Congenital abnormalities in Japanese patients with Menkes disease.

PubMed

Gu, Yan-Hong; Kodama, Hiroko; Kato, Tadaaki

2012-10-01

Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born infants with MNK is 2.8 per million live births in Japan. The aim of this study was to observe congenital malformations (CMs) in MNK patients. Subjects comprised 35 Japanese male patients with classical MNK who received copper histidine treatment. Patient clinical data were obtained anonymously from medical records or medical record summaries by pediatrician's retrospective review through a survey. We observed 21 different CMs in 14 patients. Eight of these had a single CM, while six had multiple CMs. The most frequent CM was higher arched palate with other CMs found in five patients. There was no relationship between CMs and mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also significantly lower in MNK patients with CMs (P<0.05), compared to those without CMs, even though there was no significant difference of age onset, age at diagnosis and age at start of treatment with copper histidine between both groups of patients. Sudden death occurred in three MNK patients with CMs only: two with congenital heart disease, and one with microphallus. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Attitudes towards cross-border reproductive care among infertile Japanese patients.

PubMed

Hibino, Yuri; Shimazono, Yosuke; Kambayashi, Yasuhiro; Hitomi, Yoshiaki; Nakamura, Hiroyuki

2013-11-01

The attitudes towards cross-border reproductive care (CBRC) held by infertile Japanese patients have not been explored. The objective of the present study was to examine interest levels, preferred destinations, motivations, and sources of information related to CBRC. Our findings provide a general outline of CBRC and the future of reproduction and assisted reproductive technology (ART) in Japan. The study used a cross-sectional design. Data were collected from 2,007 infertile Japanese patients from 65 accredited ART clinics in Japan (response rate, 27.4 %) via anonymous questionnaires. Most of the infertile Japanese patients who responded denied using CBRC. However, by group, 171 (8.5 %) patients in non-donor in vitro fertilization, 150 (7.5 %) in egg donation, 145 (7.2 %) in pre-implantation genetic diagnosis, and 129 (6.4 %) in surrogacy said that, depending on the situation, they might travel abroad in the future. Older respondents were more likely to express an intention to travel overseas for egg donation in the future. The most popular destination for CBRC was the United States. Popular reasons for interest in CBRC among those considering or planning using this approach to third-party reproduction were that egg donation or surrogacy was unavailable or that obtaining ethical approval takes too long in Japan, whereas these processes are legal and affordable overseas. However, high cost was the most common reason for hesitancy regarding CBRC. Among the participants who were considering or planning to travel abroad for this purpose, TV, medical agencies, print media, and message boards on websites were popular sources of information, whereas doctors, friends, and patient self-help groups were not. Although CBRC among infertile Japanese patients is not at present common, the demand for and use of this approach may increase in the future in the context of the increasingly aging population. Lack of regulation and unavailability of third-party reproduction is a

[Quality of life in patients with Japanese cedar pollinosis: using the SF-8 health status questionnaire (Japanese version)].

PubMed

Fujii, Tsukasa; Ogino, Satoshi; Arimoto, Hiroe; Irifune, Morihiro; Iwata, Nobuko; Ookawachi, Ichiro; Kikumori, Hiroshi; Seo, Ritsu; Takeda, Mariko; Tamaki, Akiko; Baba, Kenji; Nose, Michihiro

2006-10-01

The number of patients with Japanese cedar pollinosis (JCP) is increasing, and now, has extended up to about 15% of the Japanese. It is reported that the QOL is an important outcome in the JCP treatment. This study aimed to evaluate the QOL in patients with JCP by means of the SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) were questioned, and 204 patients without any treatments in this season were engaged in this study as subjects. In this study, the QOL scores were evaluated using the SF-8. This is an 8-item version of the SF-36 that yields a comparable 8-dimension health profile and comparable estimates of summary scores for the physical and mental components of health. The QOL score depressed in the patients with JCP compared with healthy subjects (Japanese national norms). Both Mental Component Score (MCS) and Physical Component Score (PCS) scores decreased more in females than in males. In females, MCS were significantly lower than national norms. The older the patients were, the lower PCS scores were showed. The severity of nasal symptoms influenced the PCS scores. These results showed the tendency similar to the early studies using SF-36 questionnaire. The sensitivity of SF-8 in the individual is not better than that of other specific QOL questionnaires, but SF-8 can be answered in a short time compared with other questionnaires including SF-36. We suggested that SF-8 become a useful questionnaire in the future.

Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations.

PubMed

Okabe, Masahiro; Yamaguchi, Hiroki; Usuki, Kensuke; Kobayashi, Yutaka; Kawata, Eri; Kuroda, Junya; Kimura, Shinya; Tajika, Kenji; Gomi, Seiji; Arima, Nobuyoshi; Mori, Sinichiro; Ito, Shigeki; Koizumi, Masayuki; Ito, Yoshikazu; Wakita, Satoshi; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Dan, Kazuo; Inokuchi, Koiti

2016-01-01

The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients. Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

PubMed

Yanagihara, Katsunori; Watanabe, Akira; Aoki, Nobuki; Matsumoto, Tetsuya; Yoshida, Masaki; Sato, Junko; Wakamura, Tomotaro; Sunakawa, Keisuke; Kadota, Junichi; Kiyota, Hiroshi; Iwata, Satoshi; Kaku, Mitsuo; Hanaki, Hideaki; Ohsaki, Yoshinobu; Fujiuchi, Satoru; Takahashi, Manabu; Takeuchi, Kenichi; Takeda, Hiroaki; Ikeda, Hideki; Miki, Makoto; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Nishiya, Hajime; Kawakami, Sayoko; Morino, Eriko; Takasaki, Jin; Mezaki, Kazuhisa; Chonabayashi, Naohiko; Tanaka, Chie; Sugiura, Hideko; Goto, Hajime; Saraya, Takeshi; Kurai, Daisuke; Katono, Yasuhiro; Inose, Rika; Niki, Yoshihito; Takuma, Takahiro; Kudo, Makoto; Ehara, Shigeru; Sato, Yoshimi; Tsukada, Hiroki; Watabe, Nobuei; Honma, Yasuo; Mikamo, Hiroshige; Yamagishi, Yuka; Nakamura, Atsushi; Ohashi, Minoru; Seki, Masafumi; Hamaguchi, Shigeto; Toyokawa, Masahiro; Fujikawa, Yasunori; Mitsuno, Noriko; Ukimura, Akira; Miyara, Takayuki; Nakamura, Takahito; Mikasa, Keiichi; Kasahara, Kei; Ui, Koji; Fukuda, Saori; Nakamura, Akihiro; Morimura, Mika; Yamashita, Mikio; Takesue, Yoshio; Wada, Yasunao; Sugimoto, Keisuke; Kusano, Nobuchika; Nose, Motoko; Mihara, Eiichirou; Kuwabara, Masao; Doi, Masao; Watanabe, Yaeko; Tokuyasu, Hirokazu; Hino, Satoshi; Negayama, Kiyoshi; Mukae, Hiroshi; Kawanami, Toshinori; Ota, Toshiyuki; Fujita, Masaki; Honda, Junichi; Hiramatsu, Kazufumi; Aoki, Yosuke; Fukuoka, Mami; Magarifuchi, Hiroki; Nagasawa, Zenzo; Kaku, Norihito; Fujita, Jiro; Higa, Futoshi; Tateyama, Masao

2017-09-01

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 37.2% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

PubMed

Morita, Shigemichi; Takahashi, Toshiya; Yoshida, Yasushi; Yokota, Naohisa

2016-04-01

Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed. In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap. The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P < 0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges. The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.

The phenotype and clinical course of Japanese Fanconi Anaemia infants is influenced by patient, but not maternal ALDH2 genotype.

PubMed

Yabe, Miharu; Yabe, Hiromasa; Morimoto, Tsuyoshi; Fukumura, Akiko; Ohtsubo, Keisuke; Koike, Takashi; Yoshida, Kenichi; Ogawa, Seishi; Ito, Etsuro; Okuno, Yusuke; Muramatsu, Hideki; Kojima, Seiji; Matsuo, Keitaro; Hira, Asuka; Takata, Minoru

2016-11-01

Studies using Fanconi anaemia (FA) mutant mouse models suggested that the combination of a defective FA pathway and aldehyde dehydrogenase-2 (ALDH2) dysfunction could provoke bone marrow failure, leukaemia and developmental defects, and that both maternal and fetal aldehyde detoxification are crucial to protect the developing embryo from DNA damage. We studied the ALDH2 genotypes of 35 Japanese FA patients and their mothers. We found that a normal maternal ALDH2 allele was not essential for fetal development of ALDH2-deficient patients, and none of the post-natal clinical parameters were clearly affected by the maternal ALDH2 genotype in these patients. © 2016 John Wiley & Sons Ltd.

Hla-B genotype in Japanese patients with Crohn's disease.

PubMed

Kinouchi, Yoshitaka; Matsumoto, Keisuke; Negoro, Kenichi; Takagi, Sho; Takahashi, Seiichi; Hiwatashi, Nobuo; Shimosegawa, Tooru

2003-10-01

The HLA-B gene is one of the susceptibility genes for inflammatory bowel disease. Previous association studies of HLA-B showed several associated alleles and haplotypes of HLA-B in patients with ulcerative colitis, and among the associated alleles HLA-B*52 is well known to be strongly associated with ulcerative colitis in Japanese patients. However, there are no convincing reports about HLA-B including the B*52 allele in patients with Crohn's disease. The purpose of this study was to determine if HLA-B, especially the B*52 allele, confers susceptibility to Crohn's disease or determines the disease phenotype of Crohn's disease. A total of 195 patients with Crohn's disease (49 ileitis, 106 ileocolitis, 34 colitis, 6 uncertain) and 185 healthy controls were studied in this case-controlled study. All patients and healthy controls were Japanese. Genotyping of the HLA-B gene was performed by a polymerase chain reaction, sequence-specific primer that can classify the gene into 23 allele groups. Allele frequencies were compared between patients with Crohn's disease and healthy controls with chi-squared test using a 2 x 2 contingency table. P value was corrected by the number of allele groups (n = 23) observed in the Japanese population or the number of clinical subgroups. Corrected P values of <0.05 were considered to be statistically significant. Before the correction for multiple testing, B*4001 and B*44 were associated with patients with Crohn's disease, positively and negatively, respectively. However, after the correction there were no significant differences in any HLA-B alleles between patients with Crohn's disease and healthy controls. In the subgroup analysis according to clinical phenotypes (disease location, anal lesion, age at diagnosis, need for surgery), none of the HLA-B alleles except B*52 showed any disease phenotype-genotype associations. The allele frequency of B*52 in the colitis type (16.2 percent; corrected P = 0.011) was significantly higher than

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections.

PubMed

Aikawa, Naoki; Kusachi, Shinya; Mikamo, Hiroshige; Takesue, Yoshio; Watanabe, Shinichi; Tanaka, Yoshiyuki; Morita, Akiko; Tsumori, Keiko; Kato, Yoshiaki; Yoshinari, Tomoko

2013-06-01

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia.

PubMed

Fujino, Haruo; Sumiyoshi, Chika; Sumiyoshi, Tomiki; Yasuda, Yuka; Yamamori, Hidenaga; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Higuchi, Arisa; Hibi, Yumiko; Matsuura, Yukako; Hashimoto, Ryota; Takeda, Masatoshi; Imura, Osamu

2014-07-01

Patients with schizophrenia have been reported to perform worse than non-schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls. Performance on the WAIS-III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects. All IQ scores and four indices from the WAIS-III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = -1.70, d = 1.55), Digit Symbol Coding (z = -1.84, d = 1.88), and Symbol Search (z = -1.85, d = 1.77) were profoundly impaired relative to the healthy controls. These results indicate that the pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese patients are similar to those previously reported in English-speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Characteristics of MUTYH variants in Japanese colorectal polyposis patients.

PubMed

Takao, Misato; Yamaguchi, Tatsuro; Eguchi, Hidetaka; Tada, Yuhki; Kohda, Masakazu; Koizumi, Koichi; Horiguchi, Shin-Ichiro; Okazaki, Yasushi; Ishida, Hideyuki

2018-06-01

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype-phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis. After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH. Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants 'pathogenic' were lacking. Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

Risk factors for coronary artery calcification in Japanese patients.

PubMed

Shikada, Tomoki; Washio, Masakazu; Nishizaki, Akiko; Kakino, Takamori; Ooe, Kensuke; Ishibashi, Yuuji; Sagara, Shuuichirou; Morishige, Kunio; Tashiro, Hideki

2015-07-01

Because the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population. Study subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors. Old age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios. In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Safety and Effectiveness of Mirabegron in Patients with Overactive Bladder in a Real-World Clinical Setting: A Japanese Post-Marketing Study.

PubMed

Nozawa, Yumiko; Kato, Daisuke; Tabuchi, Hiromi; Kuroishi, Kentarou

2018-05-01

To provide real-world data on Japanese patients with overactive bladder (OAB) initiating treatment with the β 3 -adrenoceptor agonist, mirabegron. This study examined prescribing patterns, adverse drug reaction (ADR) incidence, and treatment effectiveness. Full medical histories, including prior/concomitant drug use, were collected before initiating mirabegron treatment. After 12 weeks mirabegron, physicians assessed ADR incidence and treatment effectiveness. Residual urine volume was assessed and patients completed the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score-Quality of Life (I-PSS QoL) surveys at Baseline and 12 weeks. Data were collected between April 2012 and July 2014. Of 9795 OAB patients (46.8% male; 80.8% ≥65 years), 71.7% had coexisting disease [notably benign prostatic hyperplasia (BPH, 32.4%), hypertension (31.9%), and diabetes mellitus (9.4%)] and 53.4% reported concomitant drug use (27.8% α 1 -antagonists, 6.3% anticholinergics). The incidence of total ADRs was 6.07% [including constipation (0.97%), thirst (0.47%), and dysuria (0.44%)], of serious ADRs, 0.21%, of cardiovascular ADRs, 0.48% and of urinary retention, 0.31%. Incidence of total ADRs in patients with concomitant cardiovascular disease was 10.09% and of those related to urinary retention in men with untreated BPH, 0.88%. After 12 weeks treatment, physicians judged mirabegron as "effective" in 80.7% of patients, 63.6% of patients achieved the three-point minimal clinically important change from Baseline in the mean OABSS, and the I-PSS QoL decreased significantly from Baseline (-2.1 ± 1.77; P < 0.001). In the clinical setting, mirabegron is well tolerated, with no unanticipated ADRs, and is an effective treatment for Japanese patients with OAB. © 2016 Astellas Pharma Inc. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd.

Clinical behavior of Japanese community pharmacists for preventing prescription drug overdose.

PubMed

Shimane, Takuya; Matsumoto, Toshihiko; Wada, Kiyoshi

2015-04-01

Prescription drug abuse, including benzodiazepines, is a growing health problem in Japan. This study examined the community pharmacist's clinical behavior regarding patients who overdose on prescribed drugs, and explored the possibility of overdose prevention by community pharmacists. We surveyed all registered community pharmacies with dispensing functions (n = 1867) in the Saitama Pharmaceutical Association. An anonymous self-administered questionnaire was mailed to each pharmacy. Respondents were asked about clinical behavior such as medication counseling and referral to the prescriber if prescription drug overdose was identified. Among respondents, 26% of community pharmacists reported clinical experience of working with patients who overdosed on prescribed drugs in the previous year. Half of respondents evaluated their practice such as medication counseling and referral to the prescriber as 'good'. On multivariate analysis, a 'poor' self-evaluation of referral to the prescriber was significantly associated with the following perceptions: 'insufficient confidence in communication with prescribers' (odds ratio [OR], 2.7; 95% confidence interval [95%CI]: 1.4-5.3), and 'to avoid trouble with prescribers' (OR, 1.7; 95%CI: 1.0-2.7). Japanese community pharmacists could prevent prescription drug abuse in their practice, but the pharmacists who have insufficient confidence in communication with prescribers and who are afraid of trouble with a prescriber, reported poor self-evaluation for referral to the prescribers. All prescribers should understand the importance of referral by community pharmacists, to assist community pharmacists in playing a critical role in prevention of prescription drug abuse. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

PubMed

Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

2014-01-01

The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

[Clinical features in a Japanese patient with autosomal dominant lateral temporal epilepsy having LGI1 mutation].

