the HIV-1 core with alkaline phosphatase. These findings provide insights into this obscure uncoating process in the HIV-1 life cycle and a new cellular target for HIV-1 drug development.
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http://dx.doi.org/10.1074/jbc.M110.114256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919081PMC
August 2010

[Effects of processing and cooking on the levels of pesticide residues in soybean samples].

Shokuhin Eiseigaku Zasshi 2008 Jun;49(3):160-7

Residue Analysis Laboratory II, The Institute Environmental Toxicology, Ibaraki, Japan.

The effects of processing and cooking on the levels of pesticide residues in soybean samples were investigated for 14 pesticides in pre-harvest samples. On soaking, the transfer ratios (%, total pesticide residue amount in product/that in soybean) of soaked soybean were greater than 60% for most of the pesticides investigated. The transfer ratio of soymilk ranged from 37% to 92%, and that of tofu ranged from 7% to 63%. The processing factor (Pf, the concentration (mg/kg) of pesticide in product/that in soybean) of tofu ranged from 0.026 to 0.28. These values varied among pesticides. There was a high correlation between the log P(ow) and the transfer ratio of tofu. The test described here should be useful to obtain the transfer ratios of pesticide residues in processing and/or cooking steps.
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http://dx.doi.org/10.3358/shokueishi.49.160DOI Listing
June 2008

[Effects of processing and cooking on the levels of pesticide residues in wheat samples].

Shokuhin Eiseigaku Zasshi 2008 Jun;49(3):150-9

Residue Analysis Laboratory II, The Institute of Environmental Toxicology, Ibaraki, Japan.

The effects of processing and cooking on the levels of pesticide residues in wheat samples were investigated for 13 pesticides in pre-harvest (Pre, 9 pesticides) and post-harvest (Post, 6 pesticides) samples. In the milling process, the transfer ratios (%, total pesticide residue amount in product/that in wheat grain) of wheat bran were greater than 70% and 80% for pre-harvest and post-harvest samples, respectively. The transfer ratios of flour ranged from 1.7% to 23% (Pre) and 4.0% to 11% (Post). There was no significant difference in transfer ratio among the pesticides investigated. The processing factors (Pf, the concentration (mg/kg) of pesticide in product/that in the wheat grain) of flour ranged from 0.030 to 0.40 (Pre) and 0.069 to 0.18 (Post). The values in pre-harvest samples were higher than those in post-harvest samples. Investigation of changes of pesticide residues during processing and/or cooking is useful not only to establish MRLs, but also to recognize actual levels of pesticide residues in food.
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http://dx.doi.org/10.3358/shokueishi.49.150DOI Listing
June 2008

[Effects of processing and cooking on the levels of pesticide residues in rice samples].

Shokuhin Eiseigaku Zasshi 2008 Jun;49(3):141-9

Residue Analysis Laboratory II, The Institute of Environmental Toxicology, Ibaraki, Japan.

The effects of processing and cooking on the levels of pesticide residues in rice samples were investigated for 11 pesticides in pre-harvest (9 pesticides) and post-harvest (4 pesticides) samples. In the polishing process, the transfer ratio (%, total pesticide residue amount in product/that in brown rice) of rice bran ranged from 40% to 106%, and the transfer ratio of polished rice ranged from 9% to 65% in pre-harvest samples. These values varied from pesticide to pesticide. The processing factor (the concentration (mg/kg) of pesticide in product/that in the brown rice) of polished rice ranged from 0.11 to 0.73. The loss of pesticides during processing and/or cooking did not correlate to any single physical or chemical property. Investigation of changes of pesticide residues during processing and/or cooking is useful not only to establish MRLs, but also to recognize actual levels of pesticide residues in food.
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http://dx.doi.org/10.3358/shokueishi.49.141DOI Listing
June 2008

Mechanisms for modulation of mouse gastrointestinal motility by proteinase-activated receptor (PAR)-1 and -2 in vitro.

Life Sci 2006 Jan 26;78(9):950-7. Epub 2005 Sep 26.

Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.

Proteinase-activated receptor (PAR)-1 or -2 modulates gastrointestinal transit in vivo. To clarify the underlying mechanisms, we characterized contraction/relaxation caused by TFLLR-NH2 and SLIGRL-NH2, PAR-1- and -2-activating peptides, respectively, in gastric and small intestinal (duodenal, jejunal and ileal) smooth muscle isolated from wild-type and PAR-2-knockout mice. Either SLIGRL-NH2 or TFLLR-NH2 caused both relaxation and contraction in the gastrointestinal preparations from wild-type animals. Apamin, a K+ channel inhibitor, tended to enhance the peptide-evoked contraction in some of the gastrointestinal preparations, whereas it inhibited relaxation responses to either peptide completely in the stomach, but only partially in the small intestine. Indomethacin reduced the contraction caused by SLIGRL-NH2 or TFLLR-NH2 in both gastric and ileal preparations, but unaffected apamin-insensitive relaxant effect of either peptide in ileal preparations. Repeated treatment with capsaicin suppressed the contractile effect of either peptide in the stomach, but not clearly in the ileum, whereas it enhanced the apamin-insensitive relaxant effect in ileal preparations. In any gastrointestinal preparations from PAR-2-knockout mice, SLIGRL-NH2 produced no responses. Thus, the inhibitory component in tension modulation by PAR-1 and -2 involves both apamin-sensitive and -insensitive mechanisms in the small intestine, but is predominantly attributable to the former mechanism in the stomach. The excitatory component in the PAR-1 and -2 modulation may be mediated, in part, by activation of capsaicin-sensitive sensory nerves and/or endogenous prostaglandin formation. Our study thus clarifies the multiple mechanisms for gastrointestinal motility modulation by PAR-1 and -2, and also provides ultimate evidence for involvement of PAR-2.
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http://dx.doi.org/10.1016/j.lfs.2005.06.035DOI Listing
January 2006

Health-related quality of life (HRQOL) in Japanese osteoporotic patients and its improvement by elcatonin treatment.

J Bone Miner Metab 2005 ;23(2):167-73

Department of Orthopedic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.

Health-related quality of life (HRQOL; "QOL" hereafter) was evaluated in Japanese osteoporotic patients using three questionnaires; the SF-36 (MOS 36-Item Short-Form Health Survey; generic, profile-type), the EQ-5D (Euro Qol-5 Dimensions; generic, preference-based), and the JOQOL (Japanese Osteoporosis Quality of Life 1999; disease-targeted). The eight subscales and two summary scores of the SF-36 were impaired in these patients even after correction for age and sex. The scores on the EQ-5D and JOQOL correlated well with the subscales of the SF-36 that represent the physical aspects of physical function and bodily pain, which suggests that physical aspects are important determinants of overall QOL status in osteoporotic patients. Although the QOL scores did not correlate with bone mineral density, they were markedly influenced by the presence of vertebral fractures. In particular, the presence of two or more vertebral fractures greatly decreased the QOL scores. We then evaluated the QOL scores before and after treatment. The patients were either given calcium supplementation alone or calcium plus once-weekly elcatonin (Elcitonin, Asahi Kasei Pharma, Tokyo, Japan) injection. Elcatonin treatment markedly improved diverse aspects of the QOL, whereas calcium alone did not. The current data suggest that osteoporosis, especially in the presence of vertebral fracture, is associated with compromised QOL, and therapeutic intervention for osteoporosis should be evaluated in terms of QOL, as well as in terms of increases in bone mineral density and fracture prevention.
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http://dx.doi.org/10.1007/s00774-004-0556-5DOI Listing
June 2005
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