Faculty Profiles - ZAMAMI Yoshito

Papers - ZAMAMI Yoshito

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Search for Therapeutic Agents for Cardiac Arrest Using a Drug Discovery Tool and Large-Scale Medical Information Database. Reviewed International journal

Yoshito Zamami, Takahiro Niimura, Toshihiro Koyama, Yuta Shigemi, Yuki Izawa-Ishizawa, Mizuki Morita, Ayako Ohshima, Keisaku Harada, Toru Imai, Hiromi Hagiwara, Naoto Okada, Mitsuhiro Goda, Kenshi Takechi, Masayuki Chuma, Yutaka Kondo, Koichiro Tsuchiya, Shiro Hinotsu, Mitsunobu R Kano, Keisuke Ishizawa

Frontiers in pharmacology 10 1257 - 1257 2019

Language：English Publishing type：Research paper (scientific journal)

The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using "TargetMine," a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to ≥10 patients and the objective variable being the "survival discharge." Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to ≥10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients.

DOI： 10.3389/fphar.2019.01257

Effect of the new preventive medicine on cisplatin-induced acute kidney injury

Goda Mitsuhiro, Hamano Hirofumi, Ikuta Kenji, Okada Naoto, Takechi Kenshi, Horinouchi Yuya, Ikeda Yasumasa, Ishizawa Keisuke, Saike Kazuhito, Kanda Masaya, Murai Yoichi, Yoshida Ami, Niimura Takahiro, Izawa-Ishizawa Yuki, Zamami Yoshito, Chuma Masayuki

Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 ( 0 ) 3 - P-076 2019

Language：Japanese Publisher：Japanese Pharmacological Society

<p>OBJECTIVE: Cisplatin (CDDP)-induced acute kidney injury (AKI) is highly expressed. Forced hydration and diuresis may partially prevent nephrotoxicity, but it is still difficult to completely prevent kidney injury, so establishment of a new preventive method is required. Therefore, in this study, we elected to candidates for preventive drugs of CDDP-induced AKI using big data analysis, and to verify the effectiveness of the drugs.</p><p>METHODS: Using FAERS (FDA Adverse Event Reporting System), existing drugs that may reduce CDDP-induced AKI were extracted. C57BL/6 mice were intraperitoneally administered with CDDP. Renal function was evaluated by serum creatinine and blood urea nitrogen. Histological damage in the cortex of kidney sections was scored. The effect of preventive drugs for CDDP-induced nephropathy was evaluated.</p><p>Results: The drug X was extracted a candidate drug suggesting the protective effect of CDDP-induced AKI by FAERS analysis. It was revealed that administration of the drug X significantly suppressed CDDP-induced AKI.</p><p>Conclusions: From the results of this study, it was suggested that existing pharmaceutical products elected by FAERS could be a preventive drug for CDDP-induced AKI.</p>

DOI： 10.1254/jpssuppl.92.0_3-P-076

Search for preventive drugs against anticancer drug-induced side effects using a large-scale medical information database

Zamami Yoshito, Izawa-Ishizawa Yuki, Ikeda Yasumasa, Kobayashi Daisuke, Shimazoe Takao, Ishizawa Keisuke, Kawajiri Takehiro, Niimura Takahiro, Goda Mitsuhiro, Okada Naoto, Hamano Hiroaki, Takechi Kenshi, Chuma Masayuki, Horinouchi Yuya

Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 2 - AS1-3 2019

Language：Japanese Publisher：Japanese Pharmacological Society

<p>Treatment outcomes of cancer patients have improved with progress in oncology medication therapy, but side effects caused by anticancer agents are becoming widespread. Side effects caused by anticancer drugs not only significantly lower the patient's QOL but also often lead to dose reduction or discontinuation of the anticancer drugs. Addressing these side effects is important for improving patient prognosis. Therefore, improvement of the quality of cancer therapy through the development of preventive drugs against anticancer drug-induced side effects is an urgent goal. In recent years, clinical research has been carried out in Japan using large-scale medical information sources such as disease/side effect databases, in order to accurately evaluate the effects of drug used in clinical practice. Research utilizing such a large-scale medical information database can cover various patient parameters and a wide range of observation areas. Therefore, this approach is suitable for conducting clinical research on rare diseases and low-frequency side effects. In this symposium, we will introduce research conducted using drug discovery tools and cell/animal experiments based on a large-scale medical information database to search for preventive agents against anticancer drug-induced side effects, as well as consider future prospects for this approach.</p>