PubMed

Fujita, Youshi; Ikeda, Akio; Kadono, Kentaro; Kawamata, Jun; Tomimoto, Hidekazu; Fukuyama, Hidenao; Takahashi, Ryosuke

2009-04-01

We described a clinical feature of autosomal dominant lateral temporal epilepsy (ADLTE) in a Japanese patient having LGI1 mutation. The patient was a 27-year-old woman who had her first seizure at the age of 10 years, a nocturnal generalized seizure. She then had partial seizures manifesting auditory symptoms with or without anxiety, panic attack, déjà vu, sensory aphasia and visual symptoms. Repeated EEGs were normal. Brain MRI showed small left superior temporal gyrus. 18F-deoxyglucose positron emission tomography (PDG-PET) demonstrated glucose hypometabolism in the left lateral temporal lobe. Sequencing of the LGI1 revealed a single base substitution in exon 8 (1642C-->T) causing missense mutation at residue 473 of the LGI1 protein (S473 L). When one demonstrates ictal symptoms arising from the lateral temporal to occipital area with psychotic symptoms, ADLTE should be suspected and a detailed family history is warranted.

Screening for major depressive episodes in Japanese patients with epilepsy: validation and translation of the Japanese version of Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

PubMed

Tadokoro, Yukari; Oshima, Tomohiro; Fukuchi, Toshihiko; Kanner, Andres M; Kanemoto, Kousuke

2012-09-01

We validated and translated into Japanese the English version of the screening instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to identify major depressive episodes in patients with epilepsy. A total of 159 Japanese subjects with epilepsy underwent a psychiatric structured interview with the Japanese version of the Mini International Neuropsychiatric Interview (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J). Twelve participants met the M.I.N.I.-J criteria of current major depressive episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's alpha coefficient was 0.83 and a cut-off score greater than 16 provided a sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of 0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for major depressive episodes in epilepsy patients. Routine use of this brief and self-administered instrument in busy clinical settings will likely improve management of depression in Japanese individuals with epilepsy. Copyright © 2012 Elsevier Inc. All rights reserved.

Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2012-01-01

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Long-term safety and effectiveness of brexpiprazole in Japanese patients with schizophrenia: A 52-week, open-label study.

PubMed

Ishigooka, Jun; Iwashita, Shuichi; Tadori, Yoshihiro

2018-06-01

This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia. This 52-week, open-label, flexible-dose (1-4 mg/day) study included patients with schizophrenia who continued treatment from a short-term randomized placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who switched from other antipsychotics. A total of 282 patients (184 de novo and 98 rolled over from short-term trial) entered the 52-week treatment with brexpiprazole, and 150 (53.2%) patients completed the week-52 assessment. Treatment-emergent adverse events (TEAE) were experienced by 235/281 patients (83.6%), and TEAE reported by ≥10% of all patients were nasopharyngitis (23.1%) and worsening of schizophrenia (22.4%). During the study, most of the TEAE were mild or moderate in severity, and there were no deaths, and no clinically meaningful mean changes in laboratory values, vital signs, or electrocardiogram parameters. Mean scores for the Positive and Negative Syndrome Scale total and Clinical Global Impression-Severity remained stable until week 52. Brexpiprazole was generally safe and well tolerated and maintained therapeutic effects in the long-term treatment of Japanese patients with schizophrenia. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Japanese Encephalitis Virus in Meningitis Patients, Japan

PubMed Central

Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

2005-01-01

Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008: the first large-scale study from the Cancer Registration Committee of the Japanese Urological Association.

PubMed

Miki, Tsuneharu; Kamoi, Kazumi; Fujimoto, Hiroyuki; Kanayama, Hiro-omi; Ohyama, Chikara; Suzuki, Kazuhiro; Nishiyama, Hiroyuki; Eto, Masatoshi; Naito, Seiji; Fukumori, Tomoharu; Kubota, Yoshinobu; Takahashi, Satoru; Mikami, Kazuya; Homma, Yukio

2014-08-01

To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association. Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes. We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively. The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment. © 2014 The Japanese Urological Association.

Factors Affecting Professional Autonomy of Japanese Nurses Caring for Culturally and Linguistically Diverse Patients in a Hospital Setting in Japan.

PubMed

Kuwano, Noriko; Fukuda, Hiromi; Murashima, Sachiyo

2016-11-01

The study aimed to analyze the professional autonomy of Japanese nurses when caring for non-Japanese patients and to identify its contributing factors. A descriptive cross-sectional design was used. Participants included 238 clinical nurses working at 27 hospitals in Japan. The Intercultural Sensitivity Scale (Chen and Starosta), and the Scale for Professional Autonomy in Nursing (Kikuchi and Harada) were used to measure intercultural sensitivity and professional autonomy. Stepwise multiple regression analysis was used to identify the most significant factors affecting professional autonomy. Professional autonomy of Japanese nurses caring for non-Japanese patients was significantly lower than when caring for Japanese patients (142.84 vs. 172.85; p < .001). Contributing factors were intercultural sensitivity (p < .001), length of nurse experience (p < .05), and availability of interpretation service (p < .05). Incorporating transcultural nursing content into training programs in schools and hospitals could enhance professional autonomy of Japanese nurses by promoting intercultural sensitivity. © The Author(s) 2015.

Pathophysiology and Japanese clinical characteristics in Marfan syndrome.

PubMed

Fujita, Daishi; Takeda, Norifumi; Imai, Yasushi; Inuzuka, Ryo; Komuro, Issei; Hirata, Yasunobu

2014-08-01

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome. © 2014 Japan Pediatric Society.

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study.

PubMed

Yasumoto, Sawa; Ohtsuka, Yoko; Sato, Katsuaki; Kurata, Atsuyo; Numachi, Yotaro; Shimizu, Masahiro

2018-05-31

To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

PubMed

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

PubMed

Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

2016-09-01

The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

The seventh nationwide epidemiological survey for chronic pancreatitis in Japan: clinical significance of smoking habit in Japanese patients.

PubMed

Hirota, Morihisa; Shimosegawa, Tooru; Masamune, Atsushi; Kikuta, Kazuhiro; Kume, Kiyoshi; Hamada, Shin; Kanno, Atsushi; Kimura, Kenji; Tsuji, Ichiro; Kuriyama, Shinichi

2014-01-01

A nationwide survey was conducted to clarify the epidemiological features of patients with chronic pancreatitis (CP) in Japan. In the first survey, both the prevalence and the incidence of CP in 2011 were estimated. In the second survey, the clinicoepidemiological features of the patients were clarified by mailed questionnaires. Patients were diagnosed by the Japanese diagnostic criteria for chronic pancreatitis 2009. The estimated annual prevalence and incidence of CP in 2011 were 52.4/100,000 and 14.0/100,000, respectively. The sex ratio (male/female) of patients was 4.6, with a mean age of 62.3 years. Alcoholic (67.5%) was the most common and idiopathic (20.0%) was the second most common cause of CP. Comorbidity with diabetes mellitus (DM) and pancreatic calcifications (PC) occurred more frequent in ever smokers independently of their drinking status. Among patients without drinking habit, the incidences of DM and PC were significantly higher in ever smokers than in never smokers. The multiple logistic regression analysis revealed smoking was an independent factor of DM and PC in CP patients: DM, Odds ratio (OR) 1.644, 95% confidence interval (CI) 1.202 to 2.247 (P = 0.002): PC, OR 2.010, 95% CI 1.458 to 2.773 (P < 0.001). On the other hand, smoking was not identified as an independent factor for the appearance of abdominal pain by this analysis. The prevalence of Japanese patients with CP has been increasing. Smoking was identified as an independent factor related to DM and PC in Japanese CP patients. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Memantine in Japanese patients with moderate to severe Alzheimer's disease: meta-analysis of multiple-index responder analyses.

PubMed

Okuizumi, Kaoru; Kamata, Teruyoshi; Matsui, Daiju; Saito, Kengo; Matsumoto, Takuyuki; Fukuchi, Yoshikazu

2018-04-01

Responder analyses assessing clinical worsening have attempted to clarify clinically meaningful drug efficacy enhancements in patients with Alzheimer's disease (AD). This was a meta-analysis of two multicenter, randomized, double-blind, parallel-group, 24-week studies of 633 Japanese patients with moderate to severe AD receiving memantine 20 mg/day (n = 318) or placebo (n = 315). The clinical trial registration number is UMIN000026013. Overall odds ratios (OR) for a reduced likelihood of clinical worsening (memantine versus placebo) were statistically significant on the following individual and combined rating scales: Severe Impairment Battery-Japanese version (SIB-J, OR 0.52; 95% CI: 0.37, 0.73; p = 0.0001); Behavioral Pathology in AD Rating Scale (BEHAVE-AD, OR 0.53; 95% CI: 0.37, 0.75; p = 0.0003); and SIB-J + Clinician's Interview-Based Impression of Change-plus-Japanese version (SIB-J + CIBIC-plus-J; OR 0.53; 95% CI: 0.37, 0.77; p = 0.0009). A significantly reduced risk of triple worsening was evident in the memantine versus placebo group on the combined SIB-J + CIBIC-plus-J + BEHAVE-AD rating scales (OR 0.38; 95% CI: 0.22, 0.65; p = 0.0003). Memantine is a viable treatment option for patients with AD presenting not only with cognitive impairment, but also with a broader range of symptoms, including the behavioral and psychological symptoms of dementia.

Clinical and economic burdens experienced by patients with painful diabetic peripheral neuropathy: An observational study using a Japanese claims database.

PubMed

Ebata-Kogure, Nozomi; Nozawa, Kazutaka; Murakami, Aya; Toyoda, Tetsumi; Haga, Yuri; Fujii, Koichi

2017-01-01

Diabetic peripheral neuropathy (DPN) may often be painful. Despite the high prevalence of painful DPN (pDPN) among patients with diabetes mellitus (DM), understanding of its clinical and economic burden is limited. This study aimed to describe the clinical and economic burdens faced by patients with pDPN in Japan, and compared them with those experienced by patients with DPN but without painful symptoms (non-pDPN). This retrospective, observational study used data from a large-scale, hospital-based Japanese claims database collected from April 2008 to June 2015. Comorbidities, clinical departments visited, length of hospital stay, and medical costs for the period of ± 6 months from the diagnosis of pDPN or non-pDPN were described for each group. Glycemic control status was examined for each group for patients with glycated hemoglobin data. The data of 8,740 patients with pDPN (mean age 70.0 years, 53.4% male) and 12,592 patients with non-pDPN (mean age 67.7 years, 55.7% male) were analyzed. Patients with pDPN had more comorbidities than patients with non-pDPN; 48.7% and 30.9% of patients in the respective groups had 20 or more comorbidities. The median length of hospital stay was 5 days longer in patients with pDPN. The median total medical costs were higher in patients with pDPN (\\517,762) than in patients with non-pDPN (\\359,909). Patients with pDPN spent higher median costs for medications, but the costs for glycemic control drugs were similar in both groups. For 3,372 patients with glycated hemoglobin data, glycemic control was similar between the two groups. Patients with pDPN experienced greater clinical and economic burdens than patients with non-pDPN, suggesting that patients who develop pDPN may suffer not only from the complications of DM and pain, but also from other comorbid disorders.

Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis

PubMed Central

Iijima, Hirotaka; Fukutani, Naoto; Fukumoto, Takahiko; Uritani, Daisuke; Kaneda, Eishi; Ota, Kazuo; Kuroki, Hiroshi; Matsuda, Shuichi

2015-01-01

Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. PMID:26017348

Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients

PubMed Central

Yamaguchi, Tatsuro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Hinoi, Takao; Inoue, Yasuhiro; Ishida, Fumio; Kanemitsu, Yukihide; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Watanabe, Toshiaki; Sugihara, Kenichi

2016-01-01

Objective The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients. Methods This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study. Results In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively. Conclusions Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population. PMID:26819281

[Neuromuscular blocking effects of Org 9426 (rocuronium bromide); a comparative study with vecuronium bromide in Japanese patients].

PubMed

Shingu, Koh; Masuzawa, Munehiro; Omote, Keiichi; Namiki, Akiyoshi; Kikuchi, Hirosato; Kawamada, Miwako; Sato, Shigehito; Kimura, Tomomasa; Hatano, Norio; Nakatsuka, Hideki; Morita, Kiyoshi; Hara, Tetsuya; Kanmura, Yuichi; Takeda, Junzo

2006-09-01

Efficacy and safety of Org 9426 were compared with those of vecuronium bromide in Japanese patients. We studied 88 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of 0.6 mg x kg(-1), 0.9 mg x kg(-1) of Org 9426 or 0.1mg x kg(-1) of vecuronium. Following an intubation dose, patients received maintenance doses of 0.1, 0.15 or 0.2 mg x kg(-1) of Org 9426 or 0.025 mg x kg(-1) of vecuronium. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. The onset times of the 0.6 and 0.9 mg x kg(-1) of Org 9426 groups were 84.6 and 77.1 sec respectively, which showed statistical difference between the onset time of 0.1 mg x kg(-1) of vecuronium, 125.7 sec. The intubation condition was similar among three treatment groups. The clinical durations of 0.6 and 0.9 mg x kg(-1) of Org 9426 and 0.1 mg x kg(-1) of vecuronium were 53.4, 73.4 and 59.9 min, respectively. Clinical duration and spontaneous recovery time of maintenance dose of 0.15 mg x kg(-1) of Org 9426 were similar to those of 0.025 mg x kg(-1) of vecuronium. Org 9426 showed more rapid onset time than that of vecuronium and similar clinical duration and recovery times to those of vecuronium in Japanese patients.

Mitochondrial haplogroups associated with Japanese centenarians, Alzheimer's patients, Parkinson's patients, type 2 diabetic patients and healthy non-obese young males.

PubMed

Takasaki, Shigeru

2009-07-01

The relationships between five classes of Japanese people (i.e., 96 centenarians, 96 Alzheimer's disease (AD) patients, 96 Parkinson's disease (PD) patients, 96 type 2 diabetic (T2D) patients, and 96 healthy non-obese young males) and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function (RBF) network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups: Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4c1, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8a1, G, D4, and F1; and Japanese healthy non-obese young males- D4g and D4b1b. From the points of common haplogroups among the five classes, the centenarians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians (over 105 years old) recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person's mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

PubMed

Nishida, Osamu; Ogura, Hiroshi; Egi, Moritoki; Fujishima, Seitaro; Hayashi, Yoshiro; Iba, Toshiaki; Imaizumi, Hitoshi; Inoue, Shigeaki; Kakihana, Yasuyuki; Kotani, Joji; Kushimoto, Shigeki; Masuda, Yoshiki; Matsuda, Naoyuki; Matsushima, Asako; Nakada, Taka-Aki; Nakagawa, Satoshi; Nunomiya, Shin; Sadahiro, Tomohito; Shime, Nobuaki; Yatabe, Tomoaki; Hara, Yoshitaka; Hayashida, Kei; Kondo, Yutaka; Sumi, Yuka; Yasuda, Hideto; Aoyama, Kazuyoshi; Azuhata, Takeo; Doi, Kent; Doi, Matsuyuki; Fujimura, Naoyuki; Fuke, Ryota; Fukuda, Tatsuma; Goto, Koji; Hasegawa, Ryuichi; Hashimoto, Satoru; Hatakeyama, Junji; Hayakawa, Mineji; Hifumi, Toru; Higashibeppu, Naoki; Hirai, Katsuki; Hirose, Tomoya; Ide, Kentaro; Kaizuka, Yasuo; Kan'o, Tomomichi; Kawasaki, Tatsuya; Kuroda, Hiromitsu; Matsuda, Akihisa; Matsumoto, Shotaro; Nagae, Masaharu; Onodera, Mutsuo; Ohnuma, Tetsu; Oshima, Kiyohiro; Saito, Nobuyuki; Sakamoto, So; Sakuraya, Masaaki; Sasano, Mikio; Sato, Norio; Sawamura, Atsushi; Shimizu, Kentaro; Shirai, Kunihiro; Takei, Tetsuhiro; Takeuchi, Muneyuki; Takimoto, Kohei; Taniguchi, Takumi; Tatsumi, Hiroomi; Tsuruta, Ryosuke; Yama, Naoya; Yamakawa, Kazuma; Yamashita, Chizuru; Yamashita, Kazuto; Yoshida, Takeshi; Tanaka, Hiroshi; Oda, Shigeto

2018-01-01

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs

Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder.

PubMed

Toyoshima, Kuniyoshi; Fujii, Yutaka; Mitsui, Nobuyuki; Kako, Yuki; Asakura, Satoshi; Martinez-Aran, Anabel; Vieta, Eduard; Kusumi, Ichiro

2017-08-01

In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearman's correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Physical Disabilities Related to the Depressive Mental States of Japanese Patients with Subacute Myelo-optico-neuropathy.

