研究者詳細 - 長島　健悟

論文 - 長島　健悟

分割表示 148 件中 101 - 120 件目／全件表示 >>

Heart rate and oxygen saturation change patterns during 6-min walk test in subjects with chronic thromboembolic pulmonary hypertension

Inagaki T, Terada J, Yahaba M, Kawata N, Jujo T, Nagashima K, Sakao S, Tanabe N, Tatsumi K

Respiratory Care 63 （ 5 ） 573 - 583 2018年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00201324

BACKGROUND: The 6-min walk test (6MWT) is commonly performed to assess functional status in patients with chronic thromboembolic pulmonary hypertension. However, changes in heart rate and oxygen saturation (S ) patterns during 6MWT in patients with chronic thromboembolic pulmonary hypertension remain unclear. METHODS: Thirty-one subjects with chronic thromboembolic pulmonary hypertension were retrospectively evaluated to examine the relationships between the change in heart rate (Δheart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery during the first minute after 6MWT (HRR1), change in S (ΔS ), S reduction time, and S recovery time during 6MWT, and the severity of pulmonary hemodynamics assessed by right heart catheterization and echocardiography. RESULTS: Subjects with severe chronic thromboembolic pulmonary hypertension had significantly longer heart rate acceleration time (144.9 ± 63.9 s vs 96.0 ± 42.5 s, P = .033), lower Δheart rate (47.4 ± 16.9 vs 61.8 ± 13.6 beats, P = .02), and lower HRR1 (13.3 ± 9.0 beats vs 27.1 ± 9.2 beats, P < .001) compared to subjects with mild chronic thromboembolic pulmonary hypertension. Subjects with severe chronic thromboembolic pulmonary hypertension also had significantly longer S reduction time (178.3 ± 70.3 s vs 134.3 ± 58.4 s, P = .03) and S recovery time (107.6 ± 35.3 s vs 69.8 ± 32.7 s, P = .004) than did subjects with mild chronic thromboembolic pulmonary hypertension. Multivariate linear regression analysis showed only mean pulmonary arterial pressure independently was associated with heart rate acceleration time and slope of heart rate acceleration. CONCLUSIONS: Heart rate and S change patterns during 6MWT are predominantly associated with pulmonary hemodynamics in subjects with chronic thromboembolic pulmonary hypertension. Evaluating heart rate and S change patterns during 6MWT may serve as a safe and convenient way to follow the change in pulmonary hemodynamics. pO2 pO2 pO2 pO2 pO2 pO2 pO2 pO2 pO 2

Access to Document (DOI)

Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study)

Koshizaka M, Ishikawa K, Ishikawa T, Kobayashi K, Takemoto M, Horikoshi T, Shimousa R, Takahashi S, Nagashima K, Sato Y, Tatsuno I, Terano T, Hashimoto N, Kuribayashi N, Uchida D, Yokote K, on behalf of the PRIME-V Study Investigators

BMJ Open 7 （ 5 ） e015766 2018年05月

研究論文（学術雑誌）, 共著, 査読有り

Introduction In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required. Therefore, we aim to determine the effects of treatment with SGLT-2 inhibitors or metformin for reducing visceral fat in 106 Asian patients with type 2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50 mg daily) for poor glycaemic control. Methods and analysis A prospective, multicentre, blinded-endpoint phase IV randomised controlled study will be conducted to evaluate the safety and efficacy of a 24-week treatment with either an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg daily) or metformin (1000 mg daily). The primary outcome is the rate of change in the total area of visceral fat for patients in both treatment groups, measured using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical information, will perform centralised analysis of the images in a unified measurement condition. Ethics and dissemination The protocol was approved by the institutional review board of each hospital. This study is ongoing and due to finish in April 2017. The findings of this study will be disseminated via peer-reviewed publications and conference presentations, and will also be disseminated to participants.

