Determination of the reference value and systematic bias of the functional reach test in Japanese elderly people by meta-analysis

AbstractBackground/PurposeThe functional reach test (FRT), which was developed as a clinical balance assessment tool, has been widely used as a fall risk assessment tool in elderly people. The aim of the present study was to investigate the reference value and the presence of systematic bias in the FRT using the methodology of meta-analysis in community-dwelling elderly people.MethodsRelevant research articles were sought from electronic databases: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Igakucyuouzasshi. The search was conducted from January 1990 to August 2011, and the terms “functional reach” and “elderly” were used in combination in the search. The searches were limited to peer-reviewed research articles involving Japanese elderly people with good functioning, aged 60 years and older. Weighted means were calculated for the reference value of FRT by a fixed effect model and a random effect model. Furthermore, weighted least squares regression was performed to determine the presence of systematic bias in the reference value of FRT.ResultsA total of 19 articles fulfilled the inclusion criteria, including 4274 participants whose mean age ranged from 69.0 to 81.4 years. The reference value of FRT was 29.44 cm (95% confidence interval: 27.60–31.27 cm) using the random-effect model, since the reference value using the fixed-effect model was found to have significant heterogeneity. Furthermore, multivariate weighted least squares regression was performed, and sex, age, height, and measurement method (one-arm or two-arm reach) were all independently associated with the FRT value (multiple R2 = 0.295, χ2 = 76.6, p < 0.001).ConclusionsSince participants' characteristics (sex, age, and height) and measurement method are probably related to systematic error in the FRT, judgment of physical function in elderly people using only the reference value determined in this study may have limitations

Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a nationwide analysis of the Japan renal biopsy registry from 2007 to 2015

BackgroundThe incidence and age distribution of membranoproliferative glomerulonephritis (MPGN) vary throughout the world by race and ethnicity. We sought to evaluate the clinical features, pathogenesis, and age distribution of MPGN among a large nationwide data from the Japan Renal Biopsy Registry (J-RBR).MethodsA cross-sectional survey of 593 patients with MPGN (types I and III) registered in the J-RBR between 2007 and 2015 was conducted. Clinical parameters, and laboratory findings at diagnosis were compared between children (< 20 years), adults (20–64 years), and elderly patients (≥ 65 years).ResultsThe median age of the patients was 59.0 years and mean proteinuria was 3.7 g/day. The rate of nephrotic syndrome was significantly higher in adults (40.4%) and elderly patients (54.0%) than in children (14.9%), whereas the rate of chronic glomerulonephritis was significantly higher in children (66.2%) than in adults (34.4%) and elderly patients (31.2%). According to the CGA risk classification, high-risk (red zone) cases accounted for 3.4% of children, 52.5% of adults and 84.1% of elderly patients with MPGN. As for pathogenesis, primary MPGN was most frequent (56.0%). Lupus nephritis was the most common disease among adult patients with secondary MPGN, whereas infectious disease was more common in elderly patients. Multiple regression analysis revealed that high systolic blood pressure and high proteinuria were independent factors associated with decreased estimated glomerular filtration rate (eGFR) in adults and elderly patients with MPGN.ConclusionsIn Japan, adults and elderly patients with MPGN had a lower eGFR and severer proteinuria than children

Assessing Versatile Machine Learning Models for Glioma Radiogenomic Studies across Hospitals

Radiogenomics use non-invasively obtained imaging data, such as magnetic resonance imaging (MRI), to predict critical biomarkers of patients. Developing an accurate machine learning (ML) technique for MRI requires data from hundreds of patients, which cannot be gathered from any single local hospital. Hence, a model universally applicable to multiple cohorts/hospitals is required. We applied various ML and image pre-processing procedures on a glioma dataset from The Cancer Image Archive (TCIA, n = 159). The models that showed a high level of accuracy in predicting glioblastoma or WHO Grade II and III glioma using the TCIA dataset, were then tested for the data from the National Cancer Center Hospital, Japan (NCC, n = 166) whether they could maintain similar levels of high accuracy. Results: we confirmed that our ML procedure achieved a level of accuracy (AUROC = 0.904) comparable to that shown previously by the deep-learning methods using TCIA. However, when we directly applied the model to the NCC dataset, its AUROC dropped to 0.383. Introduction of standardization and dimension reduction procedures before classification without re-training improved the prediction accuracy obtained using NCC (0.804) without a loss in prediction accuracy for the TCIA dataset. Furthermore, we confirmed the same tendency in a model for IDH1/2 mutation prediction with standardization and application of dimension reduction that was also applicable to multiple hospitals. Our results demonstrated that overfitting may occur when an ML method providing the highest accuracy in a small training dataset is used for different heterogeneous data sets, and suggested a promising process for developing an ML method applicable to multiple cohort

Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non‐taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M‐phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation‐induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient‐derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BACKGROUND: The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. METHODS: This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71-75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. DISCUSSION: If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. TRIAL REGISTRATION: Registry number: jRCTs031200099 . Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020

J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m² base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39, 121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m²) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1, 001 (2.6%), 2, 612 (6.7%), 23, 333 (59.6%), 8, 357 (21.4%), 2, 710 (6.9%) and 1, 108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB)

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD. Methods: In total, 31, 082 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively. Results: The mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09–2.58]), G4 (5.50 [4.80–6.31]), and G5 (9.75 [8.13–11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5. Conclusions: We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study

Isospin character of low-lying states in 56Fe.

Low-lying states in {sup 56}Fe, up to an excitation energy of about 4 MeV, have been investigated by means of inelastic proton and deuteron scattering experiments at {ital E}{sub {ital p}}=65 and 400 MeV and at {ital E}{sub {ital d}}=56 MeV, respectively. Measured cross sections and analyzing powers have been compared with coupled-channels calculations using collective form factors; calculations in both the Schr{umlt o}dinger and Dirac formalisms have been carried out for the proton data. For each probe, the matrix elements have been deduced for transitions from the ground state and from the 2{sub 1}{sup +} state to six quadrupole (2{sup +}) states to one octupole (3{sub 1}{sup {minus}}) and two hexadecapole (4{sub 1}{sup +} and 4{sub 2}{sup +}) states. The obtained matrix elements and the previous values from {gamma} decay or electron inelastic scattering have been used to evaluate the isospin character of the transitions. To discuss the quadrupole mixed-symmetry states in {sup 56}Fe, the deduced neutron ({ital M}{sub {ital n}}) and proton ({ital M}{sub {ital p}}) components of the matrix elements, or equivalently the isoscalar ({ital M}{sub {ital s}}) and isovector ({ital M}{sub {ital v}}) parts, have been compared with theoretical calculations based on the neutron-proton interacting bosonmore » model and on the shell model evaluated in a full {ital f}-{ital p} configuration space. {copyright} {ital 1996 The American Physical Society.}« les