PubMed

Konishi, Tetsuro

2018-05-18

Objective The aim of this study was to clarify the clinical conditions related to the depressive mental states in Japanese patients with subacute myelo-optico-neuropathy (SMON), caused by clioquinol intoxication more than 40 years previously. Materials and methods The changes in the mental states with aging were investigated in 25 Japanese SMON patients (mean age: 77.2 years old, range: 53-90) using a Japanese version of the Zung Self-rating Depression Scale (J-SDS) questionnaires with supportive interviews by the clinical psychotherapist and medical checkup records. These mental and medical examinations were repeated more than twice within 2 to 11 years' interval. The J-SDS questionnaires were also examined in 25 age-matched non-SMON elderly people. Results The total J-SDS scores of most of the SMON patients decreased with age without significant changes in the mean Barthel index scores during this study period. The mean J-SDS scores at the first and latest studies were significantly higher than in the age-matched healthy elderly people. The total J-SDS scores of the latest study were significantly correlated with the degree of physical disability, such as the inverse total Barthel index scores, severity of SMON or gait disturbance, but not with the age. Conclusion The total J-SDS scores of most of the SMON patients tended to decrease with age. Repeating mental supportive interviews and medical examinations by experts helped to improve the depressive mental state and revealed close relationship between the mental state and the physical disabilities of the SMON patients.

Driving clinical study efficiency by using a productivity breakdown model: comparative evaluation of a global clinical study and a similar Japanese study.

PubMed

Takahashi, K; Sengoku, S; Kimura, H

2011-02-01

A fundamental management imperative of pharmaceutical companies is to contain surging costs of developing and launching drugs globally. Clinical studies are a research and development (R&D) cost driver. The objective of this study was to develop a productivity breakdown model, or a key performance indicator (KPI) tree, for an entire clinical study and to use it to compare a global clinical study with a similar Japanese study. We, thereby, hope to identify means of improving study productivity. We developed the new clinical study productivity breakdown model, covering operational aspects and cost factors. Elements for improving clinical study productivity were assessed from a management viewpoint by comparing empirical tracking data from a global clinical study with a Japanese study with similar protocols. The following unique and material differences, beyond simple international difference in cost of living, that could affect the efficiency of future clinical trials were identified: (i) more frequent site visits in the Japanese study, (ii) head counts at the Japanese study sites more than double those of the global study and (iii) a shorter enrollment time window of about a third that of the global study at the Japanese study sites. We identified major differences in the performance of the two studies. These findings demonstrate the potential of the KPI tree for improving clinical study productivity. Trade-offs, such as those between reduction in head count at study sites and expansion of the enrollment time window, must be considered carefully. © 2010 Blackwell Publishing Ltd.

Clinical characteristics of patients with gender identity disorder at a Japanese gender identity disorder clinic.

PubMed

Okabe, Nobuyuki; Sato, Toshiki; Matsumoto, Yosuke; Ido, Yumiko; Terada, Seishi; Kuroda, Shigetoshi

2008-01-15

The aim of this study was to examine the clinical characteristics of patients with gender identity disorder (GID) at a GID clinic in Japan. A total of 603 consecutive patients were evaluated at the GID clinic using clinical information and results of physical and neurological examinations. Using DSM-IV criteria, 579 patients (96.0%) were diagnosed with GID. Four patients were excluded for transvestic fetishism, eight for homosexuality, five for schizophrenia, three for personality disorders, and four for other psychiatric disorders. Among the GID patients, 349 (60.3%) were the female-to-male (FTM) type, and 230 (39.7%) were the male-to-female (MTF) type. Almost all FTM-type GID patients started to feel discomfort with their sex before puberty and were sexually attracted to females. The proportion of FTM patients who had experienced marriage as a female was very low, and very few had children. Therefore, FTM-type GID patients seem to be highly homogeneous. On the other hand, various patterns of age at onset and sexual attraction existed among MTF patients. Among the MTF-type GID patients, 28.3% had married as males and 18.7% had sired children. Thus, MTF-type GID patients seem to be more heterogeneous.

The serum vaspin levels are reduced in Japanese chronic hemodialysis patients.

PubMed

Inoue, Junko; Wada, Jun; Teshigawara, Sanae; Hida, Kazuyuki; Nakatsuka, Atsuko; Takatori, Yuji; Kojo, Shoichirou; Akagi, Shigeru; Nakao, Kazushi; Miyatake, Nobuyuki; McDonald, John F; Makino, Hirofumi

2012-12-03

Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients. Healthy Japanese control volunteers (control; n = 95, 49.9 ± 6.91 years) and Japanese patients undergoing hemodialysis therapy (HD; n = 138, 51.4 ± 10.5 years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system. The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n = 5) and HD patients (n = 11) exhibited much higher levels (> 10 ng/ml; Vaspin High group), while the rest of the population exhibited lower levels (< 3 ng/ml; Vaspin Low group). By comparing the patients in the Vaspin Low group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87 ± 0.24 ng/ml) than in the HD patients (0.32 ± 0.15 ng/ml) (p < 0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects. The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin Low group.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

PubMed

Nishida, Osamu; Ogura, Hiroshi; Egi, Moritoki; Fujishima, Seitaro; Hayashi, Yoshiro; Iba, Toshiaki; Imaizumi, Hitoshi; Inoue, Shigeaki; Kakihana, Yasuyuki; Kotani, Joji; Kushimoto, Shigeki; Masuda, Yoshiki; Matsuda, Naoyuki; Matsushima, Asako; Nakada, Taka-Aki; Nakagawa, Satoshi; Nunomiya, Shin; Sadahiro, Tomohito; Shime, Nobuaki; Yatabe, Tomoaki; Hara, Yoshitaka; Hayashida, Kei; Kondo, Yutaka; Sumi, Yuka; Yasuda, Hideto; Aoyama, Kazuyoshi; Azuhata, Takeo; Doi, Kent; Doi, Matsuyuki; Fujimura, Naoyuki; Fuke, Ryota; Fukuda, Tatsuma; Goto, Koji; Hasegawa, Ryuichi; Hashimoto, Satoru; Hatakeyama, Junji; Hayakawa, Mineji; Hifumi, Toru; Higashibeppu, Naoki; Hirai, Katsuki; Hirose, Tomoya; Ide, Kentaro; Kaizuka, Yasuo; Kan'o, Tomomichi; Kawasaki, Tatsuya; Kuroda, Hiromitsu; Matsuda, Akihisa; Matsumoto, Shotaro; Nagae, Masaharu; Onodera, Mutsuo; Ohnuma, Tetsu; Oshima, Kiyohiro; Saito, Nobuyuki; Sakamoto, So; Sakuraya, Masaaki; Sasano, Mikio; Sato, Norio; Sawamura, Atsushi; Shimizu, Kentaro; Shirai, Kunihiro; Takei, Tetsuhiro; Takeuchi, Muneyuki; Takimoto, Kohei; Taniguchi, Takumi; Tatsumi, Hiroomi; Tsuruta, Ryosuke; Yama, Naoya; Yamakawa, Kazuma; Yamashita, Chizuru; Yamashita, Kazuto; Yoshida, Takeshi; Tanaka, Hiroshi; Oda, Shigeto

2018-01-01

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM , [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.

PubMed

Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro

2017-07-01

Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Proteomic alteration in gastic adenocarcinomas from Japanese patients

PubMed Central

Yoshihara, Takahiro; Kadota, Yoshito; Yoshimura, Yoshiyuki; Tatano, Yutaka; Takeuchi, Naohiro; Okitsu, Hiroshi; Umemoto, Atsushi; Yamauchi, Takashi; Itoh, Kohji

2006-01-01

Background Gastric adenocarcinomas comprise one of the common types of cancers in Asian countries including Japan. Comprehensive protein profiling of paired surgical specimens of primary gastric adenocarcinomas and nontumor mucosae derived from Japanese patients was carried out by means of two-dimensional gel electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as putative clinical biomarkers and molecular targets for chemotherapy. Results Relatively common alterations in protein expression were revealed in the tumor tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG-1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II, glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa stomach-specific protein with putative tumor suppressor activity, were detected. RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression in tumor tissues. Conclusion A possible pathological role for down-regulation of FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific decreases in gene and protein expression of FOV in patients may be utilized as clinical biomarkers for effective diagnosis and assessment of gastric cancer. PMID:17187689

Experience with alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures.

PubMed

Iwamoto, Jun; Uzawa, Mitsuyoshi

2016-01-01

A retrospective study was performed to evaluate the outcome of alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures. Thirty-five Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures (mean age at baseline 58.2 years) who had been treated with alendronate for over 7 years in our outpatient clinic were analyzed. The lumbar spine or total hip bone mineral density (BMD) was measured using dual energy X-ray absorptiometry; the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and the serum levels of alkaline phosphatase (ALP) were monitored; the incidence of fractures during the 7-year treatment period was then assessed. The urinary NTX and serum ALP levels decreased (-46.1% at 3 months and -21.1% at 7 years, respectively) and the lumbar spine and total hip BMD increased (+14.2 and +10.1% at 7 years, respectively), compared with the baseline values. Four patients (11.4%) experienced vertebral fractures, and one patient (2.9%) experienced a nonvertebral fracture. No serious adverse events were observed, including osteonecrosis of the jaw or atypical femoral fractures. These results suggested that alendronate suppressed bone turnover and increased the lumbar spine and total hip BMD from the baseline values over the course of the 7-year treatment period without causing any severe adverse events in Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures.

One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

PubMed

Oshima, Yuji; Kimoto, Kenichi; Yoshida, Noriko; Fujisawa, Kimihiko; Sonoda, Shozo; Kubota, Toshiaki; Murata, Toshinori; Sakamoto, Taiji; Yoshida, Shigeo; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-01-01

To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 μm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients. © 2017 S. Karger AG, Basel.

Clinical presentation and outcome of avoidant/restrictive food intake disorder in a Japanese sample.

PubMed

Nakai, Yoshikatsu; Nin, Kazuko; Noma, Shun'ichi; Hamagaki, Seiji; Takagi, Ryuro; Teramukai, Satoshi; Wonderlich, Stephen A

2017-01-01

We conducted a study of the clinical presentation and outcome in patients with avoidant/restrictive food intake disorder (ARFID), aged 15-40years, and compared this group to an anorexia nervosa (AN) group in a Japanese sample. A retrospective chart review was completed on 245 patients with feeding and eating disorders (FEDs), analyzing prevalence, clinical presentation, psychopathological properties, and outcomes. Using the DSM-5 criteria, 27 (11.0%) out of the 245 patients with a FED met the criteria for ARFID at entry. All patients with ARFID were women. In terms of eating disorder symptoms, all patients with ARFID had restrictive eating related to emotional problems and/or gastrointestinal symptoms. However, none of the ARFID patients reported food avoidance related to sensory characteristics or functional dysphagia. Additionally, none of them exhibited binge eating or purging behaviors, and none of them reported excessive exercise. The ARFID group had a significantly shorter duration of illness, lower rates of admission history, and less severe psychopathology than the AN group. The ARFID group reported significantly better outcome results than the AN group. These results suggest that patients with ARFID in this study were clinically distinct from those with AN and somewhat different from pediatric patients with ARFID in previous studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

PubMed

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

2014-09-01

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

[Clinical effects of Lactobacillus acidophilus strain L-55-contained yogurt on symptoms of Japanese cedar pollen allergy].

PubMed

Kimura, Goro; Akagi, Hirofumi; Okada, Chiharu; Hirano, Atsushi; Amano, Yoshimi; Ohmura, Etsuko; Nakashige, Yoshito; Sunada, Yosuke; Fujii, Yusuke; Nakamura, Syoji; Soda, Ryo; Takahashi, Kiyoshi

2012-05-01

It has been reported that oral administration of Lactobacillus acidophilus strain L-55 (L-55) suppressed nasal symptom and antigen-specific IgE induced by antigen challenge in mice. We investigated clinical effects of L-55-contained yogurt on symptoms and IgE production in the patients with Japanese cedar pollinosis. The study was performed as a randomized double blind placebo-controlled trial. L-55-contained yogurt (L-55 yogurt) or placebo yogurt was started to administer to each subject from 4 weeks prior to the onset of Japanese cedar pollen release for total 13 weeks. The mean value of symptom score and symptom medication score were lower in L-55 yogurt group compared with placebo yogurt group during 5th week to 9th week from the first week of Japanese cedar pollination. Especially, in medicated subjects, total symptom score and throat symptom score were significantly lower in L-55 yogurt group compared with placebo yogurt group at 5th and 4th week from the first week of Japanese cedar pollination, respectively. Moreover, in medicated subjects, change ratio of serum total IgE was significantly lower in L-55 yogurt group compared with placebo yogurt group at 1st week from the first week of Japanese cedar pollination. Intake of L-55 during Japanese cedar pollinating season may be effective in alleviating the allergic symptoms related to Japanese cedar pollinosis. From these finding, it was suggested that L-55 is a possible candidate as a complementary medicine for Japanese cedar pollinosis.

Survival benefit of pancreaticoduodenectomy in a Japanese fashion for a limited group of patients with pancreatic head cancer.

PubMed

Takao, Sonshin; Shinchi, Hiroyuki; Maemura, Kosei; Kurahara, Hiroshi; Natsugoe, Shoji; Aikou, Takashi

2008-01-01

To evaluate the clinical benefit of pancreaticoduodenectomy in a Japanese fashion for patients with pancreatic head cancer. One hundred and one patients underwent pancreatectomy for pancreatic head cancer between 1980 and 2001. Of these, 40 patients in the extended resection (ER) group had an extended lymphadenectomy and neural plexus dissection as a Japanese fashion, while 61 patients in the conventional resection (CR) group. Tumor status, morbidity, mortality, survival and pattern of recurrence were retrospectively studied. The incidence of R0 operations in the ER group was higher than that in the CR group (p<0.01). The actuarial 5-year survival rate (30.6%) of patients with pStage IIA or IIB in the ER group was significantly higher than that (8.2%) in the CR group (p=0.04) because local recurrence (47%) in the CR group was higher than that (25%) in the ER group (p=0.02). In an immunohistochemical study of isolated tumor cells (ITCs), 13 patients (57%) with lymph node ITCs were included in the 23 pN0 patients. Pancreaticoduodenectomy in a Japanese fashion with an adequate extended resection might bring a survival benefit for patients with pStage IIA or IIB pancreatic head cancer.

Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese men.

PubMed

Tsuboi, Ryoji; Arano, Osamu; Nishikawa, Tooru; Yamada, Hidekazu; Katsuoka, Kensei

2009-08-01

Minoxidil is efficacious in inducing hair growth in patients with androgenetic alopecia by inducing hair follicles to undergo transition from the early to late anagen phase. Although the efficacy of 1% topical minoxidil has been confirmed in Japan, no controlled study of 5% topical minoxidil has been conducted using male Japanese subjects. The objective of this trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil in a double-blind controlled study with male, Japanese androgenetic alopecia patients as the subjects. The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia who were administered either 5% topical minoxidil (n = 150) or 1% topical minoxidil (n = 150) for 24 weeks. The mean change from the baseline in non-vellus hair/cm(2), the primary efficacy variable, was 26.4 (n = 142) in the 5% topical minoxidil group and 21.2 (n = 144) in the 1% topical minoxidil group at 16 weeks, the main time point for the evaluation. The difference between the groups was significant (P = 0.020). The incidence of adverse events was 8.7% (13/150) in the 5% group and 5.3% (8/150) in the 1% group, with no significant difference between the groups (chi(2)-test: P = 0.258). Our findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia.

Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro

2016-10-01

To evaluate the efficacy and safety of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes. We conducted interim analyses at 3 months of a 3-year prospective study of patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015, and whose data were locked by 16 January 2016. Changes in glycemic control, blood pressure, and laboratory variables from baseline, and incidence of adverse drug reactions (ADRs). Of 11,412 patients initially registered, efficacy and safety data were available for 3481 (30.5%) and 4360 (38.2%) patients, respectively. Hemoglobin A1c and fasting plasma glucose decreased by 0.67% and 28.8 mg/dL, respectively, at 3 months/last assessment (both P < .001) from baseline (8.00% and 166.4 mg/dL, respectively). Blood pressure and lipid levels also improved significantly. There were 258 ADRs in 194 patients. The ADRs included 'renal and urinary disorders' (system organ class) in 110 patients (2.5%). These 3-month interim results indicate that ipragliflozin improved glycemic control, lipids, and blood pressure with low rates of ADRs in Japanese patients with type 2 diabetes in real-world clinical practice. The results were consistent with those of placebo-controlled, randomized clinical trials. Clinicaltrials.gov identifier: NCT02479399.