Access to Document (DOI)

A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy

Yanai T, Iwasa S, Hashimoto H, Ohyanagi F, Takiguchi T, Takeda K, Nakao M, Sakai H, Nakayama T, Minato K, Arai T, Suzuki K, Shimada Y, Nagashima K, Terakado H, Yamamoto N

International Journal of Clinical Oncology 23 （ 2 ） 382 - 388 2018年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13419625

Purpose: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). Methods: A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m ). Patients were randomly assigned either olanzapine 10 or 5 mg orally on days 1–4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24–120 h after the start of cisplatin treatment). Results: 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3–83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2–90.7, P < 0.001) in the 5 mg group (P value for H : complete response rate ≤ 65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups, respectively. Conclusions: Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. Clinical Trial Information: UMIN000014214. 2 0

Access to Document (DOI)

Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea

Matsumura T, Terada J, Kinoshita T, Sakurai Y, Yahaba M, Tsushima K, Sakao S, Nagashima K, Ozaki T, Kobayashi Y, Hiwasa T, Tatsumi K

PLoS ONE 13 （ 3 ） e0195015 2018年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1932-6203

Objective Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. Methods Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. Results NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. Conclusions Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further. 2

Access to Document (DOI)

Impact of arterial stiffness on WatchPAT variables in patients with obstructive sleep apnea

Kinoshita T, Yahaba M, Terada J, Matsumura T, Sakurai Y, Sakao S, Nagashima K, Tatsumi K

Journal of Clinical Sleep Medicine 14 （ 3 ） 319 - 325 2018年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 15509389

Study Objectives: The WatchPAT is a wrist-worn portable device that creates integration data regarding peripheral arterial tone (PAT), oxyhemoglobin saturation, heart rate, and actigraphy to diagnose or screen for obstructive sleep apnea (OSA). Previous studies have demonstrated the efficacy and validity of respiratory variables measured by the WatchPAT compared to those using polysomnography (PSG). However, the effects of arterial stiffness or atherosclerosis on WatchPAT parameters remain to be elucidated. Methods: Sixty-one consecutive patients with suspected OSA who underwent home-based testing with the WatchPAT 200, standard in-laboratory overnight polysomnography (PSG), and pulse wave velocity (PWV) as an index of arterial stiffness were studied. All PSG recordings were scored manually using the American Academy of Sleep Medicine criteria, whereas WatchPAT data were analyzed by an automatic algorithm. We evaluated how arterial stiffness affected respiratory event index data in WatchPAT (WP-AHI), because WP-AHI could be partly influenced by PAT, comparing WP-AHI and the apneahypopnea index measured by PSG (PSG-AHI) in consideration of PWV result. Results: Overall, WP-AHI was moderately correlated to PSG-AHI, but WP-AHI was significantly lower than PSG-AHI (28.4 ± 19.2 versus 53.6±30.2 events/h, P<.0001). For the lower PWV group, there was a significant correlation and good agreement between the WP-AHI and PSG-AHI, but as the PWV increased, there was low correlation between the WP-AHI and PSG-AHI. Conclusions: Arterial stiffness may affect the respiratory variables measured by WatchPAT in patients with OSA.

Access to Document (DOI)

Trends in study design and the statistical methods employed in a leading general medicine journal

Gosho M, Sato Y, Nagashima K, Takahashi S

Journal of Clinical Pharmacy and Therapeutics 43 （ 1 ） 36 - 44 2018年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 02694727

What is known and objective: Study design and statistical methods have become core components of medical research, and the methodology has become more multifaceted and complicated over time. The study of the comprehensive details and current trends of study design and statistical methods is required to support the future implementation of well-planned clinical studies providing information about evidence-based medicine. Our purpose was to illustrate study design and statistical methods employed in recent medical literature. Methods: This was an extension study of Sato et al. (N Engl J Med 2017; 376: 1086-1087), which reviewed 238 articles published in 2015 in the New England Journal of Medicine (NEJM) and briefly summarized the statistical methods employed in NEJM. Using the same database, we performed a new investigation of the detailed trends in study design and individual statistical methods that were not reported in the Sato study. Results and discussion: Due to the CONSORT statement, prespecification and justification of sample size are obligatory in planning intervention studies. Although standard survival methods (eg Kaplan-Meier estimator and Cox regression model) were most frequently applied, the Gray test and Fine-Gray proportional hazard model for considering competing risks were sometimes used for a more valid statistical inference. With respect to handling missing data, model-based methods, which are valid for missing-at-random data, were more frequently used than single imputation methods. These methods are not recommended as a primary analysis, but they have been applied in many clinical trials. Group sequential design with interim analyses was one of the standard designs, and novel design, such as adaptive dose selection and sample size re-estimation, was sometimes employed in NEJM. What is new and conclusion: Model-based approaches for handling missing data should replace single imputation methods for primary analysis in the light of the information found in some publications. Use of adaptive design with interim analyses is increasing after the presentation of the FDA guidance for adaptive design.