DOI： 10.1254/jpssuppl.92.0_2-AS1-3

Iron metabolism abnormality in skeletal muscle atrophy associated with chronic renal failure

Horinouchi Yuya, Ikeda Yasumasa, Hamano Hirofumi, Imanishi Masaki, Fukushima Keijo, Goda Mitsuhiro, Takechi Kenshi, Miyamoto Licht, IZAWA-ISHIZAWA YUKI, Zamami Yoshito, Fujino Hiromichi, Ishizawa Keisuke, Tsuchiya Koichiro, Tamaki Toshiaki

Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 3-P-078 2019

Language：Japanese Publisher：Japanese Pharmacological Society

Introduction and aims: Skeletal muscle atrophy is often observed in chronic renal failure (CRF) patients. However, the molecular mechanism of skeletal muscle atrophy in CRF has remained unclear. Iron is an essential trace metal for all living organisms. On the other hand, excessive iron catalyzes the formation of highly toxic hydroxyl radicals via the Fenton reaction. The purpose of this study was to determine whether iron is involved in CRF-related skeletal muscle atrophy.

Methods: In this study, we divided 8-weeks-old C57BL/6J mice into two groups: vehicle-treated group (control mice) and adenine-injected group (CRF mice).

Results: Iron content was elevated in the skeletal muscle in CRF mice. Although the expression of divalent metal transporter 1 did not change, the expression of transferrin receptor and ferroportin were downregulated in the skeletal muscle in CRF mice. The expression of ferritin heavy chain and ferritin light chain were upregulated in the skeletal muscle in CRF mice. CRF mice showed increased oxidative stress in the skeletal muscles.

Conclusions: These results suggest that iron accumulation mediated oxidative stress has the potential to accelerate skeletal muscle atrophy in CRF.

DOI： 10.1254/jpssuppl.92.0_3-p-078

Effects of various 5-HT3 receptor antagonists on cisplatin-induced acute kidney injury

Murai Yoichi, Goda Mitsuhiro, Saike Kazuhito, Kanda Masaya, Yoshida Ami, Niimura Takahiro, Izawa-Ishizawa Yuki, Zamami Yoshito, Chuma Masayuki, Hamano Hirohumi, Okada Naoto, Takechi Kenshi, Horinouchi Yuya, Ikeda Yasumasa, Ishizawa Keisuke

Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 1-P-102 2019

Language：Japanese Publisher：Japanese Pharmacological Society

OBJECTIVE: Cisplatin (CDDP) is known to frequently cause nausea and vomiting, renal injury as a side effect. There are many kinds of 5-HT3 receptor antagonists, which are one of the basic antiemetic drugs for nausea and vomiting by cancer chemotherapy, such as the first generation ondansetron, granisetron, the second generation palonosetron. It is suggested that ondansetron may be a risk factor for the onset of CDDP-induced acute kidney injury (AKI). Therefore, in this study, the effect of various 5-HT3 receptor antagonists on CDDP-induced renal injury was examined.

METHODS: C57BL/6 mice were intraperitoneally administered with CDDP. Renal function was evaluated by serum creatinine and blood urea nitrogen. Histological damage in the cortex of HE‐stained kidney sections was scored. Various 5-HT3 receptor antagonists were administered 30 minutes before administration of CDDP.

RESULTS: CDDP-induced renal injury got significantly worse by pre-administration of ondansetron, but not by pretreatment of palonosetron compared with cisplatin alone group.

CONCLUSIONS: These results suggest that the second generation 5-HT3 receptor antagonist may have less effect on CDDP‐induced AKI than the first generation.

