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Taisuke Jo,1,2 Nobuaki Michihata,1 Hayato Yamana,1 Yusuke Sasabuchi,3 Hiroki Matsui,4 Hirokazu Urushiyama,2 Akihisa Mitani,2 Yasuhiro Yamauchi,2 Kiyohide Fushimi,5 Takahide Nagase,2 Hideo Yasunaga4 1Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Data Science Center, Jichi Medical University, Tochigi, Japan; 4Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan; 5Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan Purpose: Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD. Patients and methods: We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy. Results: Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67–0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference. Conclusion: Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD. Keywords: TU-100, herbal medicine, muscarinic receptor antagonists, propensity score, survival analysis

Hiromasa Inoue,1 Takahide Nagase,2 Satoshi Morita,3 Atsushi Yoshida,4 Tatsunori Jinnai,4 Masakazu Ichinose5 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 3Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 4Medical Department, AstraZeneca K.K., Osaka, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background and objective: There is increasing recognition of asthma–COPD overlap syndrome (ACOS), which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood. The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Methods: This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD. Clinical data, including spirometry results, were retrieved from medical records. For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire. Results: Of the 1,008 patients analyzed, 167 (16.6%) had syndromic features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2%) also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1), respectively, and therefore were identified as having ACOS. Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability), and 328 patients (32.5%, ≥12%/≥400 mL FEV1 clinical variability) had both the features. Patients identified as having ACOS were of significantly younger age, had a shorter duration of COPD, lower number of pack-years, better lung function, milder dyspnea symptoms, and higher peripheral blood eosinophil values compared with patients with COPD alone. The rate of exacerbations in the previous year was not significantly different between the ACOS and COPD groups. Conclusion: Using a stepwise approach, as stated in the GINA/GOLD report, the proportions of patients identified as having ACOS were found to be 9.2% and 4.2% (depending on the FEV1 variability cutoff used) among the 1,008 outpatients medically treated for COPD in a real-life clinical setting. Keywords: obstructive lung diseases, airway hyperresponsiveness, respiratory function tests, differential diagnosis

Yukiyo Sakamoto,1 Yasuhiro Yamauchi,1 Hideo Yasunaga,2 Hideyuki Takeshima,1 Wakae Hasegawa,1 Taisuke Jo,1,3 Yusuke Sasabuchi,3 Hiroki Matsui,2 Kiyohide Fushimi,4 Takahide Nagase1 1Department of Respiratory Medicine, Graduate School of Medicine, 2Department of Clinical Epidemiology and Health Economics, School of Public Health, 3Department of Health Services Research, Graduate School of Medicine, University of Tokyo, 4Department of Health Policy and Informatics, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan Background and objectives: Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of their disease, sometimes requiring hospital admission and being associated with increased mortality. Although previous studies have reported mortality from exacerbations of COPD, there is limited information about prediction of individual in-hospital mortality. We therefore aimed to use data from a nationwide inpatient database in Japan to generate a nomogram for predicting in-hospital mortality from patients’ characteristics on admission.Methods: We retrospectively collected data on patients with COPD who had been admitted for exacerbations and been discharged between July 1, 2010 and March 31, 2013. We performed multivariable logistic regression analysis to examine factors associated with in-hospital mortality and thereafter used these factors to develop a nomogram for predicting in-hospital prognosis.Results: The study comprised 3,064 eligible patients. In-hospital death occurred in 209 patients (6.8%). Higher mortality was associated with older age, being male, lower body mass index, disturbance of consciousness, severe dyspnea, history of mechanical ventilation, pneumonia, and having no asthma on admission. We developed a nomogram based on these variables to predict in-hospital mortality. The concordance index of the nomogram was 0.775. Internal validation was performed by a bootstrap method with 50 resamples, and calibration plots were found to be well fitted to predict in-hospital mortality.Conclusion: We developed a nomogram for predicting in-hospital mortality of exacerbations of COPD. This nomogram could help clinicians to predict risk of in-hospital mortality in individual patients with COPD exacerbation. Keywords: chronic obstructive pulmonary disease, exacerbation, in-hospital mortality, nomogram

We report a rare case of proximal tibiofibular instability treated using TightRope. An 18-year-old male, soccer player, hit his right knee on the ground with the knee in a flexed position during a game. He was diagnosed with a partial PCL injury by his previous doctor and received a conservative treatment. However, he suffered from right knee pain for 3 months after the injury. The Sijbradij test and proximal tibiofibular joint stress X-rays showed a right-side instability, and we diagnosed the patient with proximal tibiofibular joint instability. We performed proximal tibiofibular joint reconstruction using TightRope. The patient could run 2 months postoperatively and returned to the game 6 months postoperatively. Proximal tibiofibular joint instability is rare, and diagnostic criteria and treatment have not been established. Previous reports have suggested that it is associated with radiating pain of the common peroneal nerve and general joint laxity. Joint fixation using metal screws is associated with the risk of screw breakage owing to weight bearing, which necessitates peroneal osteotomy and metal removal. Proximal tibiofibular reconstruction using TightRope is a minimally invasive and effective technique that enables micro-motion, and is similar to physiologic ligament reconstruction. TightRope doesn't require peroneal osteotomy or metal removal. [ABSTRACT FROM AUTHOR]

