研究者詳細 - 座間味　義人

論文 - 座間味　義人

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Fall-related mortality trends in older Japanese adults aged ≥65 years: a nationwide observational study. 査読国際誌

Hideharu Hagiya, Toshihiro Koyama, Yoshito Zamami, Yasuhisa Tatebe, Tomoko Funahashi, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Hiromi Rakugi, Mitsunobu R Kano

BMJ open 9 ( 12 ) e033462 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

DOI： 10.1136/bmjopen-2019-033462

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Effect of serum concentration and concomitant drugs on vancomycin-induced acute kidney injury in haematologic patients: a single-centre retrospective study. 査読国際誌

Naoto Okada, Masayuki Chuma, Momoyo Azuma, Shingen Nakamura, Hirokazu Miki, Hirofumi Hamano, Mitsuhiro Goda, Kenshi Takechi, Yoshito Zamami, Masahiro Abe, Keisuke Ishizawa

European journal of clinical pharmacology 75 ( 12 ) 1695 - 1704 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Appropriate use of vancomycin (VCM) is important in preventing acute kidney injury (AKI). Because of the high frequency of VCM use for febrile neutropenia and concomitant use of other nephrotoxic drugs, haematologic patients have a different nephrotoxic background compared with patients with other diseases. Therefore, it is unclear whether the risk factors of VCM-induced AKI identified in other patient groups are also applicable to haematologic patients. Herein, we performed a single-centre retrospective analysis to identify the factors associated with VCM-induced AKI in haematologic patients. METHODS: We retrospectively analysed 150 haematologic patients to whom VCM was administered between April 2010 and March 2018 at Tokushima University Hospital. VCM-induced AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analyses were performed to identify risk factors for VCM-induced AKI. RESULTS: Seventeen patients had VCM-induced AKI. Multivariate analysis revealed that the risk factors of VCM-induced AKI were an initial VCM trough concentration of > 15 mg/L and concomitant use of tazobactam/piperacillin (TAZ/PIPC) and liposomal amphotericin B (L-AMB). Patients with an initial VCM trough concentration of < 10 mg/L showed significantly lower efficacy in febrile neutropenia. Interestingly, concomitant L-AMB use increased the incidence of VCM-induced AKI in a VCM concentration-dependent manner, whereas concomitant TAZ/PIPC increased the incidence in a VCM concentration-independent manner. CONCLUSIONS: The optimal initial VCM trough concentration was 10-15 mg/L in haematologic patients, considering safety and effectiveness. There were differences in the effect of VCM-induced AKI between nephrotoxic drugs.

DOI： 10.1007/s00228-019-02756-4

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Oral anticoagulants usage in Japanese patients aged 18-74 years with non-valvular atrial fibrillation: a retrospective analysis based on insurance claims data. 査読国際誌

Ayako Ohshima, Toshihiro Koyama, Aiko Ogawa, Yoshito Zamami, Hiroyoshi Y Tanaka, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Michael W Miller, Mitsunobu R Kano

Family practice 36 ( 6 ) 685 - 692 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Oral anticoagulants use has increased rapidly, internationally. Here we look at risks and benefits, based on Japanese data, of therapy with low risk non-valvular atrial fibrillation patients. OBJECTIVES: Using a health insurance claims data set we assessed: (i) oral anticoagulants usage in Japan, and (ii) efficacy and safety of dabigatran compared with warfarin, in Japanese patients with non-valvular atrial fibrillation, aged 18-74 years. METHODS: We identified 4380 non-valvular atrial fibrillation patients treated with anticoagulants between 1 January 2005, and 28 February 2014, and estimated the adjusted hazard ratio for stroke or systemic embolism, and any hemorrhagic event (Cox proportional hazards regression model with stabilized inverse probability treatment weighting). RESULTS: The data included 101 989 anticoagulant prescriptions for 4380 patients, of which direct oral anticoagulants increased to 40.0% of the total by the end of the study. After applying exclusion criteria, 1536 new non-valvular atrial fibrillation patients were identified, including 1071 treated with warfarin and 465 with dabigatran. Mean ages were 56.11 ± 9.70 years for warfarin, and 55.80 ± 9.65 years for dabigatran. The adjusted hazard ratio (95% confidence interval), comparing dabigatran with warfarin, was 0.48 (0.25-0.91) for stroke or systemic embolism, and 0.91 (0.60-1.39) for any hemorrhage including intracranial and gastrointestinal. CONCLUSIONS: Number of patients prescribed direct oral anticoagulants steadily increased, and incidence of all-cause bleeding related to dabigatran was similar to warfarin, in our study population of younger non-valvular atrial fibrillation patients. Dabigatran, compared with warfarin, generally reduced risk of all-cause stroke and systemic embolism.