DOI： 10.1254/jpssuppl.92.0_1-p-102

Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed International journal

Hiroshi Onoue, Toshihiro Koyama, Yoshito Zamami, Hideharu Hagiya, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Yasuyoshi Ouchi, Mitsunobu R Kano

Journal of the American Geriatrics Society 66 ( 12 ) 2267 - 2273 2018.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To describe and examine trends in polypharmacy according to age in Japan from 2010 to 2016. DESIGN: Retrospective observational study. SETTING: Outpatient settings. PARTICIPANTS: Japanese individuals aged 20 and older. MEASUREMENTS: We analyzed pharmacy claims data that the Japanese Ministry of Health, Labor, and Welfare provided in the Survey of Medical Care Activities in Public Health Insurance from 2010 to 2016. The use of 5 or more oral prescription medications per month was defined as polypharmacy and of 10 or more as excessive polypharmacy. Regression analysis was used to estimate trends in polypharmacy with annual percentage changes. Using number of medications (polypharmacy vs excessive polypharmacy), trends in polypharmacy and crude and age-adjusted rates of polypharmacy per 1,000 persons were calculated according to year and age group (20-34, 35-49, 50-64, 65-79, ≥ 80). RESULTS: We analyzed 240 million pharmacy claims data. The age-adjusted monthly prevalence rate of polypharmacy increased from 85.2 to 93.8 per 1,000 persons per month and of excessive polypharmacy from 13.6 to 14.0 per 1,000 persons per month from 2010 to 2016 in the entire study population. The highest rate of polypharmacy (per 1,000 persons) was observed in 2016 in those aged 80 and older (326.8), followed by those aged 65 to 79 (167.3). The polypharmacy rate increased by 6.3% (95% confidence interval (CI)=4.0-8.7) per year from 2010 to 2012, then decreased by 0.7% (95% CI=-1.3-0.0) per year from 2012 to 2016. The rate of excessive polypharmacy increased by 4.5% (95% CI=1.1-8.0) per year from 2010 to 2013 and then decreased by 3.7% (95% CI=-6.7 to -0.6) per year from 2013 to 2016. CONCLUSION: The overall trend of polypharmacy in Japan increased during the study period, although the increase ceased in 2013 and then declined from 2013 to 2016. Policy changes in Japan might be responsible for some of the changes. J Am Geriatr Soc 66:2267-2273, 2018.

DOI： 10.1111/jgs.15569

Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels. Reviewed International journal

Shunsuke Ishida, Kenshi Takechi, Hiroshi Bando, Masaki Imanishi, Yoshito Zamami, Masayuki Chuma, Hiroaki Yanagawa, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Keisuke Ishizawa

Pharmacoepidemiology and drug safety 27 ( 12 ) 1379 - 1384 2018.12

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Drug side effects often lead to serious outcomes. Administration of second-generation antipsychotics has resulted in diabetic ketoacidosis and diabetic coma leading to death. Therefore, pharmacists are required to collect information on clinical test values, determine the appropriate test timing, and coordinate with doctors for further clinical laboratory orders, all of which are labor-intensive and time-intensive tasks. In this study, we developed a side effect-monitoring tool and aimed to clarify the influence and efficiency of monitoring side effects by using the tool in patients taking atypical antipsychotics in whom it is necessary to check clinical test values such as blood sugar levels. METHODS: We extracted clinical test values for patients treated with second-generation antipsychotics from electronic medical records. The test values are automatically displayed in the side effect grade classification specified by CTCAE ver. 4.0. A database was constructed using scripts to provide alerts for the timing of clinical testing. The pharmacist used this tool to confirm clinical test values for patients taking medication and requested the physician to inspect orders based on the appropriate test timings. RESULTS: The management tool reduced the pharmacists' effort in collecting information on patients' prescription status and test values. It enabled patients to undergo tests at the appropriate time according to the progression of glucose metabolism and allowed for easy monitoring of side effects. CONCLUSIONS: The results suggested that regardless of pharmacists' experience or skill, the introduction of this tool enables centralization of side effect monitoring and can contribute to proper drug use.