Access to Document (DOI)

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure …

N Kotooka, M Kitakaze, K Nagashima, M Asaka, Y Kinugasa, K Nochioka, ...

Heart and vessels 33, 866-876 2018年

共著

Actinin-4 protein overexpression as a predictive biomarker in adjuvant chemotherapy for resected lung adenocarcinoma

Shiraishi H, Fujiwara Y, Kakuya T, Tsuta K, Motoi N, Miura N, Watabe Y, Watanabe S-i, Noro R, Nagashima K, Huang W, Yamada T, Asamura H, Ohe Y, Honda K

Biomarkers in Medicine 11 （ 9 ） 721 - 731 2017年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 17520363

Aim: Although several clinical trials demonstrated the benefits of platinum-combination adjuvant chemotherapy for stage II-IIIA lung adenocarcinoma, predictive biomarkers for the efficacy of such therapy have not yet been identified. We evaluated protein overexpression of actinin-4 as a predictive biomarker of the efficacy of adjuvant chemotherapy in resected lung adenocarcinoma. Materials & methods: We measured actinin-4 protein levels in patients with completely resected stage II-IIIA lung adenocarcinoma using immunohistochemistry and then retrospectively compared survival between adjuvant chemotherapy and observation groups. Results: A total of 148 eligible patients were classified into actinin-4 positive or negative cases by immunohistochemistry. In the former, patients with adjuvant chemotherapy survived significantly longer than those with observation (hazard ratio [HR]: 0.307; p = 0.028). But, no significant survival benefit was noted with adjuvant chemotherapy (HR: 0.926; p = 0.876) in the latter. Conclusion: This marker could predict the efficacy of adjuvant chemotherapy for resected lung adenocarcinoma patients.

Access to Document (DOI)

Efficacy and safety of taxane monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: a multicenter retrospective study

Iizumi S, Takashima A, Narita Y, Tajika M, Muro K, Kawai S, Yasui H, Matsushima T, Takahari D, Nagashima K, Boku N

Cancer Chemotherapy and Pharmacology 80 （ 3 ） 575 - 582 2017年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 03445704

Purpose: Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS. Methods: We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0–2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function. Results: A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27–75/42–75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death. Conclusions: Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.

Access to Document (DOI)

Clinical outcomes of resectable esophageal cancer with supraclavicular lymph node metastases treated with curative intent

Honma Y, Hokamura N, Nagashima K, Sudo K, Shoji H, Iwasa S, Takashima A, Kato K, Hamaguchi T, Boku N, Ito Y, Itami J, Koyanagi K, Igaki H, Tachimori Y

Anticancer Research 37 （ 7 ） 3741 - 3749 2017年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 02507005

Background: In the seventh edition of the Union for International Cancer Control (UICC) TNM classification, supraclavicular lymph node (SCLN) in regard to thoracic esophageal cancer (EC) is regarded as a distant organ, therefore, if resectable, SCLN metastasis is considered a candidate for systemic chemotherapy. The purpose of this study was to clarify the survival outcome in patients with resectable thoracic EC with SCLN metastases (M1LYM) treated with curative intent. Patients and Methods: Clinical outcomes in patients with resectable thoracic EC with SCLN metastases (M1LYM) treated by esophagectomy or definitive chemoradiotherapy (dCRT) were retrospectively analyzed. Results: A total of 102 patients were divided in three groups: Surgery with perioperative therapy, n=45; surgery alone, n=19; and dCRT, n=38. Overall, median progression-free survival and median survival time were 9.3 and 26.7 months, respectively. The median survival time was 27.5 months in the group treated with surgery with perioperative treatment, 50.6 months in those treated with surgery alone, and 22 months in the dCRT group. No significant survival difference was seen among the three groupS. Conclusion: Over 30% of patients with resectable M1LYM treated with curative intent achieved long-term survival.

Access to Document (DOI)

Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines, platinum, and taxanes

Nishimura T, Iwasa S, Nagashima K, Okita N, Takashima A, Honma Y, Kato K, Hamaguchi T, Yamada Y, Shimada Y, Boku N

Gastric Cancer 20 （ 4 ） 655 - 662 2017年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 14363291

Background: Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan. Methods: A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes. Results: Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8–2.8] and median overall survival was 4.0 months (95% CI, 2.6–5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan. Conclusion: Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer.