DOI： 10.1093/fampra/cmz016

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認定薬剤師の科学力を考える基礎研究と医療ビッグデータ解析を融合させたドラッグ・リボジショニングへの試み査読

堀ノ内裕也, 池田康将, 福島圭穣, 今西正樹, 濱野裕章, 石澤有紀, 座間味義人, 武智研志, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃

臨床薬理 50 ( Suppl. ) S176 - S176 2019年11月

Prophylactic administration of granulocyte colony-stimulating factor in epirubicin and cyclophosphamide chemotherapy for Japanese breast cancer patients: a retrospective study. 査読国際誌

Takumi Sakurada, Sanako Bando, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Mitsuhiro Goda, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Masami Morimoto, Akira Tangoku, Keisuke Ishizawa

Cancer chemotherapy and pharmacology 84 ( 5 ) 1107 - 1114 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Epirubicin and cyclophosphamide (EC) therapy, a major chemotherapy for patients with early-stage breast cancer, has a low risk (< 10%) of febrile neutropenia (FN). However, data used in reports on the incidence rate of FN were derived primarily from non-Asian populations. In this study, we investigated the FN incidence rate using EC therapy among Japanese patients with breast cancer and evaluated the significance of prophylactic administration of granulocyte colony-stimulating factor (G-CSF). METHODS: We evaluated medical records of patients with early-stage breast cancer who had been treated with EC therapy as neoadjuvant or adjuvant therapy between November 2014 and July 2018. RESULTS: The incidence rate of FN was 23.9%. In patients who received G-CSF as primary prophylaxis, FN expression was completely suppressed. The incidence rate of severe leucopenia/neutropenia, emergency hospitalization, and the use of antimicrobial agents were low in patients receiving primary prophylaxis with G-CSF compared with those not receiving G-CSF (27.3% vs. 64.8%, 9.1% vs. 27.3%, and 27.3% vs. 71.6%, respectively). Furthermore, in all patients who received primary prophylaxis with G-CSF, a relative dose intensity > 85% using EC therapy was maintained. CONCLUSION: The incidence of FN in EC therapy among Japanese patients was higher than expected, EC therapy appears to be a high-risk chemotherapy for FN, and prophylactic administration of G-CSF is recommended. Maintaining high therapeutic intensity is associated with a positive prognosis for patients with early breast cancer, and prophylactic administration of G-CSF is likely to be beneficial in treatment involving EC therapy.

DOI： 10.1007/s00280-019-03948-6

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臨床薬理共同研究推進体制の構築に関する取り組み査読

武智研志, 座間味義人, 肥田典子, 鈴木啓介

臨床薬理 50 ( Suppl. ) S228 - S228 2019年11月

臨床薬理共同研究推進体制の構築に関する取り組み

武智研志, 座間味義人, 肥田典子, 鈴木啓介

臨床薬理 50 ( Suppl. ) S228 - S228 2019年11月

ドラッグリポジショニング手法を用いたバンコマイシン関連腎障害の予防薬探索とその有用性の検討査読

中馬真幸, 合田光寛, 谷友歩, 座間味義人, 武智研志, 石澤有紀, 濱野裕章, 石田俊介, 新村貴博, 近藤正輝, 坂東貴司, 岡田直人, 福島圭穣, 藤野裕道, 土屋浩一郎, 堀ノ内裕也, 池田康将, 楊河宏章, 石澤啓介

日本腎臓病薬物療法学会誌 8 ( 特別号 ) S138 - S138 2019年10月

【医師・看護師のギモンに"的確"かつ"迅速"に答える!病棟・カンファレンスでそのまま使える想定問答集151】(第9章)感染症 (Q109)イトラコナゾール剤形変更時の注意点イトラコナゾールをカプセルから内用液へと切り替える際の注意点を教えてください

岡田直人, 座間味義人, 石澤啓介

薬事 61 ( 14 ) 2690 - 2691 2019年10月

【医師・看護師のギモンに"的確"かつ"迅速"に答える!病棟・カンファレンスでそのまま使える想定問答集151】(第9章)感染症 (Q108)腸ろう患者へのボリコナゾール投与経腸栄養剤を腸ろうから24時間持続投与している患者に対し、ボリコナゾールの経胃投与は可能ですか?

岡田直人, 座間味義人, 石澤啓介

薬事 61 ( 14 ) 2688 - 2689 2019年10月

【医師・看護師のギモンに"的確"かつ"迅速"に答える!病棟・カンファレンスでそのまま使える想定問答集151】(第9章)感染症 (Q107)感染性心内膜炎に対する予防投与感染性心内膜炎の予防では、どのような患者にどのような抗菌薬が使用されますか?