DOI： 10.1002/pds.4656

Trends in incidence and mortality of tuberculosis in Japan: a population-based study, 1997-2016. Reviewed International journal

H Hagiya, T Koyama, Yoshito Zamami, Y Minato, Y Tatebe, N Mikami, Y Teratani, A Ohshima, K Shinomiya, Y Kitamura, T Sendo, S Hinotsu, K Tomono, R M Kano

Epidemiology and infection 147 e38 2018.11

Language：English Publishing type：Research paper (scientific journal)

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

DOI： 10.1017/S095026881800290X

Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed

Onoue H, Koyama T, Zamami Y, Hagiya H, Tatebe Y, Mikami N, Shinomiya K, Kitamura Y, Hinotsu S, Sendo T, Ouchi Y, Kano MR

Journal of the American Geriatrics Society 66 ( 12 ) 2267 - 2273 2018.10

Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels. Reviewed

Ishida S, Takechi K, Bando H, Imanishi M, Zamami Y, Chuma M, Yanagawa H, Kirino Y, Nakamura T, Teraoka K, Ishizawa K

Pharmacoepidemiology and drug safety 27 ( 12 ) 1379 - 1384 2018.9

Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis. Reviewed International journal

Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Hirofumi Hamano, Yuki Izawa-Ishizawa, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki

Scientific reports 8 ( 1 ) 10858 - 10858 2018.7

Language：English Publishing type：Research paper (scientific journal)

Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis.

DOI： 10.1038/s41598-018-29008-2

The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease. Reviewed International journal

Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 33 ( 4 ) 586 - 597 2018.4

Language：English Publishing type：Research paper (scientific journal)

Background: Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear. Methods: We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations. We also used a mouse model of adenine-induced CKD. The CKD mice were divided into two groups: one was treated using AST-120 and the other received no treatment. We examined control mice, CKD mice, CKD mice treated using AST-120 and mice treated with IS via drinking water. Results: In the in vitro experiments using HepG2 cells, IS increased hepcidin expression in a dose-dependent manner. Silencing of the aryl hydrocarbon receptor (AhR) inhibited IS-induced hepcidin expression. Furthermore, IS induced oxidative stress and antioxidant drugs diminished IS-induced hepcidin expression. Adenine-induced CKD mice demonstrated an increase in hepcidin concentrations; this increase was reduced by AST-120, an oral adsorbent of the uremic toxin. CKD mice showed renal anemia, decreased plasma iron concentration, increased plasma ferritin and increased iron content in the spleen. Ferroportin was decreased in the duodenum and increased in the spleen. These changes were ameliorated by AST-120 treatment. Mice treated by direct IS administration showed hepatic hepcidin upregulation. Conclusions: IS affects iron metabolism in CKD by participating in hepcidin regulation via pathways that depend on AhR and oxidative stress.

DOI： 10.1093/ndt/gfx252

大規模医療情報データベース解析と基礎研究の融合による新規腎保護薬の探索 Reviewed

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

四国医学雑誌 74 ( 1-2 ) 82 - 83 2018.4

Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study. Reviewed International journal

Naoto Okada, Momoyo Azuma, Masaki Imanishi, Yoshito Zamami, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Masahiro Abe, Keisuke Ishizawa

Clinical therapeutics 40 ( 2 ) 252 - 260 2018.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB-induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients. METHODS: Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24). FINDINGS: Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB-induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB-induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019-0.47]). IMPLICATIONS: This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.

DOI： 10.1016/j.clinthera.2017.12.006

Trends in the medication reviews of community pharmacies in Japan: a nationwide retrospective study. Reviewed International journal

Toshihiro Koyama, Hiroshi Onoue, Ayako Ohshima, Yuri Tanaka, Yasuhisa Tatebe, Yoshito Zamami, Kazuaki Shinomiya, Yoshihisa Kitamura

International journal of clinical pharmacy 40 ( 1 ) 101 - 108 2018.2

Language：English Publishing type：Research paper (scientific journal)

Background The trends in medication reviews made by community pharmacies in Japan are currently unknown. Objective We aimed to comprehensively describe the national trends in medication reviews in Japan's community pharmacies in the backdrop of the country's ageing population. Setting Community pharmacies in Japan. Methods We analysed national health insurance claims data for 2010-2015. These data were provided by the Ministry of Health, Labour and Welfare as part of the Survey of Medical Care Activities in Public Health Insurance. Main outcome measures The national trends in community pharmacy visits involving medicine dispensing and medication reviews that involve consultations with a physician. Results Among the 365 million pharmacy visits for 2010-2015, we identified 373,429 medication reviews accompanied by consultations with a physician. The pharmacy visit rate per 1000 population increased from 427.2 in 2010 to 483.7 in 2015. Medication reviews also increased from 407 per million pharmacy visits in 2010 to 1445 in 2015. Among the 373,429 medication reviews during the study period, the prescription was changed through collaboration with a physician 338,982 times (90.4%). The proportion of medication review acceptance increased from 80.6% in 2010 to 94.8% in 2015. The prescription change rate was higher among older patients than among younger ones. Conclusions Medication reviews by community pharmacists involving consultations with a physician increased in Japan from 2010 to 2015, as did prescription changes following these reviews.