Access to Document (DOI)

Impact of geographic accessibility on utilization of the annual health check-ups by income level in Japan: A multilevel analysis

Fujita M, Sato Y, Nagashima K, Takahashi S, Hata A

PLoS ONE 12 （ 5 ） e0177091 2017年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1932-6203

Although both geographic accessibility and socioeconomic status have been indicated as being important factors for the utilization of health care services, their combined effect has not been evaluated. The aim of this study was to reveal whether an income-dependent difference in the impact of geographic accessibility on the utilization of government-led annual health check-ups exists. Existing data collected and provided by Chiba City Hall were employed and analyzed as a retrospective cohort study. The subjects were 166,966 beneficiaries of National Health Insurance in Chiba City, Japan, aged 40 to 74 years. Of all subjects, 54,748 (32.8%) had an annual health check-up in fiscal year 2012. As an optimal index of geographic accessibility has not been established, five measures were calculated: travel time to the nearest health care facility, density of health care facilities (number facilities within a 30-min walking distance from the district of residence), and three indices based on the two-step floating catchment area method. Three-level logistic regression modeling with random intercepts for household and district of residence was performed. Of the five measures, density of health care facilities was the most compatible according to Akaike's information criterion. Both low density and low income were associated with decreased utilization of the health check-ups. Furthermore, a linear relationship was observed between the density of facilities and utilization of the health check-ups in all income groups and its slope was significantly steeper among subjects with an equivalent income of 0.00 yen than among those with equivalent income of 1.01-2.00 million yen (p = 0.028) or 2.01 million yen or more (p = 0.040). This result indicated that subjects with lower incomes were more susceptible to the effects of geographic accessibility than were those with higher incomes. Thus, better geographic accessibility could increase the health check-up utilization and also decrease the income-related disparity of utilization.

Access to Document (DOI)

The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy

Shoji H, Heike Y, Tada K, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Takashima A, Kato K, Boku N, Honda K, Yamada T, Hamaguchi T

Oncotarget 8 （ 56 ） 95083 - 95094 2017年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1949-2553

Background: The prognostic significance of peripheral immune status in patients with advanced gastric cancer (AGC) remains unclear. Results: From July 2013 through December 2014, 37 patients were enrolled. Among patients with 25 subsets of immune cells, patients in the high group of granulocytic myeloid-derived suppressor cells (Gr-MDSCs) showed significantly shorter progression-free survival (PFS) than those in the low group (3.98 vs. 8.78 months; hazards ratio (HR), 2.61; p = 0.01). In multivariate analysis, the high Gr-MDSCs value was also associated with shorter PFS (HR, 4.60; 95% confidence interval (CI), 1.79-11.8; p = 0.001). Although significant difference was not found in univariate analysis, the high Gr-MDSCs group was associated with shorter overall survival (OS) (HR, 2.89; 95% CI, 1.23-6.80; p = 0.015) in multivariate analysis. Materials and Methods: In this explorative prospective study, peripheral blood samples were collected from AGC patients before initiating first-line cisplatin-based chemotherapy (S-1 + cisplatin or S-1 + cisplatin + docetaxel). Peripheral blood mononuclear cells were analyzed for 25 immune subsets by multicolor flow cytometry. PFS and OS were compared between the patients divided into high and low (≥ and < median, respectively) groups based on the median value for each immune cell subset. Conclusions: The peripheral immune status of Gr-MDSCs appears to affect the prognosis in AGC. Further research is needed to confirm the clinical value of the level of circulating Gr-MDSCs as a prognostic and/or predictive marker in AGC.

Access to Document (DOI)

Quantitative US elastography can be used to quantify mechanical and histologic tendon healing in a rabbit model of Achilles tendon transection

Yamamoto Y, Yamaguchi S, Sasho T, Fukawa T, Akatsu Y, Akagi R, Yamaguchi T, Takahashi K, Nagashima K, Takahashi K

Radiology 283 （ 2 ） 408 - 417 2017年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00338419