Yasuhiro Yamauchi,1 Hideo Yasunaga,2 Yukiyo Sakamoto,1 Wakae Hasegawa,1 Hideyuki Takeshima,1 Hirokazu Urushiyama,1 Taisuke Jo,1,3 Hiroki Matsui,2 Kiyohide Fushimi,4 Takahide Nagase1 1Department of Respiratory Medicine, Graduate School of Medicine, 2Department of Clinical Epidemiology and Health Economics, School of Public Health, 3Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, 4Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan Background and objective: COPD is well known to frequently coexist with osteoporosis. Bone fractures often occur and may affect mortality in COPD patients. However, in-hospital mortality related to bone fractures in COPD patients has been poorly studied. This retrospective study investigated in-hospital mortality of COPD patients with bone fractures using a national inpatient database in Japan.Methods: Data of COPD patients admitted with bone fractures, including hip, vertebra, shoulder, and forearm fractures to 1,165 hospitals in Japan between July 2010 and March 2013, were extracted from the Diagnosis Procedure Combination database. The clinical characteristics and mortalities of the patients were determined. Multivariable logistic regression analysis was also performed to determine the factors associated with in-hospital mortality of COPD patients with hip fractures.Results: Among 5,975 eligible patients, those with hip fractures (n=4,059) were older, had lower body mass index (BMI), and had poorer general condition than those with vertebral (n=1,477), shoulder (n=281), or forearm (n=158) fractures. In-hospital mortality was 7.4%, 5.2%, 3.9%, and 1.3%, respectively. Among the hip fracture group, surgical treatment was significantly associated with lower mortality (adjusted odds ratio, 0.43; 95% confidence interval, 0.32–0.56) after adjustment for patient backgrounds. Higher in-hospital mortality was associated with male sex, lower BMI, lower level of consciousness, and having several comorbidities, including pneumonia, lung cancer, congestive heart failure, chronic liver disease, and chronic renal failure.Conclusion: COPD patients with hip fractures had higher mortality than COPD patients with other types of fracture. Surgery for hip fracture was associated with lower mortality than conservative treatment. Keywords: COPD, hip fractures, in-hospital mortality, surgical treatment

Yasuhiro Yamauchi,1 Hideo Yasunaga,2 Wakae Hasegawa,1 Yukiyo Sakamoto,1 Hideyuki Takeshima,1 Taisuke Jo,1,3 Hiroki Matsui,2 Kiyohide Fushimi,4 Takahide Nagase1 1Department of Respiratory Medicine, Graduate School of Medicine, 2Department of Clinical Epidemiology and Health Economics, School of Public Health, 3Division for Health Service Promotion, The University of Tokyo, 4Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan Background and objectives: Inhaled corticosteroids (ICS) and long-acting inhaled bronchodilators (IBD) are beneficial for the management of COPD. Although ICS has been reported to increase the risk of pneumonia in patients with COPD, it remains controversial whether it influences mortality. Using a Japanese national database, we examined the association between preadmission ICS therapy and in-hospital mortality from pneumonia in patients with COPD. Methods: We retrospectively collected data from 1,165 hospitals in Japan on patients with COPD who received outpatient inhalation therapy and were admitted with pneumonia. Patients were categorized into those who received ICS with IBD and those who received IBD alone. We performed multivariate logistic regression analysis to examine the association between outpatient ICS therapy and in-hospital mortality, adjusting for the patients’ backgrounds. Results: Of the 7,033 eligible patients, the IBD alone group (n=3,331) was more likely to be older, have lower body mass index, poorer general conditions, and more severe pneumonia than the ICS with IBD group (n=3,702). In-hospital mortality was 13.2% and 8.1% in the IBD alone and the ICS with IBD groups, respectively. After adjustment for patients’ backgrounds, the ICS with IBD group had significantly lower mortality than the IBD alone group (adjusted odds ratio, 0.80; 95% confidence interval, 0.68–0.94). Higher mortality was associated with older age, being male, lower body mass index, poorer general status, and more severe pneumonia. Conclusion: Outpatient inhaled ICS and IBD therapy was significantly associated with lower mortality from pneumonia in patients with COPD than treatment with IBD alone. Keywords: inhaled corticosteroids, bronchodilators, in-hospital mortality, pneumonia, COPD