The prognostic impact of worsening renal function in Japanese patients undergoing percutaneous coronary intervention with acute coronary syndrome.

PubMed

Murata, Nobuhiro; Kaneko, Hidehiro; Yajima, Junji; Oikawa, Yuji; Oshima, Toru; Tanaka, Shingo; Kano, Hiroto; Matsuno, Shunsuke; Suzuki, Shinya; Kato, Yuko; Otsuka, Takayuki; Uejima, Tokuhisa; Nagashima, Kazuyuki; Kirigaya, Hajime; Sagara, Koichi; Sawada, Hitoshi; Aizawa, Tadanori; Yamashita, Takeshi

2015-10-01

The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear. With a single hospital-based cohort in the Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge. WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI. In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier

Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.

PubMed

Sugiyama, Ikuo; Bouillon, Thomas; Yamaguchi, Masayuki; Suzuki, Hikoe; Hirota, Takashi; Fink, Martin

2015-04-01

Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Prehospital delay and independent/interdependent construal of self among Japanese patients with acute myocardial infarction.

PubMed

Fukuoka, Yoshimi; Dracup, Kathleen; Rankin, Sally H; Froelicher, Erika Sivarajan; Kobayashi, Fumio; Hirayama, Haro; Ohno, Miyoshi; Matsumoto, David

2005-05-01

Reducing the time from symptom onset to reperfusion therapy is an important approach to minimizing myocardial damage and to preventing death from acute myocardial infarction (AMI). Previous studies suggest that certain ethnic or national groups, such as the Japanese, are more likely to delay in accessing care than other groups. The aims of this paper were the following; (1) to examine whether culture (defined as independent and interdependent construal of self) is associated with delay in accessing medical care in Japanese patients experiencing symptoms of AMI; (2) to determine if the relationship between independent and interdependent construal of self and prehospital delay time is mediated by cognitive responses and/or emotional responses; and (3) to determine if independent and interdependent construal of self independently predicts choice of treatment site (clinic vs. hospital). A cross-sectional study was conducted at hospitals in urban areas in Japan. One hundred and forty-five consecutive patients who were admitted with AMI within 72 h of the onset of symptoms were interviewed using the modified response to symptoms questionnaire and the independent and interdependent construal of self scale. The interdependent construal of self scores were significantly associated with prehospital delay time, controlling for demographics, medical history, and symptoms (p<.001). However, the relationship between independent and interdependent self and prehospital delay times was not mediated by cognitive or emotional responses. In multiple logistic regression analysis, patients with high independent construal of self were more likely to seek care at a hospital rather than a clinic compared to those with lower independent construal of self. In conclusion, cultural variation within this Japanese group was observed and was associated with prehospital delay time.

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.

PubMed

Nishikawa, Masakatsu; Isshiki, Takaaki; Kimura, Takeshi; Ogawa, Hisao; Yokoi, Hiroyoshi; Miyazaki, Shunichi; Ikeda, Yasuo; Nakamura, Masato; Tanaka, Yuko; Saito, Shigeru

2017-04-01

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

Long-term safety and efficacy of canakinumab in cryopyrin-associated periodic syndrome: results from an open-label, phase III pivotal study in Japanese patients.

PubMed

Yokota, Shumpei; Imagawa, Tomoyuki; Nishikomori, Ryuta; Takada, Hidetoshi; Abrams, Ken; Lheritier, Karine; Heike, Toshio; Hara, Toshiro

2017-01-01

To assess the long-term safety and efficacy of canakinumab in Japanese patients with cryopyrin-associated periodic syndrome (CAPS). In this open-label phase 3 study, Japanese patients aged ≥2 years with CAPS received canakinumab 2-8 mg/kg subcutaneously every 8 weeks. The duration of the core treatment phase was 24 weeks followed by 22 months extension phase. The primary objective was the proportion of patients free of clinical and serologic relapse at week 24. The study enrolled 19 Japanese patients (median age, 14 years; range, 2-48 years) with CAPS [MWS, 7 (36.8%); NOMID, 12 (63.2%)] for a median of 109 weeks. Fifteen patients (79%) achieved a complete response by day 15, 18 (94.7%) by week 24 and all by week 48. At the end of the study, 18 (95%) were free from relapse and 11 (57.9%) were assessed as having no disease activity by the PGA. Thirteen (68%) patients (MWS, 4; NOMID, 9) had their canakinumab dose increased during the trial. All patients experienced at least one adverse event (AE), the most common being infections (100%) and 5 (26.3%) reported serious AEs. No deaths were reported and the only patient who discontinued the study early withdrew consent. Regular canakinumab treatment every 8 weeks at dose levels from 2-8 mg/kg, based on the clinical need, represents a successful strategy to induce rapid and complete response while maintain long-term disease control in Japanese patients with CAPS. The safety profile of canakinumab was consistent with that observed from previous studies.

Development and evaluation of a self-efficacy instrument for Japanese sleep apnea patients receiving continuous positive airway pressure treatment

PubMed Central

Saito, Ayako; Kojima, Shigeko; Sasaki, Fumihiko; Hayashi, Masamichi; Mieno, Yuki; Sakakibara, Hiroki; Hashimoto, Shuji

2015-01-01

The purpose of this study was to develop and evaluate a self-efficacy instrument for Japanese obstructive sleep apnea (OSA) patients treated with continuous positive airway pressure (CPAP). Analyzed subjects were 653 Japanese OSA patients (619 males and 34 females) treated with CPAP at a sleep laboratory in a respiratory clinic in a Japanese city. Based on Bandura’s social cognitive theory, the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese (CSESA-J) was developed by a focus group of experts, using a group interview of OSA patients for the items of two previous self-efficacy scales for Western sleep apnea patients receiving CPAP treatment. CSESA-J has two subscales, one for self-efficacy and the other for outcome expectancy, and consists of a total of 15 items. Content validity was confirmed by the focus group. Confirmatory factor analysis showed that the factor loadings of self-efficacy and outcome expectancy were 0.47–0.76 and 0.41–0.92, respectively, for the corresponding items. CSESA-J had a significant but weak positive association with the General Self-Efficacy Scale, and a strong positive association with “Self-efficacy scale on health behavior in patients with chronic disease.” Cronbach’s alpha coefficient was 0.85 for the self-efficacy subscale and 0.89 for the outcome expectancy subscale. The intraclass correlation coefficient using data from the first and second measurements with CSESA-J for a subset of 130 subjects was 0.93 for the self-efficacy and outcome expectancy subscales. These results support CSESA-J as a reliable and valid instrument for measuring the self-efficacy of Japanese OSA patients treated with CPAP. Further studies are warranted to confirm validity for female OSA patients and generalizability. PMID:25678832

Clinical characteristics of patients with tinnitus evaluated with the Tinnitus Sample Case History Questionnaire in Japan: A case series

PubMed Central

Kojima, Takashi; Kanzaki, Sho; Oishi, Naoki; Ogawa, Kaoru

2017-01-01

Background The Tinnitus Sample Case History Questionnaire was determined as a standardized questionnaire for obtaining patient case histories and for characterizing patients into subgroups at the Tinnitus Research Initiative in 2006. In this study, we developed a Japanese version of this questionnaire for evaluating the clinical characteristics of patients with tinnitus. The Japanese version of the questionnaire will be available for evaluating treatments for tinnitus and for comparing data on tinnitus in research centers. Aims/Objectives To evaluate the clinical characteristics of patients with tinnitus in Japan using a newly developed Japanese version of Tinnitus Sample Case History Questionnaire. Study design This was a prospective study based on patient records. Setting University hospitals, general hospitals, and clinics. Subjects and methods We collected patient data using a Japanese translated version of the Tinnitus Sample Case History Questionnaire. In total, 584 patients who visited our institutions in Japan between August 2012 and March 2014 were included (280 males and 304 females; age 13–92 years; mean age, 60.8). We examined patients after dividing them into two groups according to the presence or absence of hyperacusis. The collected results were compared with those from the Tinnitus Research Initiative database. Results Compared with the TRI database, there were significantly more elderly female patients and fewer patients with trauma-associated tinnitus. There was a statistically lower ratio of patients with hyperacusis. We found that patients with tinnitus in addition to hyperacusis had greater tinnitus severity and exhibited higher rates of various complications. Conclusion The Japanese version of the Tinnitus Sample Case History Questionnaire developed in this study can be a useful tool for evaluating patients with tinnitus in Japan. The results of this multicenter study reflect the characteristics of patients with tinnitus who require medical

Clinical characteristics of patients with tinnitus evaluated with the Tinnitus Sample Case History Questionnaire in Japan: A case series.

PubMed

Kojima, Takashi; Kanzaki, Sho; Oishi, Naoki; Ogawa, Kaoru

2017-01-01

The Tinnitus Sample Case History Questionnaire was determined as a standardized questionnaire for obtaining patient case histories and for characterizing patients into subgroups at the Tinnitus Research Initiative in 2006. In this study, we developed a Japanese version of this questionnaire for evaluating the clinical characteristics of patients with tinnitus. The Japanese version of the questionnaire will be available for evaluating treatments for tinnitus and for comparing data on tinnitus in research centers. To evaluate the clinical characteristics of patients with tinnitus in Japan using a newly developed Japanese version of Tinnitus Sample Case History Questionnaire. This was a prospective study based on patient records. University hospitals, general hospitals, and clinics. We collected patient data using a Japanese translated version of the Tinnitus Sample Case History Questionnaire. In total, 584 patients who visited our institutions in Japan between August 2012 and March 2014 were included (280 males and 304 females; age 13-92 years; mean age, 60.8). We examined patients after dividing them into two groups according to the presence or absence of hyperacusis. The collected results were compared with those from the Tinnitus Research Initiative database. Compared with the TRI database, there were significantly more elderly female patients and fewer patients with trauma-associated tinnitus. There was a statistically lower ratio of patients with hyperacusis. We found that patients with tinnitus in addition to hyperacusis had greater tinnitus severity and exhibited higher rates of various complications. The Japanese version of the Tinnitus Sample Case History Questionnaire developed in this study can be a useful tool for evaluating patients with tinnitus in Japan. The results of this multicenter study reflect the characteristics of patients with tinnitus who require medical care in Japan. Our data provides a preliminary basis for an international comparison of

Safety and benefits of a tablet combining losartan and hydrochlorothiazide in Japanese diabetic patients with hypertension.

PubMed

Kinouchi, Kenichiro; Ichihara, Atsuhiro; Sakoda, Mariyo; Kurauchi-Mito, Asako; Itoh, Hiroshi

2009-12-01

This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

Clinical validity of the Japanese version of WAIS-III short forms: Adaptation for patients with mild neurocognitive disorder and dementia.

PubMed

Takeda, Mihoko; Nakaya, Makoto; Kikuchi, Yoko; Inoue, Sayaka; Kamata, Tomoyuki

2018-01-01

We investigated the Japanese WAIS-III short form utility in mild neurocognitive disorder and dementia. Our sample consisted of 108 old patients (ages: 65-89; mean age = 78.3). Fifteen short forms (SFs) and full-scale (FS) IQs were compared. The SFs included Dyads (SF1, SF2), Triads (SF3), Tetrads (SF4, SF5, SF6, SF7), Pentad (SF8), Six-subtest (SF9), Seven-subtests (SF10(a)(b), SF11(a)(b), SF12), and Nine-subtest (SF13). Correlations between SFIQs and FSIQ were all significant. Significant differences also were found in paired t-test between FSIQ and 5 SFIQs (SF2: t = -4.16, SF5: t = -7.06, SF7; t = 2.59, SF10(a): t = 2.56, SF12: t = -4.82; p < .05). On the point of clinical accuracy, two SFs led to an appropriate estimated IQ (SF11(a): 84.3%, SF13: 91.7%; within 95% confidence interval and 2 standard error of measurements of FSIQ). However, SF13 was considered to still have a long administration time. The present results suggest that SF11(a) could be the most useful to estimate IQ for Japanese speaking patients with mild neurocognitive disorder and dementia. SF11(a) consists of seven subtests of Similarities, Arithmetic, Digit Span, Information, Picture Completion, Digit Symbol-Coding, and Matrix Reasoning (Ryan & Ward, 1999), and the formula (Axelrod et al., 2001) should be adopted to convert scaled scores into estimated IQ scores. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of bezlotoxumab for prevention of recurrent Clostridium difficile infection (CDI) in Japanese patients.

PubMed

Mikamo, Hiroshige; Aoyama, Norihiro; Sawata, Miyuki; Fujimoto, Go; Dorr, Mary Beth; Yoshinari, Tomoko

2018-02-01

Recurrent Clostridium difficile infection is considered as a significant health care burden. The global study (MODIFY II) of antibody treatment (bezlotoxumab) for the prevention of recurrent C. difficile infection includes Japanese patients (95 subjects); The aim of this subgroup analysis is to report the data obtained from Japanese patients. Patients with C. difficile infection receiving standard of care antibiotic treatment and a single infusion of bezlotoxumab 10 mg/kg, actoxumab 10 mg/kg + bezlotoxumab 10 mg/kg or placebo. Recurrent C. difficile infection through Week 12 was evaluated. In the Full Analysis Set (93 subjects), 91% were older than 65 years of age and 93% were hospitalized at the time of study entry. The standard of care antibiotic for C. difficile infection was metronidazole for 57 subjects and vancomycin for 36 subjects. The recurrent C. difficile infection rate was 46% in the placebo, 21% in the bezlotoxumab (p = 0.0197) and 28% in the actoxumab + bezlotoxumab group. No additive recurrent C. difficile infection-reducing effect with the addition of actoxumab was demonstrated. There were no events representing safety concern in bezlotoxumab. Among 54 clinical isolates of C. difficile as a baseline culture in Japanese patients, the common ribotypes were 052 (28%), 018 (19%), 002 (15%) and 369 (9%). It showed distinctly different distribution from that in the United States and Europe. The superior effect of bezlotoxumab 10 mg/kg in the prevention of recurrent C. difficile infection suggests that the agent will be useful in the rapidly aging Japanese society. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dysregulated Plasma Glucagon Levels in Japanese Young-adult Type 1 Diabetes Patients.

PubMed

Kawamori, Dan; Katakami, Naoto; Takahara, Mitsuyoshi; Miyashita, Kazuyuki; Sakamoto, Fumie; Yasuda, Tetsuyuki; Matsuoka, Taka-Aki; Shimomura, Iichiro

2018-05-16

Currently, the clinical dynamics of glucagon needs to be revised based on previous data obtained from conventional glucagon radioimmunoassays. In this study, we evaluated plasma glucagon levels in type 1 diabetes patients using a newly-developed sandwich enzyme-linked immunosorbent assay (ELISA), and its association with clinical parameters and markers of diabetes complications were statistically assessed. The plasma glucagon level in 77 Japanese type 1 diabetes patients was 28.1±17.7 pg/mL, and comparable to that reported previously for type 2 diabetes patients. However, the values were widely spread and did not correlate with plasma glucose values. Additionally, the average glucagon levels in patients in a hypoglycemic state (glucose level <80 mg/dL) did not increase (21.7±12.2 pg/mL). The average glucagon level of patients experiencing hypoglycemia unawareness was significantly lower. Plasma glucagon levels evaluated using the new ELISA were dysregulated in type 1 diabetes patients in respect of plasma glucose levels, suggesting dysregulation of secretion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil.

PubMed

Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M; Bonin, Camila Mareti; Vicente, Ana C P; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

2017-01-01

The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil

PubMed Central

Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M.; Bonin, Camila Mareti; Vicente, Ana C. P.; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

2017-01-01

The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic

Study design of J-ELD AF: A multicenter prospective cohort study to investigate the efficacy and safety of apixaban in Japanese elderly patients.