岡田直人, 座間味義人, 石澤啓介

薬事 61 ( 14 ) 2685 - 2687 2019年10月

医療ビッグデータを活用した救急薬学研究査読

中馬真幸, 座間味義人, 合田光寛, 武智研志, 石澤有紀, 新村貴博, 濱野裕章, 近藤正輝, 楊河宏章, 石澤啓介

日本救急医学会雑誌 30 ( 9 ) 506 - 507 2019年9月

Factors Associated With Immune Checkpoint Inhibitor-Related Myocarditis. 査読国際誌

Yoshito Zamami, Takahiro Niimura, Naoto Okada, Toshihiro Koyama, Keijo Fukushima, Yuki Izawa-Ishizawa, Keisuke Ishizawa

JAMA oncology 5 ( 11 ) 1635 - 1637 2019年8月

Pattern of antibiotic prescriptions for outpatients with acute respiratory tract infections in Japan, 2013-15: A retrospective observational study 査読

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Mayu Adachi, Ayako Ohshima, Yoshito Zamami, Hiroyoshi Y. Tanaka, Yasuhisa Tatebe, Ken Tasaka, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Mitsunobu R. Kano, Shiro Hinotsu, Toshiaki Sendo

Family Practice 36 ( 4 ) 402 - 409 2019年8月

Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress. 査読国際誌

Yasumasa Ikeda, Akiho Satoh, Yuya Horinouchi, Hirofumi Hamano, Hiroaki Watanabe, Mizuki Imao, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Ken-Ichi Aihara, Koichiro Tsuchiya, Toshiaki Tamaki

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 ( 8 ) 9551 - 9564 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via a ubiquitin ligase-dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration in vivo and C2C12 mouse myoblast cells in vitro. In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. In vitro, iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis via oxidative stress, leading to an imbalance in skeletal muscle homeostasis.-Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress.

DOI： 10.1096/fj.201802724RR

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Pattern of antibiotic prescriptions for outpatients with acute respiratory tract infections in Japan, 2013-15: a retrospective observational study. 査読国際誌

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Mayu Adachi, Ayako Ohshima, Yoshito Zamami, Hiroyoshi Y Tanaka, Yasuhisa Tatebe, Ken Tasaka, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Mitsunobu R Kano, Shiro Hinotsu, Toshiaki Sendo

Family practice 36 ( 4 ) 402 - 409 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. PURPOSE: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. METHODS: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. RESULTS: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. CONCLUSIONS: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

DOI： 10.1093/fampra/cmy094

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Nerve growth factor (NGF) has an anti-tumor effects through perivascular innervation of neovessels in HT1080 fibrosarcoma and HepG2 hepatitis tumor in nude mice. 査読

Hiromu Kawasaki, Mitsuhiro Goda, Satoko Fukuhara, Narumi Hashikawa-Hobara, Yoshito Zamami, Shingo Takatori

Journal of pharmacological sciences 140 ( 1 ) 1 - 7 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study investigated whether NGF prevents tumor growth by promoting neuronal regulation of tumor blood flow. HT1080 fibrosarcoma cells or HepG2 hepatitis cells were subcutaneously implanted into nude mice. On Day 21 after the implantation of tumor cells, human NGF (40 or 80 ng/h for 14 days) was administered using a micro-osmotic pump. Growth rates of both tumors were significantly inhibited by the treatment of NGF, and the survival rate was also extended. Significant suppression of HT1080 tumor growth lasted after withdrawing NGF. NGF markedly increased the density of α-smooth muscle actin (α-SMA)-immunoreactive (ir) cells without changing neovessel density in HT1080 tumor tissues. Double immunostaining demonstrated protein gene product (PGP) 9.5-ir nerves around α-SMA-ir cells were found in HT1080 tumor tissue treated with NGF. The blood flow in HepG2 tumors treated with saline was significantly higher than in the non-tumor control area, but the tumor blood flow was markedly reduced by NGF treatment. In in vitro studies, NGF significantly accelerated migration of aortic smooth muscle cells but not endothelial cells, whereas NGF had no cytotoxic action on both cells. NGF inhibits tumor growth via indirect action, probably through innervation and maturation of tumor neovasculature, which regulates blood flow into tumor tissues.