Toshiko Kaitani,1 Gojiro Nakagami,2 Junko Sugama,3 Masahiro Tachi,4 Yutaka Matsuyama,5 Yoshiki Miyachi,6 Takashi Nagase,2 Yukie Takemura,7 Hiromi Sanada2 1School of Nursing, Sapporo City University, Hokkaido, Japan; 2Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Department of Clinical Nursing, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; 4Department of Plastic Surgery, Tohoku University Graduate School of Medicine, Miyagi, Japan; 5Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 6Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; 7Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Aims and objectives: We investigated the effectiveness and safety of an advanced pressure ulcer (PU) management protocol comprising 1) ultrasonography to assess the deep tissue, 2) use of a non-contact thermometer to detect critical colonization, 3) conservative sharp debridement, 4) dressing selection, 5) negative pressure wound therapy, and 6) vibration therapy in comparison with those of a conventional approach. Each protocol was followed by trained wound, ostomy, and continence nurses (WOCNs). Background: At present, there is no systematic PU management protocol for nurses that includes appropriate assessment and intervention techniques for deep tissue injury and critical colonization. In Japan, there is no such protocol that the nurses can follow without a physician’s orders. Design and methods: This was a prospective non-randomized controlled trial. Over a 3-week period, we evaluated the effectiveness of an advanced protocol by comparing the PU severity and healing on the basis of the DESIGN-R scale and presence of patients' discomfort. We recruited ten WOCNs to follow the advanced protocol and 19 others as controls. Statistical analysis included a linear mixed-effects model and a logistic regression model. Results: In week 0–1, the advanced protocol was significantly associated with prevention of PU deterioration. Using the linear mixed-effects model, we observed a greater decrease in the DESIGN-R score (healing) in the advanced protocol group. There were no reports of excessive bleeding, pain or infection with the advanced protocol. Conclusion: Using the advanced protocol, WOCNs detected PU severity, assessed PUs, and treated PUs safely. This protocol prevented PU deterioration and/or facilitated wound healing. Relevance to clinical practice: With proper training, WOCNs can assess and treat PUs safer and quicker than when a physician's assessment is required, leading to an improvement in wound healing and prevention of PU deterioration. Keywords: pressure ulcers, WOCN, interventions, protocols, deep tissue injury

Yasuhiro Yamauchi,1,2 Wakae Hasegawa,1 Hideo Yasunaga,3 Mitsuhiro Sunohara,1 Taisuke Jo,1,2 Kazutaka Takami,1 Hiroki Matsui,3 Kiyohide Fushimi,4 Takahide Nagase1 1Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 2Division for Health Service Promotion, The University of Tokyo, Tokyo, Japan; 3Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan; 4Department of Health Policy and Informatics, Tokyo Medical and Dental University, Graduate School of Medicine, Tokyo, Japan Background and objective: The prevalence and mortality of chronic obstructive pulmonary disease (COPD) in elderly patients are increasing worldwide. Low body mass index (BMI) is a well-known prognostic factor for COPD. However, the obesity paradox in elderly patients with COPD has not been well elucidated. We investigated the association between BMI and in-hospital mortality in elderly COPD patients. Methods: Using the Diagnosis Procedure Combination database in Japan, we retrospectively collected data for elderly patients (>65 years) with COPD who were hospitalized between July 2010 and March 2013. We performed multivariable logistic regression analysis to compare all-cause in-hospital mortality between patients with BMI of

Yasuhiro Yamauchi1,2, Tadashi Kohyama2, Taisuke Jo2, Takahide Nagase21Division of Health Promotion Center, 2Department of Respiratory Medicine, University of Tokyo, Tokyo, JapanBackground and objective: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation consisting of airway obstruction and parenchymal emphysema, with loss of elastic recoil. The forced oscillation technique can detect impairment of lung function by measuring lung impedance during normal tidal breathing. Respiratory resistance (Rrs) in COPD has been well-studied, but the differences in Rrs in the inspiratory and expiratory phases between mild and moderate COPD remain poorly understood. Since airway obstruction in COPD is known to change dynamically during tidal breathing and might affect Rrs, the differences in Rrs during tidal breathing between mild and moderate COPD were evaluated.Methods: Mild (n = 13) and moderate (n = 13) COPD patients were recruited at Tokyo University Hospital (Tokyo, Japan). Rrs was measured using MostGraph-01 (Chest MI, Inc, Tokyo, Japan), which depicted Rrs in a frequency- and respiratory cycle-dependent manner in three-dimensional graphics. Rrs was evaluated at 4–35 Hz during tidal breathing.Results: Rrs changed dynamically during tidal breathing in COPD. The mean Rrs values were significantly greater in the moderate COPD group than in the mild group. The maximal and minimal Rrs values at higher frequencies in the respiratory cycle were significantly greater in moderate COPD. In inspiratory–expiratory breath analysis, the maximal and minimal Rrs values at 20 Hz and 35 Hz were significantly greater in the moderate group, whereas at 4 Hz they did not differ significantly between the groups.Conclusion: Rrs changed dynamically during tidal breathing in patients with COPD. The Rrs values at higher frequencies were greater in moderate COPD than in mild COPD. Rrs at higher frequencies might reflect the degree of airway obstruction in tidal breathing in patients with COPD and might be a useful marker for evaluation of airway obstruction at an early stage of COPD.Keywords: COPD, airflow limitation, respiratory resistance, forced oscillation technique

Thermodynamic studies are used for analyzing the mechanism of structural transition in nanocrystalline metals. The results have shown that relative to the crystallized nanocrystalline state, the face centered cubic (fcc) Fe has formed in the milled nanocrystalline state.

The microscopic structure of FePtCu ternary ordered alloys from both theoretical and experimental points of view is investigated. The findings from a comparison with the calculated density of states curve show that the Fe site of FePt ordered alloy replaced the Cu.