Purpose: To determine the time-dependent change in strain ratios (SRs) at the healing site of an Achilles tendon rupture in a rabbit model of tendon transection and to assess the correlation between SRs and the mechanical and histologic properties of the healing tissue. Materials and Methods: Experimental methods were approved by the institutional animal care and use committee. The Achilles tendons of 24 New Zealand white rabbits (48 limbs) were surgically transected. The SRs of Achilles tendons were calculated by using compression-based quantitative ultrasonographic elastography measurements obtained 2, 4, 8, and 12 weeks after transection. After in vivo elastography, the left Achilles tendon was harvested for mechanical testing of ultimate load, ultimate stress, elastic modulus, and linear stiffness, and the right tendons were harvested for tissue histologic analysis with the Bonar scale. Timedependent changes in SRs, mechanical parameters, and Bonar scale scores were evaluated by using repeated-measures analysis of variance. The correlation between SRs and each measured variable was evaluated by using the Spearman rank correlation coefficient. Results: Mean SRs and Bonar scale values decreased as a function of time after transection, whereas mechanical parameters increased (P<.001). SR correlated with ultimate stress (r = 0.68, P ,.001,) elastic modulus (r = 0.74, P ,.001), and the Bonar scale (r = 0.87, P ,.001). Conclusion: Quantitative elastography could be a useful method with which to evaluate mechanical and histologic properties of the healing tendon.

Access to Document (DOI)

Investigation of optimal weight gain during pregnancy for Japanese Women

Nomura K, Kido M, Tanabe A, Nagashima K, Takenoshita S, Ando K

Scientific Reports 7 （ 1 ） 2569 2017年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2045-2322

This study aims to compare the US Institute of Medicine (IOM) and Japanese guidelines proposed by the Ministry and the Japan Society for the Study of Obesity on gestational weight gain (GWG), and to explore the optimal GWG range in Japanese women. We investigated 8,152 Japanese women who had full-term singleton babies between 2010 and 2013 at a single center in Tokyo. Logistic regression models showed that GWG below the recommendation of the IOM and Japanese guidelines was similarly associated with an increased risk of light-for-date (LFD), whereas GWG above these guidelines was similarly associated with an increased risk of heavy-for-date (HFD) in pre-pregnancy body mass index categories of underweight (<18.5 kg/m , n = 1559), normal-weight (18.5-24.9 kg/m , n = 4998), overweight (25.0-29.9 kg/m , n = 270), and obese (30 ≤ kg/m , n = 60). The receiver-operating characteristic curve demonstrated that the optimal cutoffs for LFD and HFD were 9.7 and 10.4 kg, respectively in normal-weight mothers. The IOM and Japanese guidelines identified the risk of LFD or HFD equally well. The optimal GWG range in normal-weight women observed in this study was more close to Japanese guideline (i.e., 7-12 kg) compared to the IOM guideline (i.e., 11.5-16 kg). 2 2 2 2

Access to Document (DOI)

Nishide A, Fujita M, Sato Y, Nagashima K, Takahashi S, Hata A

International Journal of Environmental Research and Public Health 14 （ 5 ） 524 2017年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 16617827

Background: This study aimed to evaluate whether income-related inequalities in access to dental care services exist in Japan. Methods: The subjects included beneficiaries of the National Health Insurance (NHI) in Chiba City, Japan, who had been enrolled from 1 April 2014 to 31 March 2015. The presence or absence of dental visits and number of days spent on dental care services during the year were calculated using insurance claims submitted. Equivalent household income was calculated using individual income data from 1 January to 31 December 2013, declared for taxation. Results: Of the 216,211 enrolled subjects, 50.3% had dental care during the year. Among those with dental visits, the average number of days (standard deviation) spent on dental care services per year was 7.7 (7.1). Low income was associated with a decreased rate of dental care utilization regardless of age and sex. However, there was a significant inverse linear association between the number of days spent on dental care services and income levels for both sexes. Conclusions: There were income-related inequalities in access to dental care services, regardless of the age group or sex, within the Japanese universal health insurance system.

Access to Document (DOI)

Circulating anti-coatomer protein complex subunit epsilon (COPE) autoantibodies as a potential biomarker for cardiovascular and cerebrovascular events in patients with obstructive sleep apnea

Matsumura T, Terada J, Kinoshita T, Sakurai Y, Yahaba M, Ema R, Amata A, Sakao S, Nagashima K, Tatsumi K, Hiwasa T

Journal of Clinical Sleep Medicine 13 （ 3 ） 393 - 400 2017年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 15509389

Study Objectives: Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in patients with OSA. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic complex that mediates protein transport in the Golgi compartment, as a potential novel biomarker of atherosclerosis. This study aimed to evaluate whether COPE-Ab levels had an association with cardiovascular and cerebrovascular events in patients with OSA. Methods: Eighty-two adult patients with a diagnosis of OSA via polysomnography and 64 healthy donors were studied. Serum COPE-Ab levels were measured using an amplified luminescence proximity homogeneous assay. Then, clinical factors related to atherosclerosis were evaluated with respect to COPE-Ab levels. Results: Significant differences in COPE-Ab levels were observed in terms of OSA severity. COPE-Ab levels were significantly higher in patients with OSA and also CVD and/or stroke, hypertension, and a high body mass index. Univariate and multivariate logistic regression analyses of patients with OSA identified elevated COPE-Ab level as a significant predictor of CVD and/or stroke. Conclusions: An elevated COPE-Ab level may be a potential predictor of the risks of cardiovascular and cerebrovascular events in patients with OSA. Therefore, patients with higher COPE-Ab levels may require more careful and intensive treatment. Commentary: A commentary on this article appears in this issue on page 361.