PubMed

Akao, Masaharu; Yamashita, Takeshi; Okumura, Ken

2016-12-01

Apixaban, one of the non-vitamin K antagonist oral anticoagulants, was reported to be effective and safe in stroke prevention in patients with atrial fibrillation (AF) based on the global randomized clinical trial, but data are limited on the efficacy and safety of apixaban in Japanese elderly patients. The J-ELD AF Registry is a large-scale, contemporary observational study, continuously and prospectively registering elderly Japanese patients with AF aged 75 years or older who are currently taking apixaban or the elderly who are to receive apixaban in daily clinical practice, and accumulating the outcomes during one-year follow-up period. In addition to standard baseline characteristics, prothrombin time and anti-Xa activity will be measured to investigate the biomarker characteristics. The primary efficacy endpoints will be stroke and systemic embolism, and the primary safety endpoint will be major bleeding requiring hospitalization. The secondary endpoints in this study will be all-cause death, cardiovascular death, acute myocardial infarction, and the composite of stroke/systemic embolism, cardiovascular death, and acute myocardial infarction. As a primary analysis, the primary/secondary endpoints in the enrolled patients will be totalized for the entire group, and the incidence of events will be described by age, CHADS 2 score, HAS-BLED score, and apixaban dose (5 or 2.5mg bid). The factors that independently predict the incidence of the primary/secondary endpoints will be searched for by Cox regression. The relationship between the biomarkers and the primary/secondary endpoints will also be examined in an explorative manner. This study will provide important information on the efficacy and safety of apixaban in elderly Japanese patients aged 75 years or older, and those of low-dose administration of apixaban (2.5mg bid) for which many of the Japanese elderly are indicated. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights

The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

PubMed

Tominaga, T; Miyazaki, S; Oniyama, Y; Weber, A D; Kondo, T

2017-08-01

The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.

PubMed

Tamaki, Kentaro; Ishida, Takanori; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kanou; Miyashita, Minoru; Amari, Masakazu; Tadano-Sato, Akiko; Takahashi, Yayoi; Watanabe, Mika; McNamara, Keely; Ohuchi, Noriaki; Sasano, Hironobu

2014-05-01

It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion. We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index. There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105). A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.

New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome.

PubMed

Kuniyoshi, Kazuki; Hayashi, Takaaki; Sakuramoto, Hiroyuki; Mishima, Hiroshi; Tsuneoka, Hiroshi; Tsunoda, Kazushige; Iwata, Takeshi; Shimomura, Yoshikazu

2016-11-01

The enhanced S-cone syndrome (ESCS) is a rare hereditary retinal degeneration that has enhanced short wavelength-sensitive cone (S-cone) functions. The longitudinal clinical course of this disease has been rarely reported, and the genetic aspects of ESCS have not been well investigated in the Japanese population. In this report, we present our clinical and genetic findings for 2 patients with ESCS. The patients were 2 unrelated Japanese men. Standard ophthalmic examinations and mutation screening for the NR2E3 gene were performed. Patient 1 was a 36-year-old man, and his clinical findings were typical of ESCS. His decimal best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS after removal of cataracts. Genetic investigations revealed a homozygous truncation frameshift, the p.I307LfsX33 mutation. Patient 2 was an 11-year-old boy when he was first examined by us. His clinical findings were typical of ESCS except for uveitis in the left eye. His decimal BCVA at the age of 39 years was maintained at 1.5 in each eye, although the retinal degeneration and visual field impairments had progressed during the follow-up period. The genetic investigations revealed homozygous mutations of p.R104Q in the NR2E3 gene. The frameshift mutation, p.I307LfsX33, in the NR2E3 gene is a new causative mutation for ESCS. The clinical observations for patient 2 are the longest ever reported. The retinal degeneration caused by this mutation is slowly progressive, and these patients maintained good vision with maintenance of the foveal structure until their late thirties.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

PubMed

Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

2018-02-15

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

A potential protective effect in multilingual patients with semantic dementia: two case reports of patients speaking Taiwanese and Japanese.

PubMed

Liu, Yi-Chien; Yip, Ping-Keung; Fan, Yu-Ming; Meguro, Kenichi

2012-03-01

Several reports have suggested that multilingualism has a protective effect against semantic dementia. Here, we provide further evidence for this effect. The patient was a 75-year-old right-handed Taiwanese woman who had retired after working as a tailor. She was able to speak Taiwanese, Japanese and Mandarin Chinese fluently until 5 years ago. She gradually developed symptoms of profound anomia and difficulty with word-finding. Her mother tongue was Taiwanese and she had learned Japanese as her first symbolized language. She had used Mandarin Chinese for most of her life, but depended on Japanese to read and write (such as reading a newspaper and keeping accounts). However, she could now speak only very simple Taiwanese and Japanese, and could recognize only simple Japanese characters. SECOND: The patient was a 62-year-old right-handed man who had worked as an ironworker. He could speak Taiwanese and Mandarin Chinese fluently until 5 years ago. His mother tongue was Taiwanese. After 5 years of language deterioration, he was unable to communicate with his family members or recognize any characters, including numbers. SPECT RESULTS: Brain perfusion ECD SPECT (Tc-99m-ethyl cysteinate dimer single-photon emission computed tomography) showed less perfusion in the multilingual patient (Case #1) than in the bilingual patient (Case #2). Neuropsychological tests also demonstrated a slower rate of degeneration in the multilingual patient. We speculate that reading and writing in Japanese had a greater impact on the semantic system in Case #1. Thus, this patient showed relatively less degeneration or functional inactivity, as shown by perfusion in the frontal lobe, and this might be due to the persistent activation involved in multilingualism.

Effects of ward rotation on subsequent transition processes of Japanese clinical nurses.

PubMed

Fujino, Mitsuku; Nojima, Yoshiko

2005-03-01

The purpose of this study was to examine the experience of Japanese clinical nurses undertaking a ward rotation in a general hospital, and its effects on subsequent processes relating to: (i) perception of ward rotation; (ii) reactions to the ward transition process; and (iii) outcomes of ward rotation. In-depth interviews were conducted with 21 Japanese clinical nurses who had an average of 8.8 years (SD = 5.50) clinical experience. Findings indicated that participants experienced role overload, role incongruity and/or role underload, role overqualification, or role ambiguity in the new environment. These role stresses created critical emotional distress during the transition process. The high desire for career development facilitated the transition process, while lack of preparation inhibited the transition process. To facilitate smooth transition, well-prepared and structured supports based on reliable interpersonal relationships are necessary. The findings offer significant cues for effective ward rotation programs. The implication for nursing administrators is that appropriate ward rotations enhance confidence and promote effective role development in the new clinical setting.

Characteristics of Japanese Patients with Becker Muscular Dystrophy and Intermediate Muscular Dystrophy in a Japanese National Registry of Muscular Dystrophy (Remudy): Heterogeneity and Clinical Variation.

PubMed

Mori-Yoshimura, Madoka; Mitsuhashi, Satomi; Nakamura, Harumasa; Komaki, Hirofumi; Goto, Kanako; Yonemoto, Naohiro; Takeuchi, Fumi; Hayashi, Yukiko K; Murata, Miho; Takahashi, Yuji; Nishino, Ichizo; Takeda, Shin'ichi; Kimura, En

2018-01-01

Obtaining an adequate number of patients to conduct a natural history study for rare diseases such as Becker muscular dystrophy (BMD) is difficult. The present study used data from Remudy, a national registry for neuromuscular diseases in Japan, to conduct a phenotypic analysis of BMD. We analyzed Remudy data of participants with dystrophinopathy. All participants who were aged 17 and older and were ambulant at age 13 were included in this study. Participants were divided into two groups: those with BMD who were ambulant at age 17, and those with intermediate muscular dystrophy (IMD) who lost ambulation by age 17. Frequent mutations were analyzed by age at ambulation, cardiopulmonary function, and genotype. For clinical comparisons, participants who were administered steroids were excluded. From July 2009 through September 2015, 192 participants had registered with Remudy. Mean participant age was 34.80±13.3 (range, 17-78) years, and 52.1% of participants were ambulant. Of the entire study population, 50.5% had cardiomyopathy and 35.9% had respiratory failure. Three participants required invasive ventilation and 30 required non-invasive ventilation. Nineteen of the 30 non-invasive ventilator users were part-time users. In total, 138 (71.9%) had BMD and 54 (28.1%) had IMD. The most frequent mutation was ex45_ex47del (36 participants). Among participants with frequent in-frame mutations, those with the ex45-49del mutation lost their ambulation earlier than those with the ex45_ex47del mutation. A total of 67 different exon deletions and duplications were identified in the study population. We clarified the clinical phenotypes of Japanese patients with BMD/IMD using data from Remudy. Our results suggest that not only IMD but also BMD are associated with risk of respiratory dysfunction.

Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14

NASA Astrophysics Data System (ADS)

Borjali, Davood

Title: Comparation of clinical and paraclinical findings among patient with Kawasaki disease in Bandar abbas Koodakan Hospital in 2011-14 Kawasaki disease(KD) is a kind of vasculitis diagnosed by clinical manifestation and it caused acquired heart disease in children because of coronary arteries involvement. Method: patient divided to three group of American Japanese and incomplete and also study in two group according to fever days and then clinical features and laboratory data were checked. Result: A total of 150 patients were enrolled during the study period. number of patients with incomplete Kawasaki disease was 128 american group was 28 and Japanese was 4 patients, the most prevalent symptom was scaling of extremities(61 bladder most seen in group with fever more than five days. Keyword: Kawasaki , epidemiology , criteria

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Japanese cancer patient participation in and satisfaction with treatment-related decision-making: A qualitative study.

PubMed

Watanabe, Yoshiko; Takahashi, Miyako; Kai, Ichiro

2008-02-27

Over the last decade, patient involvement in treatment-related decision-making has been widely advocated in Japan, where patient-physician encounters are still under the influence of the long-standing tradition of paternalism. Despite this profound change in clinical practice, studies investigating the actual preferences of Japanese people regarding involvement in treatment-related decision-making are limited. The main objectives of this study were to (1) reveal the actual level of involvement of Japanese cancer patients in the treatment-related decision-making and their overall satisfaction with the decision-making process, and (2) consider the practical implications of increased satisfaction in cancer patients with regard to the decision-making process. We conducted semi-structured interviews with 24 Japanese cancer patients who were recruited from a cancer self-help group in Tokyo. The interviews were qualitatively analysed using the approach described by Lofland and Lofland. The analyses of the patients' interviews focused on 2 aspects: (1) who made treatment-related decisions (the physician or the patient), and (2) the informants' overall satisfaction with the decision-making process. The analyses revealed the following 5 categories of decision-making: 'patient as the active decision maker', 'doctor selection', 'wilfully entrusting the physician', 'compelled decision-making', and 'surrendering decision-making'. While the informants under the first 3 categories were fairly satisfied with the decision-making process, those under the latter 2 were extremely dissatisfied. Informants' views regarding their preferred role in the decision-making process varied substantially from complete physician control to complete patient control; the key factor for their satisfaction was the relation between their preferred involvement in decision-making and their actual level of involvement, irrespective of who the decision maker was. In order to increase patient satisfaction

Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study.

PubMed

Eto, Y; Ohashi, T; Utsunomiya, Y; Fujiwara, M; Mizuno, A; Inui, K; Sakai, N; Kitagawa, T; Suzuki, Y; Mochizuki, S; Kawakami, M; Hosoya, T; Owada, M; Sakuraba, H; Saito, H

2005-01-01

Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.

Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.

PubMed

Sada, Ken-ei; Yamamura, Masahiro; Harigai, Masayoshi; Fujii, Takao; Dobashi, Hiroaki; Takasaki, Yoshinari; Ito, Satoshi; Yamada, Hidehiro; Wada, Takashi; Hirahashi, Junichi; Arimura, Yoshihiro; Makino, Hirofumi

2014-04-23

We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study. In total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated. Using the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n = 61) had significantly lower BVAS (P = 0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n = 95). MPO

Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.

PubMed

Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

2016-07-01

To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

PubMed

Foley, James E; Bhosekar, Vaishali; Kawamori, Ryuzo

2016-01-01

Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM) may respond more favorably to a DPP-4 (dipeptidyl peptidase-4) inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid]) between Japanese and Caucasian populations. This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338) who had been treated in Japan and Caucasian patients (n=1,275) who were treated elsewhere. Change from baseline (Δ) in glycated hemoglobin (HbA1c) at 12 weeks (in millimoles per mole) versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole) for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society) and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program), while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r (2)=0.36; and 0.41, r (2)=0.15), and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol/mol (0.2% NGSP HbA1c) at any given baseline HbA1c than in Caucasians (P=0.01). The present pooled analysis suggests that Japanese patients respond better to vildagliptin treatment compared with Caucasians. However, when glycemic control was corrected by using the same glycemic standard, the difference in HbA1c

Time-Dependent Changes in Psychosocial Distress in Japanese Patients with Implantable Cardioverter Defibrillators.

PubMed

Saito, Nao; Taru, Chiemi; Miyawaki, Ikuko

2016-12-02

This prospective study clarified changes in the mood states of Japanese patients with implantable cardioverter defibrillators as well as factors related to the mood states. Using a longitudinal repeated-measure design, 29 patients with implantable cardioverter defibrillators completed the Profile of Mood States-Short Form Japanese Version questionnaire before discharge and 1, 4, 7, and 13 months after implantation. One month after discharge, the mood states of the patients with implantable cardioverter defibrillators improved. From 7 to 13 months after discharge, moods deteriorated; 13 months after discharge, moods were equivalent to those at the time of discharge. No relationship with defibrillation experience was detected in this study, but employment, age, sex, and lack of experience of syncopal attack were factors related to poor mood states for patients with implantable cardioverter defibrillators. Therefore, Japanese patients with implantable cardioverter defibrillators with any factor deteriorating their mood state should be monitored so that their mood state does not deteriorate again between six months and one year after implantation.

Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study.

PubMed

Hosoya, Tatsuo; Sasaki, Tomomitsu; Ohashi, Tetsuo

2017-03-01

Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose-response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose-response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be -44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose-response relationship in Japanese hyperuricemic patients with or without gout.

Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients: The CA-ATTEND study.

PubMed

Aoki, Shiro; Hosomi, Naohisa; Nezu, Tomohisa; Teshima, Tsukasa; Sugii, Hitoshi; Nagahama, Shinobu; Kurose, Yoshiki; Maruyama, Hirofumi; Matsumoto, Masayasu

2017-01-01

Blood pressure control is important in post-stroke hypertensive patients and antihypertensive treatment is recommended for such patients. Ca-channel blockers are recommended as the medications of choice for the treatment of post-stroke patients. Here, we report the results of a large-scale prospective post-marketing surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%, 69.0 ± 10.9 years) treated with cilnidipine, with regard to blood pressure control and adverse reactions. Cilnidipine treatment caused a decrease in both clinic and home blood pressures 2 months after the beginning of treatment, and the decreased blood pressure was maintained until the end of 12 months' observation. The proportion of patients in whom clinic blood pressure was well controlled (<140/90 mmHg) increased from 21.5% to 65.3% in cilnidipine treatment, with no differences in effectiveness among the various clinical subtypes of stroke. In total, 346 adverse events occurred, with an overall incidence of 8.9% (238 of 2667 patients). In the elderly group, specifically, a fall and a hip fracture each occurred in 1 (0.1%) patient. These results indicate that cilnidipine was effective in treating uncontrolled blood pressure and was well tolerated in Japanese post-stroke hypertensive patients in a real-world clinical setting.

Japanese Clinical Practice Guideline for Head and Neck Cancer.

PubMed

Nibu, Ken-Ichi; Hayashi, Ryuichi; Asakage, Takahiro; Ojiri, Hiroya; Kimata, Yoshihiro; Kodaira, Takeshi; Nagao, Toshitaka; Nakashima, Torahiko; Fujii, Takashi; Fujii, Hirofumi; Homma, Akihiro; Matsuura, Kazuto; Monden, Nobuya; Beppu, Takeshi; Hanai, Nobuhiro; Kirita, Tadaaki; Kamei, Yuzuru; Otsuki, Naoki; Kiyota, Naomi; Zenda, Sadamoto; Omura, Ken; Omori, Koichi; Akimoto, Tetsuo; Kawabata, Kazuyoshi; Kishimoto, Seiji; Kitano, Hiroya; Tohnai, Iwai; Nakatsuka, Takashi

2017-08-01

The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members. Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function. In this article, we described

Chromobacterium violaceum nosocomial pneumonia in two Japanese patients at an intensive care unit.

PubMed

Hagiya, Hideharu; Murase, Tomoko; Suzuki, Masato; Shibayama, Keigo; Kokumai, Yumi; Watanabe, Naoto; Maki, Miyako; Otsuka, Fumio

2014-02-01

Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C. violaceum infection is likely to change. We report two cases of C. violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C. violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C. violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C. violaceum, can contribute to C. violaceum infection in a hospital environment. Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Disease. Published by Elsevier Ltd. All rights reserved.

Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

PubMed Central

Koga, Michiaki; Kanda, Takashi; Murata, Kenya; Suzuki, Takashi; Kurono, Hiroko; Kunimoto, Masanari; Kaida, Ken-ichi; Mukaino, Akihiro; Sakai, Waka; Maeda, Yasuhiro; Matsuo, Hidenori

2015-01-01

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG. PMID:25790156

Costs associated with febrile neutropenia in Japanese patients with primary breast cancer: post-hoc analysis of a randomized clinical trial.

PubMed

Miyake, Osamu; Murata, Kyoko; Tanaka, Shiro; Ishiguro, Hiroshi; Toi, Masakazu; Tamura, Kazuo; Kawakami, Koji

2018-05-01

Febrile neutropenia (FN), a decrease in blood neutrophils accompanied by fever, is a major adverse event (AE) associated with cancer chemotherapy. We aimed to estimate the direct medical costs associated with FN management in breast cancer patients within a clinical trial with pegfilgrastim, a pegylated form of recombinant granulocyte colony-stimulating factor (G-CSF). We obtained data from 346 Japanese breast cancer patients in a randomized, placebo-controlled clinical trial comparing FN incidence due to TC adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) between pegfilgrastim-treated and placebo groups. We estimated mean costs for chemotherapy drugs, drugs for all AEs and FN, and hospitalization for all AEs and FN. We also calculated mean costs associated with drugs and hospitalization for FN specifically for patients who developed FN in the placebo group. For the pegfilgrastim and placebo groups, the total cost during the first cycle of chemotherapy was ¥189 135 and ¥98 106. This difference is associated with prophylactic use of pegfilgrastim. Our analysis clarified in the placebo group that FN incidents of 119/173 (68.6%), the mean drug cost related to all AEs and hospitalization caused by the first cycle of chemotherapy were ¥14 411and ¥11 180, respectively. The cost of each for FN treatment was ¥16 429 for the placebo group. The mean treatment cost for patients who developed FN in placebo group, was ¥11 145 for drugs and ¥28 420 for drugs and hospitalization. Pegfilgrastim reduced the costs incurred for both drugs and hospitalization for AEs as well as FN, although the total medical cost during the chemotherapy increased. Our study constitutes baseline data for further health economic evaluations of pegfilgrastim.

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer.

PubMed

Shitara, Kohei; Muro, Kei; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Komatsu, Yoshito; Nishina, Tomohiro; Yamaguchi, Kensei; Segawa, Yoshihiko; Omuro, Yasushi; Tamura, Takao; Doi, Toshihiko; Yukisawa, Seigo; Yasui, Hirofumi; Nagashima, Fumio; Gotoh, Masahiro; Esaki, Taito; Emig, Michael; Chandrawansa, Kumari; Liepa, Astra M; Wilke, Hansjochen; Ichimiya, Yukako; Ohtsu, Atsushi

2016-07-01

We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial. Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m(2) (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations. The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % confidence interval, 0.60-1.28) in the Japanese population and 0.73 (95 % confidence interval, 0.58-0.91) in the Western population. The progression-free survival hazard ratio was 0.50 (95 % confidence interval, 0.35-0.73) in the Japanese population and 0.63 (95 % confidence interval, 0.51-0.79) in the Western population. The objective response rate was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 41.2 % vs 19.4 %; Western population, 26.8 % vs 13.0 %), as was the 6-month survival rate (Japanese population, 94.1 % vs 71.4 %; Western population, 66.0 % vs 49.0 %). Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. CLINICALTRIALS. NCT

Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes.

PubMed

Sato, Junko; Kanazawa, Akio; Ikeda, Fuki; Yoshihara, Tomoaki; Goto, Hiromasa; Abe, Hiroko; Komiya, Koji; Kawaguchi, Minako; Shimizu, Tomoaki; Ogihara, Takeshi; Tamura, Yoshifumi; Sakurai, Yuko; Yamamoto, Risako; Mita, Tomoya; Fujitani, Yoshio; Fukuda, Hiroshi; Nomoto, Koji; Takahashi, Takuya; Asahara, Takashi; Hirose, Takahisa; Nagata, Satoru; Yamashiro, Yuichiro; Watada, Hirotaka

2014-08-01

Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

PubMed Central

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-01-01

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection.

PubMed

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-07-21

To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal metaplasia score of

Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients.

PubMed

Tofuku, Yukari; Nobeyama, Yoshimasa; Kamide, Ryoichi; Moriwaki, Shinichi; Nakagawa, Hidemi

2015-09-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient's fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30-50 years in XP-F patients. © 2015 Japanese Dermatological Association.

Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis

PubMed Central

Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

2016-01-01

Abstract Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile. PMID:26472043

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

PubMed

Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

2017-12-01

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

Trust in One’s Physician: The Role of Ethnic Match, Autonomy, Acculturation, and Religiosity Among Japanese and Japanese Americans

PubMed Central

Tarn, Derjung M.; Meredith, Lisa S.; Kagawa-Singer, Marjorie; Matsumura, Shinji; Bito, Seiji; Oye, Robert K.; Liu, Honghu; Kahn, Katherine L.; Fukuhara, Shunichi; Wenger, Neil S.

2005-01-01

PURPOSE Trust is a cornerstone of the physician-patient relationship. We investigated the relation of patient characteristics, religiosity, acculturation, physician ethnicity, and insurance-mandated physician change to levels of trust in Japanese American and Japanese patients. METHODS A self-administered, cross-sectional questionnaire in English and Japanese (completed in the language of their choice) was given to community-based samples of 539 English-speaking Japanese Americans, 340 Japanese-speaking Japanese Americans, and 304 Japanese living in Japan. RESULTS Eighty-seven percent of English-speaking Japanese Americans, 93% of Japanese-speaking Japanese Americans, and 58% of Japanese living in Japan responded to trust items and reported mean trust scores of 83, 80, and 68, respectively, on a scale ranging from 0 to 100. In multivariate analyses, English-speaking and Japanese-speaking Japanese American respondents reported more trust than Japanese respondents living in Japan (P values <.001). Greater religiosity (P <.001), less desire for autonomy (P <.001), and physician-patient relationships of longer duration (P <.001) were related to increased trust. Among Japanese Americans, more acculturated respondents reported more trust (P <.001), and Japanese physicians were trusted more than physicians of another ethnicity. Among respondents prompted to change physicians because of insurance coverage, the 48% who did not want to switch reported less trust in their current physician than in their former physician (mean score of 82 vs 89, P <.001). CONCLUSIONS Religiosity, autonomy preference, and acculturation were strongly related to trust in one’s physician among the Japanese American and Japanese samples studied and may provide avenues to enhance the physician-patient relationship. The strong relationship of trust with patient-physician ethnic match and the loss of trust when patients, in retrospect, report leaving a preferred physician suggest unintended

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

PubMed

Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

2016-09-01

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

The Impact of Laparoscopic Sleeve Gastrectomy with Duodenojejunal Bypass on Intestinal Microbiota Differs from that of Laparoscopic Sleeve Gastrectomy in Japanese Patients with Obesity.

PubMed

Kikuchi, Rieko; Irie, Junichiro; Yamada-Goto, Nobuko; Kikkawa, Eri; Seki, Yosuke; Kasama, Kazunori; Itoh, Hiroshi

2018-06-01

Bariatric surgery improves metabolic diseases and alters the intestinal microbiota in animals and humans, but different procedures reportedly have different impacts on the intestinal microbiota. We developed laparoscopic sleeve gastrectomy with duodenojejunal bypass (LSG-DJB) as an alternative to laparoscopic Roux-en-Y gastric bypass (LRYGB) in addition to laparoscopic sleeve gastrectomy (LSG) for Japanese patients with obesity. We investigated the precise change in the intestinal microbiota induced by these procedures in the present study. A prospective observational study of 44 Japanese patients with obesity was conducted [22 patients underwent LSG, 18 underwent LSG-DJB, and 4 underwent laparoscopic adjustable gastric banding (LAGB)]. The patients' clinical parameters and intestinal microbiota were investigated before and for 6 months after surgery. The microbiota was analyzed by a 16S rDNA method. LSG and LSG-DJB significantly improved the metabolic disorders in the patients with obesity. The proportion of the phylum Bacteroidetes and order Lactobacillales increased significantly in the LSG group, and that of the order Enterobacteriales increased significantly in the LSG-DJB group. LSG and LSG-DJB improved obesity and type 2 diabetes in Japanese patients with obesity, but the impact of LSG-DJB on the intestinal microbiota differed from that of LSG. This difference in the impact on the intestinal environment could explain the different efficacies of LSG and LSG-DJB in terms of their ability to resolve metabolic disorders in the clinical setting.

[Efficacy evaluation of lafutidine for mild reflux esophagitis in Japanese patients].

PubMed

Ohara, Shuichi; Haruma, Ken; Kinoshita, Yoshikazu; Kusano, Motoyasu

2010-04-01

To evaluate the efficacy of lafutidine (20mg) , famotidine (40mg) and placebo in patients with mild reflux esophagitis (Grades A and B according to the Los Angeles classification) , a double-blind, multicenter, randomized clinical trial was performed for the first time in Japanese patients. In addition to each physician's evaluation, efficacy was evaluated by judging panels using images submitted by each physician. The healing rate after 8 weeks for lafutidine, famotidine and placebo were 67.7%, 56.6% and 41.2%, respectively. Lafutidine was significantly more effective than placebo (p=0.002, according to the judging panels) . Based on the evaluation of endoscopic images by the judging panels, 91 (27.1%) of 336 images submitted by each physician were judged to not be mucosal breaks. Judging panels are considered one of the ways to resolve the problem of the need to unify the criteria.

Applying Japanese management tips to patient accounts.

PubMed

Groenevelt, C J

1990-04-01

"Just in time," a Japanese management philosophy that has been applied successfully in manufacturing operations, also can be used to improve management of patient accounts departments. Under its principles, healthcare organizations would develop standardized procedures; involve workers in decision making; set up training and education programs aimed at creating a multi-skilled pool of workers; establish smooth production schedules; and foster cooperation and commitment to the philosophy throughout the organization.

Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes.

PubMed

Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa

Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H 2 S) levels in patients with type 2 diabetes, as the plasma H 2 S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H 2 S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H 2 S levels were measured using the methylene blue assay. The plasma H 2 S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H 2 S levels (45.115.5 M versus 54.026.4 M, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H 2 S levels and the HbA1c levels (=-0.505, p<0.01), Furthermore, a reduction in the plasma H 2 S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.913.8 M versus 47.515.9 M, p<0.01). Conclusion Collectively, the plasma H 2 S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549).

The clinical practice of high-flow nasal cannula oxygen therapy in adults: A Japanese cross-sectional multicenter survey.

PubMed

Ito, Jiro; Nagata, Kazuma; Sato, Susumu; Shiraki, Akira; Nishimura, Naoki; Izumi, Shinyu; Tachikawa, Ryo; Morimoto, Takeshi; Tomii, Keisuke

2018-05-01

High-flow nasal cannula oxygen therapy (HFNC) is widely used mainly in the acute care setting, but limited data are available on real-world practice in adults. The objective of this study was to describe HFNC practices in Japanese adults. A retrospective cross-sectional multicenter survey of adult patients receiving HFNC from January through March 2015 was conducted in 33 participating hospitals in Japan. We obtained information on 321 patients (median age, 76; 218 men, 103 women; median estimated PaO 2 /F I O 2, 178 mm Hg) from 22 hospitals. Do-not-intubate status was determined in 37.4% of patients. Prior to HFNC, 57.9% of patients received conventional oxygen therapy; 25.9%, noninvasive ventilation; and 15.0%, invasive mechanical ventilation. The common indications for HFNC were acute hypoxemic respiratory failure (ARF) (65.4%), postoperative respiratory support (15.9%), and post-extubation respiratory support (11.2%). The underlying etiology of ARF included interstitial lung disease, pneumonia, and cardiogenic pulmonary edema. HFNC was administered mostly in intensive care units or intermittent care units (60.7%) and general wards (36.1%). Median duration of HFNC was 4 days; median total flow rate, 40 L/min; and median F I O 2 , 50%. HFNC significantly improved PaO 2 , PaCO 2 , SpO 2 and respiratory rate from baseline. Two-thirds of patients finally survived to be discharged or transferred. We documented patient demographics, clinical indications, and settings of HFNC use in the real world. We also demonstrated positive effects of HFNC on respiratory parameters. Further studies are urgently needed regarding the efficacy and safety of HFNC in populations outside of previous clinical trials. Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

PubMed

Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

2016-01-01

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients.

PubMed

Sonoda, Nao; Morimoto, Akiko; Ugi, Satoshi; Morino, Katsutaro; Sekine, Osamu; Nemoto, Ken-Ichi; Godai, Kayo; Maegawa, Hiroshi; Miyamatsu, Naomi

2015-01-01

The objective of this study was to explore predictors, including social factors, lifestyle factors, and factors relevant to glycemic control and treatment, for mild and severe hypoglycemia in insulin-treated Japanese diabetic patients. This study included 123 insulin-treated diabetic patients who were referred to the diabetes clinic between January and July 2013 at Shiga University of Medical Science Hospital. After a survey examining the various factors, patients were followed for 6 months. During the follow-up period, blood glucose was self-monitored. Mild hypoglycemia was defined as blood glucose level 50-69 mg/dl, and severe hypoglycemia was defined as blood glucose level ≤49 mg/dl. Multinomial logistic regression was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of each factor for mild and severe hypoglycemia. During the 6-month follow-up period, 41 (33.3%) patients experienced mild hypoglycemia, and 20 (16.3%) experienced severe hypoglycemia. In multivariable-adjusted analyses, assistance from family members at the time of the insulin injection [presence/absence, OR (95% CI): 0.39 (0.16-0.97)] and drinking [current drinker/non- and ex-drinker, OR (95% CI): 4.89 (1.68-14.25)] affected mild hypoglycemia. Assistance from family members at the time of insulin injection [presence/absence, OR (95% CI): 0.19 (0.05-0.75)] and intensive insulin therapy [yes/no, OR (95% CI): 3.61 (1.06-12.26)] affected severe hypoglycemia. In conclusion, our findings suggest that not only a factor relevant to glycemic control and treatment (intensive insulin therapy) but also a social factor (assistance from family members) and a lifestyle factor (current drinking) were predictors for mild or severe hypoglycemia in Japanese insulin-treated diabetic patients.

Association between SCO2 mutation and extreme myopia in Japanese patients.

PubMed

Wakazono, Tomotaka; Miyake, Masahiro; Yamashiro, Kenji; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

2016-07-01

To investigate the role of SCO2 in extreme myopia of Japanese patients. In total, 101 Japanese patients with extreme myopia (axial length of ≥30 mm) OU at the Kyoto University Hospital were included in this study. Exon 2 of SCO2 was sequenced by conventional Sanger sequencing. The detected variants were assessed using in silico prediction programs: SIFT, PolyPhen-2 and MutationTaster. To determine the frequency of the mutations in normal subjects, we referred to the 1000 Genomes Project data and the Human Genetic Variation Database (HGVD) in the Human Genetic Variation Browser. The average age of the participants was 62.9 ± 12.7 years. There were 31 males (30.7 %) and 70 females. Axial lengths were 31.76 ± 1.17 mm OD and 31.40 ± 1.07 mm OS, and 176 eyes (87.6 %) out of 201 eyes had myopic maculopathy of grade 2 or more. Among the 101 extremely myopic patients, one mutation (c.290 C > T;p.Ala97Val) in SCO2 was detected. This mutation was not found in the 1000 Genomes Project data or HGVD data. Variant type of the mutation was nonsynonymous. Although the SIFT prediction score was 0.350, the PolyPhen-2 probability was 0.846, thus predicting its pathogenicity to be possibly damaging. MutationTaster PhyloP was 1.268, suggesting that the mutation is conserved. We identified one novel possibility of an extreme myopia-causing mutation in SCO2. No other disease-causing mutation was found in 101 extremely myopic Japanese patients, suggesting that SCO2 plays a limited role in Japanese extreme myopia. Further investigation is required for better understanding of extreme myopia.

The effects of illness beliefs and chemotherapy impact on quality of life in Japanese and Dutch patients with breast or lung cancer.