DOI： 10.1016/j.jphs.2019.02.011

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Association between rapid antigen detection tests and antibiotics for acute pharyngitis in Japan: A retrospective observational study. 査読国際誌

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Ayako Ohshima, Yoshito Zamami, Yasuhisa Tatebe, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 4 ) 267 - 272 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The application and clinical impact of rapid antigen detection test (RADT) in the treatment of acute pharyngitis is unknown in Japan. We aimed to examine the proportions of RADT usage to identify Group A β-hemolytic Streptococcus (GAS) in outpatients with acute pharyngitis and evaluate the association between RADT and antibiotic treatment. We analyzed health insurance claims data from 2013 to 2015. Logistic regression models were used to analyze associated factors with RADT, overall antibiotic prescription, or penicillin use. We analyzed 1.27 million outpatient visits with acute pharyngitis, in which antibiotics were prescribed in 59.3% of visits. Of the total visits, 5.6% of patients received RADT, and 10.8% of the antibiotics were penicillin. Penicillin selection rates were higher in cases with RADT (25.4%) than those without RADT (9.7%). Compared to large-scale facilities, antibiotic prescription rates were higher in physicians' offices. For factor analysis, age (3-15 years), diagnosis code (streptococcal pharyngitis), size of the medical facility (large-scale hospitals), and physician's specialty (pediatrics) were associated with RADT use. Penicillin selection rate increased with RADT implementation (25.4% vs. 9.7%: adjusted odds ratio 1.55; 95% CI, 1.50-1.60). At 63% of the facilities, the RADT implementation rate was <5% of acute pharyngitis visits prescribed antibiotics. In conclusion, the proportion of RADT usage for outpatients with acute pharyngitis was low in Japan. With appropriate indication and evaluation, we expect that more utilization of RADT can help promote antimicrobial stewardship for outpatients with acute pharyngitis by prompting penicillin therapy. Further investigation with detailed clinical data are warranted.

DOI： 10.1016/j.jiac.2018.12.005

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Factors Affecting the Absorption of Midazolam to the Extracorporeal Membrane Oxygenation Circuit. 査読

Atsuyoshi Iida, Hiromichi Naito, Takashi Yorifuji, Yoshito Zamami, Akane Yamada, Tadashi Koga, Toru Imai, Toshiaki Sendo, Atsunori Nakao, Shingo Ichiba

Acta medica Okayama 73 ( 2 ) 101 - 107 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sedatives are administered during extracorporeal membrane oxygenation (ECMO) therapy to ensure patient safety, reduce the metabolic rate and correct the oxygen supply-demand balance. However, the concentrations of sedatives can be decreased due to absorption into the circuit. This study examined factors affecting the absorption of a commonly used sedative, midazolam (MDZ). Using multiple ex vivo simulation models, three factors that may influence MDZ levels in the ECMO circuit were examined: polyvinyl chloride (PVC) tubing in the circuit, use of a membrane oxygenator in the circuit, and heparin coating of the circuit. We also assessed changes in drug concentration when MDZ was re-injected in a circuit. The MDZ level decreased to approximately 60% of the initial concentration in simulated circuits within the first 30 minutes. The strongest factor in this phenomenon was contact with the PVC tubing. Membrane oxygenator use tended to increase MDZ loss, whereas heparin circuit coating had no influence on MDZ absorption. Similar results were obtained when a second dose of MDZ was injected to the second-use circuits.

DOI： 10.18926/AMO/56645

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Irinotecan-induced neutropenia is reduced by oral alkalization drugs: analysis using retrospective chart reviews and the spontaneous reporting database. 査読国際誌

Hirofumi Hamano, Marin Mitsui, Yoshito Zamami, Kenshi Takechi, Takahiro Nimura, Naoto Okada, Keijo Fukushima, Masaki Imanishi, Masayuki Chuma, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Yasumasa Ikeda, Hiromichi Fujino, Hiroaki Yanagawa, Toshiaki Tamaki, Keisuke Ishizawa

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 27 ( 3 ) 849 - 856 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied. The aim of this study was to investigate the relationship between oral alkalization drugs and neutropenia in irinotecan-treated patients. METHODS AND RESULTS: Patients with cervical or ovarian cancer were administered irinotecan and investigated by medical chart reviews to determine whether oral alkalization drugs were effective at ameliorating irinotecan-induced neutropenia. The drug combination in the oral alkalization drugs-ursodeoxycholic acid, magnesium oxide, and sodium hydrogen carbonate-significantly improved neutrophil counts and reduced dose intensity compared with those of non-users. In the large-scale Japanese Adverse Drug Event Report database, the reporting odds ratio of irinotecan-induced neutropenia was significantly lower when irinotecan had been given in combination with oral alkalization drugs. CONCLUSIONS: These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely.

DOI： 10.1007/s00520-018-4367-y

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