Access to Document (DOI)

A prospective, multi-center, randomized phase II study to evaluate the efficacy and safety of eculizumab in patients with Guillain-Barré syndrome (GBS): Japanese Eculizumab Trial for GBS (JET-GBS)

Yamaguchi N, Misawa S, Sato Y, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kohara N, Hirata K, Nishiyama K, Yabe I, Kaida K-I, Suzuki N, Nodera H, Tsuji S, Koike H, Kira J-I, Hanaoka H, Kusunoki S, Kuwabara S

JMIR Research Protocols 5 （ 4 ） e210 2016年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1929-0748

BACKGROUND: Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation. OBJECTIVE: This clinical trial aims to evaluate the efficacy and safety of eculizumab, a humanized monoclonal antibody directed against complement component 5, for treatment of GBS. METHODS: The Japanese Eculizumab Trial for GBS (JET-GBS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 33 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3-5) were randomized at a 2:1 ratio to receive either intravenous eculizumab (900 mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow-up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial. RESULTS: Enrollment for the trial began in August 2015. This trial is still ongoing. All participants have been enrolled, and follow-up will be completed in October 2016. CONCLUSIONS: This study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients. CLINICALTRIAL: UMIN Clinical Trials Registry UMIN 000018171; https:/upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function= brows&action=brows&type=summary&language=J&recptno=R000020978 (Archived by WebCite at http://www.webcitation.org/ 6lTiG8ltG). Clinical Trials.gov NCT02493725; https://clinicaltrials.gov/ct2/show/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL).

Access to Document (DOI)

Comparison of drug use between clinical practice and regulatory approval: results in older Japanese patients with rheumatoid arthritis, diabetes, high blood pressure, or depression

Tanemura N, Uyama Y, Nagashima K, Suzuki T, Asahina Y, Kobayashi Y, Iyo M, Yokote K, Hanaoka H

Therapeutic Innovation and Regulatory Science 50 （ 6 ） 743 - 750 2016年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 21684790

Background: In this study, differences in older patients between drug use as reported in clinical practice and in clinical trials for regulatory approval were examined. Methods: Electronic medical record (EMR) data such as patient background (age, sex), concomitant drugs, data on laboratory tests, and prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes, high blood pressure, or depression at Chiba University Hospital were obtained for the period from January 2003 to December 2012. These data were compared with data from relevant clinical trials for regulatory approval in order to examine differences in drug use. Results: There were 5134 eligible patients. The prescribed doses of drugs were lower than the standard approved doses for depression and rheumatoid arthritis but were generally within the approved dose range for type 2 diabetes mellitus and hypertension. When comparing the characteristics of older patients taking tacrolimus, 5.6% to 17.0% of those would not be able to participate in clinical trials because of liver or renal abnormality, and the incidence rates of some adverse drug events (ADEs) differed significantly between clinical practice and clinical trials. Conclusions: Appropriate doses of drugs for older patients may differ from approved doses in certain diseases. Complex situations such as a lot of polypharmacy, comorbidity, and functional impairment in older patients in clinical practice make it difficult to evaluate safety based on data from clinical trials. In the future, utilization of a database created from the EMR of older patients should be considered for assessment of drug safety in older patients in clinical practice.

Access to Document (DOI)

Efficacy of intravenous nicorandil for fractional flow reserve assessment: study protocol for a crossover randomised trial

Nishi T, Kitahara H, Fujimoto Y, Nakayama T, Sugimoto K, Nagashima K, Hanaoka H, Kobayashi Y

BMJ Open 6 （ 11 ） e012737 2016年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2044-6055

Introduction: Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. Methods and analysis: This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. Ethics and dissemination: The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals.

Access to Document (DOI)

　前のページ - 次のページ　

長島 健悟

論文 - 長島 健悟

長島　健悟

論文 - 長島　健悟