DOI： 10.1007/s11096-017-0559-7

Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit. Reviewed International journal

Takahiro Niimura, Yoshito Zamami, Toru Imai, Kanako Nagao, Masafumi Kayano, Hidenori Sagara, Mitsuhiro Goda, Naoto Okada, Masayuki Chuma, Kenshi Takechi, Masaki Imanishi, Toshihiro Koyama, Tadashi Koga, Hironori Nakura, Toshiaki Sendo, Keisuke Ishizawa

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 21 ( 1 ) 54 - 59 2018

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis recommend de-escalation of treatment after identification of the causative pathogen, adherence to this practice remain unknown. The objective of this study was to evaluate the benefits of de-escalating treatment for sepsis patients at an advanced critical care and emergency medical centre. METHODS: Based on electronic patient information, 85 patients who were transported to the centre by ambulance, and diagnosed with sepsis between January 2008 and September 2013 were enrolled and evaluated. Patients were divided into two groups with and without de-escalation, and comparisons were conducted for several variables, including length of hospital stay, and length of antibiotic administration. Two types of subgroup analysis were conducted between patients with septic shock or positive blood cultures. Statistical analysis was conducted using chi-square and Mann-Whitney U tests. RESULTS: The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration. CONCLUSIONS: The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

DOI： 10.29173/jpps29737

Administration of Kampo medicine through a tube at an advanced critical care center. Reviewed

Takahiro Niimura, Yoshito Zamami, Toru Imai, Tsuyoshi Ito, Hidenori Sagara, Hichiya Hiroyuki, Satoru Esumi, Kenshi Takechi, Masaki Imanishi, Toshihiro Koyama, Manabu Amano, Naomi Kurata, Yoshihisa Kitamura, Hironori Nakura, Toshiaki Sendo, Keisuke Ishizawa

The journal of medical investigation : JMI 65 ( 1.2 ) 32 - 36 2018

Language：English Publishing type：Research paper (scientific journal)

n emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method. J. Med. Invest. 65:32-36, February, 2018.

DOI： 10.2152/jmi.65.32

Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation. Reviewed International journal

Masaki Imanishi, Yuki Izawa-Ishizawa, Takumi Sakurada, Yusuke Kohara, Yuya Horinouchi, Eriko Sairyo, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Keijo Fukushima, Yasumasa Ikeda, Hiromichi Fujino, Masanori Yoshizumi, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa

Pharmacology 102 ( 5-6 ) 287 - 299 2018

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIMS: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. METHODS: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. RESULTS: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. CONCLUSION: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.

DOI： 10.1159/000492577

Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit. Reviewed

Niimura T, Zamami Y, Imai T, Nagao K, Kayano M, Sagara H, Goda M, Okada N, Chuma M, Takechi K, Imanishi M, Koyama T, Koga T, Nakura H, Sendo T, Ishizawa K

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 21 ( 1 ) 54 - 59 2018

Language：English Publishing type：Research paper (scientific journal)

The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration.

DOI： 10.18433/jpps29737

Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation Reviewed

Zamami Y, Kouno Y, Niimura T, Chuma M, Imai T, Mitsui M, Koyama T, Kayano M, Okada N, Hamano H, Goda M, Imanishi M, Takechi K, Horinouchi Y, Kondo Y, Yanagawa H, Kitamura Y, Sendo T, Ujike Y, Ishizawa K

Pharmazie 73 ( 12 ) 740 - 743 2018

Publishing type：Research paper (scientific journal)

A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium.

DOI： 10.1691/ph.2018.8711

Other Link： http://orcid.org/0000-0002-5755-283X

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