PubMed

van der Kloot, Willem A; Uchida, Yuka; Inoue, Kenichi; Kobayashi, Kunihiko; Yamaoka, Kazue; Nortier, Hans W R; Kaptein, Ad A

2016-02-01

Responses to diagnosis and treatment of cancer are mediated by a patient's illness perceptions. Such perceptions, though different among individuals, may be culturally dependent, and act upon health related quality of life (HRQOL). Over time, individual patients show different types of response trajectories. Four issues were investigated: (I) country and disease differences in illness beliefs between Japanese and Dutch patients with lung or breast cancer; (II) country and disease differences in HRQOL in early chemotherapy; (III) individual, country, and disease differences among HRQOL trajectories; (IV) the impact of illness beliefs on HRQOL trajectories. A total of 89 Japanese and Dutch patients with lung or breast cancer cooperated immediately before, one week after, and eight weeks after the start of chemotherapy. Data included the EORTC QLQ-C30 quality of life (QL) questionnaire and the Brief Illness Perception Questionnaire (B-IPQ). EORTC QLQ-C30 scales were summarized by two dimensions: generalized quality of life (GENQOL) and psychological well-being (PSYQOL). (I) Japanese patients had higher means on B-IPQ's concern and time line than Dutch patients. Japanese lung cancer patients had a higher mean on treatment control than all other patients; (II) no differences between country and cancer type occurred on the two HRQOL dimensions. First assessment HRQOL differed significantly from the second and third assessments without differences between the latter two. Between the first two assessments, a decrease in GENQOL occurred, together with an improvement in PSYQOL; (III) individual differences dominated the trajectories; (IV) negative beliefs usually coincided with lower scores on GENQOL and PSYQOL. Patients initially lower on PSYQOL generally showed larger improvement. Individual differences in HRQOL dominate differences between culture and cancer type, and illness beliefs influence HRQOL changes in individual patients. Clinical application is possible through

Profile of saxagliptin in the treatment of type 2 diabetes: focus on Japanese patients.

PubMed

Konya, Hiroyuki; Yano, Yuzo; Matsutani, Satoshi; Tsunoda, Taku; Ikawa, Takashi; Kusunoki, Yoshiki; Matsuo, Toshihiro; Miuchi, Masayuki; Katsuno, Tomoyuki; Hamaguchi, Tomoya; Miyagawa, Jun-Ichiro; Namba, Mitsuyoshi

2014-01-01

Saxagliptin is a selective and potent dipeptidyl peptidase (DPP)-4 inhibitor, approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM) in the USA on July 2009, and had been launched globally in over 86 countries by September 2013. In patients with T2DM, once-daily administration of saxagliptin before breakfast achieves sustained inhibition of plasma DPP-4 activity and reduction of postprandial hyperglycemia, including after dinner, associated with an increase in plasma glucagon-like peptide-1 levels. This paper reviews the safety and efficacy of saxagliptin in Japanese patients with T2DM. The clinical development study in Japan supported its usefulness for the disease. Saxagliptin 1, 2.5, and 5 mg led to significant improvements in glycated hemoglobin (HbA1c), and was generally well tolerated. Treatment with saxagliptin 5 mg induced a sustained reduction in HbA1c over 52 weeks. Long-term combination therapy with saxagliptin and other oral hypoglycemic agents also provided sustained glycemic control and was well tolerated for up to 52 weeks. Saxagliptin as add-on to sulfonylureas or glinides has a tendency to increase hypoglycemia, but not with other oral antidiabetic agents, such as α-glucosidase inhibitors, metformin, or thiazolidinediones. The results of clinical trials have confirmed the long-term efficacy and safety of saxagliptin monotherapy as well as its use as add-on combination therapy, and support its usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for hypoglycemia and weight gain, which often becomes problematic in routine care of T2DM. Meta-analysis of clinical trials in the USA showed no evidence of increased risk of cardiovascular events associated with saxagliptin, suggesting the superior of saxagliptin in terms of safety. Recently, investigators in the SAVOR-TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in

Investigation into the plasma concentration of ω3 polyunsaturated fatty acids in Japanese attention-deficit hyperactivity disorder patients.

PubMed

Yonezawa, Ken; Nonaka, Shunsuke; Iwakura, Yuka; Kusano, Yuka; Funamoto, Yuko; Kanchi, Nobukazu; Yamaguchi, Naohiro; Kusumoto, Yuko; Imamura, Akira; Ozawa, Hiroki

2018-06-20

Several studies report that patients with attention-deficit hyperactivity disorder (ADHD) have a low plasma concentration of polyunsaturated fatty acids (PUFAs). Since fish intake varies among countries and is high in Japan, those results may not apply to Japanese patients with ADHD. However, there is currently not enough evidence to support this. We compared the plasma PUFAs levels of patients with ADHD with the standard reference levels for healthy subjects, and examined the relationship between those PUFAs levels and the subject's psychological evaluation. The subjects were 24 patients (age < 20 years) previously diagnosed with ADHD (according to the DSM-IV-TR criteria) at the psychiatric department of the Nagasaki University Hospital, between November 2010 and November 2015. The plasma concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) were measured using gas chromatography. Data pertaining to global assessment of functioning (GAF), clinical global impressions, ADHD Rating Scale-IV, and the drug used for treatment (atomoxetine or methylphenidate) were obtained from the medical records. The plasma concentrations of DHA, EPA, and EPA/AA were significantly lower than the normal reference range, indicating that ADHD patients present an imbalance in PUFAs levels. This trend is similar to ADHD patients in other countries and replacement therapy in Japanese ADHD patients may be useful.

Social support and psychological and physical states among Japanese patients with breast cancer and their spouses prior to surgery.

PubMed

Makabe, Reiko; Nomizu, Tadashi

2006-05-03

To assess social support and psychological and physical states among Japanese patients with breast cancer and their spouses prior to surgery. Descriptive, comparative, and correlational. A general hospital in northern Japan. 38 Japanese patients with breast cancer and their spouses (N = 76). The Japanese versions of three questionnaires were used to collect data before surgery: the Interpersonal Relationship Inventory, the General Health Questionnaire, and the Physical States Interview Form. Social support (support, conflict, and reciprocity), social network, and psychological and physical states. Significant differences were found in support and reciprocity between patients and their spouses. However, no significant differences were found in social network, conflict, or psychological states between patients and their spouses. Moreover, some significant correlations were found in the variables of conflict, social network, and psychological and physical states. Japanese patients with breast cancer perceived more support and reciprocity than their spouses before their breast surgery. Conflict was significantly correlated with psychological states among Japanese women with breast cancer and their spouses. Healthcare professionals need to consider social support as an important factor to help Japanese patients with breast cancer and their spouses cope with the disease.

Clinical Ethics Consultation: Examining how American and Japanese experts analyze an Alzheimer's case

PubMed Central

Nagao, Noriko; Aulisio, Mark P; Nukaga, Yoshio; Fujita, Misao; Kosugi, Shinji; Youngner, Stuart; Akabayashi, Akira

2008-01-01

Background Few comparative studies of clinical ethics consultation practices have been reported. The objective of this study was to explore how American and Japanese experts analyze an Alzheimer's case regarding ethics consultation. Methods We presented the case to physicians and ethicists from the US and Japan (one expert from each field from both countries; total = 4) and obtained their responses through a questionnaire and in-depth interviews. Results Establishing a consensus was a common goal among American and Japanese participants. In attempting to achieve consensus, the most significant similarity between Japanese and American ethics consultants was that they both appeared to adopt an "ethics facilitation" approach. Differences were found in recommendation and assessment between the American and Japanese participants. In selecting a surrogate, the American participants chose to contact the grandson before designating the daughter-in-law as the surrogate decision-maker. Conversely the Japanese experts assumed that the daughter-in-law was the surrogate. Conclusion Our findings suggest that consensus building through an "ethics facilitation" approach may be a commonality to the practice of ethics consultation in the US and Japan, while differences emerged in terms of recommendations, surrogate assessment, and assessing treatments. Further research is needed to appreciate differences not only among different nations including, but not limited to, countries in Europe, Asia and the Americas, but also within each country. PMID:18226273

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study.

PubMed

Yamazaki, Naoya; Kiyohara, Yoshio; Uhara, Hisashi; Uehara, Jiro; Fujimoto, Manabu; Takenouchi, Tatsuya; Otsuka, Masaki; Uchi, Hiroshi; Ihn, Hironobu; Minami, Hironobu

2017-06-01

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema.

PubMed

Nemoto-Hasebe, I; Akiyama, M; Nomura, T; Sandilands, A; McLean, W H I; Shimizu, H

2009-12-01

Mutations in the gene encoding filaggrin (FLG) have been shown to predispose to atopic eczema (AE). Further to establish population genetics of FLG mutations in the Japanese population and to elucidate effects of FLG mutations to filaggrin biosynthesis in skin of patients with AE. We searched for FLG mutations in 19 newly recruited Japanese patients with AE. We then screened 137 Japanese patients with AE and 134 Japanese control individuals for a novel mutation identified in the present study. In addition, we evaluated FLG mRNA expression by real-time reverse transcription-polymerase chain reaction and profilaggrin/filaggrin protein expression by immunohistochemical staining in the epidermis of the patients carrying the novel mutation. We identified a novel FLG nonsense mutation c.12069A>T (p.Lys4021X) in one patient with AE. Upon further screening, p.Lys4021X was identified in four patients with AE (2.9% of all the patients with AE). In total, there are at least eight FLG variants in the Japanese population. Here we show that about 27% of patients in our Japanese AE case series carry one or more of these eight FLG mutations and these variants are also carried by 3.7% of Japanese general control individuals. There is a significant statistical association between the eight FLG mutations and AE (chi(2) P = 6.50 x 10(-8)). Interestingly, the present nonsense mutation is in the C-terminal incomplete filaggrin repeat and is the mutation nearest the C-terminal among previously reported FLG mutations. Immunohistochemical staining for filaggrin revealed that this nonsense mutation leads to remarkable reduction of filaggrin protein expression in the patients' epidermis. We clearly demonstrated that FLG mutations are significantly associated with AE in the Japanese population. The present results further support the hypothesis that the C-terminal region is essential for proper processing of profilaggrin to filaggrin.

Japanese version of the Dermatology Life Quality Index: validity and reliability in patients with acne.

PubMed

Takahashi, Natsuko; Suzukamo, Yoshimi; Nakamura, Motonobu; Miyachi, Yoshiki; Green, Joseph; Ohya, Yukihiro; Finlay, Andrew Y; Fukuhara, Shunichi

2006-08-03

Patient-reported quality of life is strongly affected by some dermatologic conditions. We developed a Japanese version of the Dermatology Life Quality Index (DLQI-J) and used psychometric methods to examine its validity and reliability. The Japanese version of the DLQI was created from the original (English) version, using a standard method. The DLQI-J was then completed by 197 people, to examine its validity and reliability. Some participants completed the DLQI-J a second time, 3 days later, to examine the reproducibility of their responses. In addition to the DLQI-J, the participants completed parts of the SF-36 and gave data on their demographic and clinical characteristics. Their physicians provided information on the location and clinical severity of the skin disease. The participants reported no difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2% were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD: 3.99). The responses were found to be reproducible and stable. Results of principal-component and factor analysis suggested that this scale measured one construct. The correlations of DLQI-J scores with sex or age were very poor, but those with SF-36 scores and with clinical severity were high. The DLQI-J provides valid and reliable data despite having only a small number of items.

Diagnostic utility of combined retinal ganglion cell count estimates in Japanese glaucoma patients.

PubMed

Sakamoto, Mari; Mori, Sotaro; Ueda, Kaori; Akashi, Azusa; Inoue, Yukako; Kurimoto, Takuji; Kanamori, Akiyasu; Yamada, Yuko; Nakamura, Makoto

2018-01-01

To assess the combined estimate of retinal ganglion cell (RGC) count developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese patients. Cross-sectional study. Thirty-one eyes of 19 healthy controls and 106 eyes of 70 glaucoma patients underwent standard automated perimetry (SAP) and three types of spectral domain optical coherence tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC counts derived from SAP and SD-OCT data were estimated using the Harwerth model (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates (CRGC) were calculated using the formula developed by Medeiros et al. Receiver operating characteristic curve (ROC) analyses were conducted for mean deviation (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC. The mean OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245, and 1316 (× 1000 cells), respectively, for the control group and 463, 519, and 516 (× 1000 cells), respectively, for the patient group. SAPrgc of the controls' group was 1526 and the patients' group, 731 (× 1000 cells), and were consistently greater than OCTrgc in both groups (a generalized estimating equation model, p < 0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196, 0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device used or glaucoma severity. CRGC proved well suited to discriminate glaucoma patients from controls. However, its clinical utility did not seem to overwhelm isolated structural measures in the tested Japanese patients.

Elderly Japanese emigrants to Brazil before World War II: I. Clinical profiles based on specific historical background.

PubMed

Meguro, M; Meguro, K; Caramelli, P; Ishizaki, J; Ambo, H; Chubaci, R Y; Hamada, G S; Nitrini, R; Yamadori, A

2001-08-01

To research the demographic and clinical profiles of elderly Japanese emigrants, who arrived in Brazil before World War II, in order to give them appropriate psychogeriatric care. Elderly Japanese immigrants aged 65 years and over, belonging to the Miyagi Association in the São Paulo Metropolitan Area, were targeted. They emigrated from Miyagi Prefecture to Brazil and are now living in the area. We were able to interview 166 respondents. All data were gathered using standardized interview methods covering (a) free interview about the immigration history, (b) demographics, and (c) physical status. Through the free interview, we found their immigration histories, which affected their clinical profiles. The mean age and educational level were 77.5 years and 6.3 years, respectively. Sixty per cent of them immigrated when they were younger than 14. Ninety-four per cent of them still keep Japanese nationality. Fifty-seven per cent of them usually use Japanese, while 10% of them use Portuguese. Although their emigration histories were hard, 76% of them perceived their health as being excellent or relatively good. The percentages of subjects with histories of disease were hypertension, 52.5%; cardiac disease, 20.8%; diabetes mellitus, 24.2%; and hyperlipidemia, 25.0%, which were affected by the Brazilian environment. The elderly Japanese who emigrated to Brazil before World War II have a unique historical and demographic background. Their clinical profiles cannot be fully understood without knowing their histories. They definitely need high quality international psychogeriatric care. Copyright 2001 John Wiley & Sons, Ltd.

Peginterferon Alfa-2a plus Ribavirin in Japanese Patients Infected with Hepatitis C Virus Genotype 2 Who Failed Previous Interferon Therapy

PubMed Central

Kanda, Tatsuo; Nakamoto, Shingo; Nishino, Takayoshi; Takada, Nobuo; Tsubota, Akihito; Kato, Keizo; Miyamura, Tatsuo; Maruoka, Daisuke; Wu, Shuang; Tanaka, Takeshi; Arai, Makoto; Mikami, Shigeru; Fujiwara, Keiichi; Imazeki, Fumio; Yokosuka, Osamu

2013-01-01

Some patients infected with hepatitis C virus (HCV) genotype 2 could be cured with treatment shorter than 24 weeks using peginterferon plus ribavirin, but there are still treatment-refractory patients. Direct-acting antivirals (DAAs) are not currently available for HCV genotype 2 patients, different from genotype 1 patients, in clinical practice. We investigated 29 HCV genotype 2-infected Japanese patients who had been previously treated and failed to clear HCV. We retreated them with peginterferon alfa-2a plus ribavirin and measured HCV RNA level to assess the efficacy and safety of this treatment in patients who had failed previous therapy. We found that retreatment of HCV genotype 2-infected Japanese patients with peginterferon alfa-2a plus ribavirin for 24-48 weeks led to 60 to 66.6% sustained virological response (SVR) in patients previously treated with (peg-)interferon monotherapy and to 69.9% SVR in relapsers previously treated with peginterferon plus ribavirin. Attention should be paid to certain patients with unique features. Selection of patients according to their previous treatment could lead to optimal therapy in HCV genotype 2 treatment-experienced patients. PMID:23289004

Travel-related health problems in Japanese travelers.

PubMed

Mizuno, Yasutaka; Kudo, Koichiro

2009-09-01

Although the number of Japanese individuals traveling abroad has increased steadily, reaching approximately 17.3 million in 2007, the incidence of various travel-related health problems in Japan remains unknown. The travel-related health problems of Japanese travelers returning to Japan from abroad are analyzed by assessing the records. Data were collected retrospectively on returning travelers who visited the authors' travel clinic during the period from January 2005 through to December 2006 with any health problem acquired overseas. A total of 345 patients were included in this study (200 male, 145 female; average age, 34+/-12.3 years). Reasons for travel included leisure (45.8%); business (39.1%); visiting friends and relatives or accompanying other travelers (8.7%); volunteering (3.8%); and long stays in order to study or live (2.6%). The most visited destination was Asia (n=260), followed by Africa (n=105). The most commonly reported health problems were gastro-intestinal infections (39.1%), followed by respiratory tract infections (16.2%), animal bites (8.1%), and skin problems (5.8%). Together, malaria and dengue accounted for 10% of diagnoses in 125 febrile patients (36.2%). Although the profile of travel-related health problems in Japanese travelers is similar to that of Western travelers, the characteristics of travel were quite different. Therefore Japanese travel advice should be tailored to suit the Japanese traveler.

Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

PubMed

Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

2012-11-01

Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study.

PubMed

Sada, Ken-ei; Yamamura, Masahiro; Harigai, Masayoshi; Fujii, Takao; Takasaki, Yoshinari; Amano, Koichi; Fujimoto, Shouichi; Muso, Eri; Murakawa, Yohko; Arimura, Yoshihiro; Makino, Hirofumi

2015-11-02

This study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Patients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission). Of 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties. The majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice. University Hospital Medical Information Network Clinical Trials Registry UMIN000001648 . Registered 28 February 2009.

Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

PubMed

Lysaght, Tamra

2017-09-01

In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis

PubMed Central

Morishita, Michiko; Watanabe, Haruki; Yan, Minglu; Zeggar, Sonia; Hiramatsu, Sumie; Ohashi, Keiji; Miyawaki, Yoshia; Katsuyama, Eri; Katsuyama, Takayuki; Takano Narazaki, Mariko; Toyota Tatebe, Noriko; Sunahori Watanabe, Katsue; Kawabata, Tomoko; Sada, Ken-Ei; Wada, Jun

2017-01-01

Objective To assess the safety of azathioprine (AZA) in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods We retrospectively enrolled 67 consecutive AAV patients who had initiated AZA treatment from January 2006 to August 2014 at Okayama University Hospital. We evaluated the development of severe adverse events (AEs), AZA discontinuation due to total AEs (severe AEs included) within 1 year, and AZA-associated risk factors. Results The patients' median age was 70 years old. Forty-nine women and 18 men participated at the initiation of the study. Fifty-eight (87%) patients experienced AEs, and 36 experienced severe AEs (21 hepatic and 11 cytopenic severe AEs). Thirty-one (46%) patients discontinued treatment because of AEs. Abnormal hepatic laboratory test results at the treatment initiation were more frequent in patients with hepatic severe AEs and were associated with treatment discontinuation. The leukocyte and neutrophil counts at the treatment initiation were lower in the patients who discontinued treatment because of cytopenic AEs than in those who continued treatment. Only two patients experienced flare-ups during treatment. Conclusion The AE-associated AZA discontinuation rate in Japanese AAV patients was relatively high. AZA use warrants caution in patients with abnormal hepatic laboratory test results or low leukocyte or neutrophil counts. PMID:28674351

Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients

PubMed Central

Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

2014-01-01

Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393). PMID:25089144

Traditional Japanese medicine daikenchuto improves functional constipation in poststroke patients.

PubMed

Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

2014-01-01

Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393).

Clinical effect of a multidisciplinary team approach to the initial treatment of patients with hospital-acquired bloodstream infections at a Japanese university hospital.

PubMed

Tsukamoto, Hitoshi; Higashi, Takashi; Nakamura, Toshiaki; Yano, Ryoichi; Hida, Yukio; Muroi, Yoko; Ikegaya, Satoshi; Iwasaki, Hiromichi; Masada, Mikio

2014-09-01

Hospital-acquired bloodstream infections (BSIs) are significant causes of mortality, and strategies to improve outcomes are needed. We aimed to evaluate the clinical efficacy of a multidisciplinary infection control team (ICT) approach to the initial treatment of patients with hospital-acquired BSI. A before-after quasiexperimental study of patients with hospital-acquired BSI was performed in a Japanese university hospital. The ICT provided immediate recommendations to the attending physician about appropriate antimicrobial therapy and management after reviewing blood cultures, Gram's stain, final organism, and antimicrobial susceptibility results. The sample included 469 patients with hospital-acquired BSI (n = 210, preintervention group; n = 259, postintervention group). There were no significant differences between the groups in background or microbiologic characteristics. The 30-day mortality was significantly lower and significantly more patients received appropriate antimicrobial therapy in the postintervention group (22.9% vs 14.3%; P = .02 and 86.5% vs 69.0%; P < .001, respectively). Multivariate analysis confirmed that the ICT intervention was significantly associated with appropriate antimicrobial therapy (odds ratio, 2.22; 95% confidence interval, 1.27-3.89) and 30-day mortality (odds ratio, 0.49; 95% confidence interval, 0.25-0.95). A timely multidisciplinary team approach decreases the delay of appropriate antimicrobial treatment and may improve HABSI patient outcomes. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

PubMed Central

Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

2015-01-01

Purpose To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. Conclusion These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese patients with osteoporosis: interim report.

PubMed

Saito, Hitoshi; Kakihata, Hiroyuki; Nishida, Yosuke; Yatomi, Sawako; Nihojima, Shigeru; Kobayashi, Yumiko; Tabata, Hidehiro; Nomura, Makoto

2017-07-01

This large-scale post-marketing surveillance study was conducted to assess the safety and effectiveness of eldecalcitol treatment in patients with osteoporosis in a Japanese clinical setting. A total of 3567 patients with osteoporosis were enrolled and received eldecalcitol 0.75 μg/day for 12 months. For this interim report, 3285 patients were eligible for analysis. Mean age was 74.9 ± 8.7 years; 86.8 % (2854/3285) were women. There were 142 reported adverse drug reactions (ADRs) in 129 patients (3.92 % of the total 3285 patients): the most common were hypercalcemia and increased blood calcium (0.88 %), renal impairment (0.27 %), abdominal discomfort (0.24 %), constipation (0.24 %), and pruritus (0.24 %). The incidence of ADRs was 5.10 % in men and 3.74 % in women. Although 10 serious ADRs were reported in 9 patients (0.27 %), no clinically significant safety issues were identified. Incidence of hypercalcemia or increased blood calcium was 8.47 % in patients with renal impairment and only 0.74 % in patients without renal impairment. At last observation, the incidence of new vertebral and nonvertebral fractures was 2.44 % and 1.70 %, respectively. There was a significant increase in bone mineral density at the lumbar spine and distal radius. The bone turnover markers BAP, serum NTX, urinary NTX, and TRACP-5b were suppressed by eldecalcitol treatment in both sexes. In conclusion, consistent with the findings of the phase III pivotal clinical trial, eldecalcitol was shown to have a favorable safety profile and effectiveness in Japanese patients with osteoporosis. However, periodic measurements of serum calcium were required to prevent occurrence of hypercalcemia during eldecalcitol treatment, especially in patients with renal impairment.

Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations.

PubMed

Nakanishi, Hiroshi; Ohtsubo, Masafumi; Iwasaki, Satoshi; Hotta, Yoshihiro; Usami, Shin-Ichi; Mizuta, Kunihiro; Mineta, Hiroyuki; Minoshima, Shinsei

2011-07-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A. In a recent mutation screening of USH2A in Japanese USH2 patients, we identified 11 novel mutations in 10 patients and found the possible frequent mutation c.8559-2A>G in 4 of 10 patients. To obtain a more precise mutation spectrum, we analyzed further nine Japanese patients in this study. We identified nine mutations, of which eight were novel. This result indicates that the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients. Meanwhile, we did not find the c.8559-2A>G in this study. Haplotype analysis of the c.8559-2G (mutated) alleles using 23 single nucleotide polymorphisms surrounding the mutation revealed an identical haplotype pattern of at least 635 kb in length, strongly suggesting that the mutation originated from a common ancestor. The fact that all patients carrying c.8559-2A>G came from western Japan suggests that the mutation is mainly distributed in that area; indeed, most of the patients involved in this study came from eastern Japan, which contributed to the absence of c.8559-2A>G.

Clinical efficacy, radiographic progression, and safety through 156 weeks of therapy with subcutaneous golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis despite prior methotrexate therapy: final results of the randomized GO-FORTH trial

PubMed Central

Tanaka, Yoshiya; Harigai, Masayoshi; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Yamamoto, Kazuhiko; Miyasaka, Nobuyuki; Koike, Takao; Baker, Daniel; Ishii, Yutaka; Yoshinari, Toru

2016-01-01

Abstract Objective: To evaluate the safety and efficacy of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). Methods: Japanese patients with active RA despite MTX were randomized to placebo + MTX (Group 1, n = 88), golimumab 50 mg + MTX (Group 2, n = 86), or golimumab 100 mg + MTX (Group 3, n = 87). Patients with <20% improvement in swollen/tender joint counts entered early escape at week 16. At week 24, all remaining placebo patients crossed over to golimumab 50 mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Results: ACR20 response rates in Group 1, Group 2, and Group 3 were 67.9, 86.1, and 82.4%, respectively, at week 52 and were maintained through week 104 (87.1, 94.0, and 88.7%) and week 156 (97.1, 94.1, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week 156. Among 257 golimumab-treated patients, 251 (97.7%) had ≥1 AE; 54 (21.0%) had ≥1 serious AE through week 156. Infections were the most common type of AE. Conclusions: Response to golimumab + MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab. PMID:26474192

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

PubMed

Takahashi, Shunji; Kobayashi, Takayuki; Tomomatsu, Junichi; Ito, Yoshinori; Oda, Hisanobu; Kajitani, Tatsuhiro; Kakizume, Tomoyuki; Tajima, Takeshi; Takeuchi, Hiromi; Maacke, Heiko; Esaki, Taito

2017-01-01

Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients. LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status. The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected. LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed. ClinicalTrials.gov NCT01911936.

Pharmacokinetics, pharmacodynamics, tolerability, and safety of exenatide in Japanese patients with type 2 diabetes mellitus.

PubMed

Kothare, Prajakti A; Linnebjerg, Helle; Isaka, Yoshitaka; Uenaka, Kazunori; Yamamura, Ayuko; Yeo, Kwee Poo; de la Peña, Amparo; Teng, Choo Hua; Mace, Kenneth; Fineman, Mark; Shigeta, Hirofumi; Sakata, Yukikuni; Irie, Shin

2008-12-01

In this single-blind, parallel, placebo-controlled study, the pharmacokinetics, pharmacodynamics, tolerability, and safety of subcutaneous exenatide were evaluated in 40 Japanese patients with type 2 diabetes. Patients were allocated to 4 groups and randomized to receive exenatide (n = 8/group) or placebo (n = 2/group), with all receiving placebo on day 1. On day 2, patients received single-dose exenatide (2.5 microg [group A] or 5 microg [groups B, C, and D]) or placebo and then bid on days 3 to 5. On days 6 to 10, groups A and B continued on 2.5 and 5 microg bid; groups C and D received 10 and 15 microg bid, respectively. The last dose was given on the morning of day 10. All adverse events were mild or moderate in severity. Exenatide was generally well tolerated up to 10 microg. Exenatide was well absorbed with a median t(max) of 1.5 hours and mean t((1/2)) of 1.6 hours; exposure increased with dose. Up to 10 microg, exenatide reduced postprandial glucose concentrations in a dose-dependent fashion compared with placebo; decreases were similar for 10 and 15 microg. An E(max) model demonstrated that doses higher than 2.5 microg were necessary for adequate glycemic response. Based on tolerability and pharmacokinetic/pharmacodynamic relationships, 5 and 10 microg exenatide may be considered for further clinical development in Japanese patients with type 2 diabetes.

Study abroad experience is related to Japanese doctors' behavior to see foreign patients.

PubMed

Tamamaki, Kinko; Nishio, Hisahide

2013-04-17

Globalization in Japan involves increases in the number of foreign residents. While there are some English-speaking Japanese doctors that are willing to see foreign patients, many are reluctant to do so. In this study, we attempted to clarify the factors that encourage Japanese doctors to see foreign patients. We conducted a questionnaire survey among medical doctors in Kobe City, Japan. The questionnaire was distributed to 172 doctors, and we received 139 responses. Statistical analysis showed a significant correlation between the frequency of seeing foreign patients and having the experience of studying abroad (p<0.05), confirming our hypothesis. There was also a significant correlation between having the experience of studying abroad and the doctors' self-evaluations of their English ability (p<0.05). There was no significant correlation found, however, between the frequency of seeing foreign patients and that of reading English research articles. These data suggested that the experience of living abroad rather than the exposure to English research articles was more highly correlated with seeing greater numbers of foreign patients. In conclusion, greater exposure to colloquial English was one of the determinants of the doctors' greater willingness to see foreign patients. In the Japanese medical education curriculum, therefore, it would be necessary to offer alternatives to studying abroad for those students who do not have such opportunities.

Frequency and clinical features of patients who attempted suicide by Hara-Kiri in Japan.

PubMed

Kato, Koji; Kimoto, Keitaro; Kimoto, Kousuke; Takahashi, Yuki; Sato, Reiko; Matsumoto, Hideo

2014-09-01

Hara-kiri is a unique Japanese custom, primarily stemming from the manners and customs that a samurai held. The aim of the present study was to investigate the clinical features of individuals who attempted suicide by hara-kiri. We enrolled 647 patients who had attempted suicide. Clinical features were compared between those who had employed hara-kiri and those who had used other methods. 25 of the 647 subjects had attempted suicide by hara-kiri. The ratio of men to women and the proportion of patients with mood disorders were significantly higher in the hara-kiri group than in the other methods group. The average length of stay in either the hospital or in the intensive care unit was also longer in the hara-kiri group than in the other methods group. Hara-kiri is an original Japanese method of attempting suicide, and suicide attempts by hara-kiri may be aimed at maintaining a reputation or taking responsibility. © 2014 American Academy of Forensic Sciences.

Systematic molecular analyses of SHOX in Japanese patients with idiopathic short stature and Leri-Weill dyschondrosteosis.

PubMed

Shima, Hirohito; Tanaka, Toshiaki; Kamimaki, Tsutomu; Dateki, Sumito; Muroya, Koji; Horikawa, Reiko; Kanno, Junko; Adachi, Masanori; Naiki, Yasuhiro; Tanaka, Hiroyuki; Mabe, Hiroyo; Yagasaki, Hideaki; Kure, Shigeo; Matsubara, Yoichi; Tajima, Toshihiro; Kashimada, Kenichi; Ishii, Tomohiro; Asakura, Yumi; Fujiwara, Ikuma; Soneda, Shun; Nagasaki, Keisuke; Hamajima, Takashi; Kanzaki, Susumu; Jinno, Tomoko; Ogata, Tsutomu; Fukami, Maki

2016-07-01

The etiology of idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD) in European patients is known to include SHOX mutations and copy-number variations (CNVs) involving SHOX and/or the highly evolutionarily conserved non-coding DNA elements (CNEs) flanking the gene. However, the frequency and types of SHOX abnormalities in non-European patients and the clinical importance of mutations in the CNEs remains to be clarified. Here, we performed systematic molecular analyses of SHOX for 328 Japanese patients with ISS or LWD. SHOX abnormalities accounted for 3.8% of ISS and 50% of LWD cases. CNVs around SHOX were identified in 16 cases, although the ~47 kb deletion frequently reported in European patients was absent in our cases. Probably damaging mutations and benign/silent substitutions were detected in four cases, respectively. Although CNE-linked substitutions were detected in 15 cases, most of them affected poorly conserved nucleotides and were shared by unaffected individuals. These results suggest that the frequency and mutation spectrum of SHOX abnormalities are comparable between Asian and European patients, with the exception of a European-specific downstream deletion. Furthermore, this study highlights the clinical importance and genetic heterogeneity of the SHOX-flanking CNVs, and indicates a limited clinical significance of point mutations in the CNEs.

A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

PubMed

Shimizu, Toshio; Fukuoka, Kazuya; Takeda, Masayuki; Iwasa, Tutomu; Yoshida, Takeshi; Horobin, Joanna; Keegan, Mitchell; Vaickus, Lou; Chavan, Ajit; Padval, Mahesh; Nakagawa, Kazuhiko

2016-05-01

VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting. VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard 3 + 3 dose-escalation design until disease progression or unacceptable toxicity. Blood samples for pharmacokinetics were collected on Day 1 and 15. The assessments were performed using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response. Nine patients were treated across three dose levels (200-600 mg BID). No dose-limiting toxicities were observed at any dose level. Most frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously reported in non-Japanese subjects. Durable stable disease of approximately 24 weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer). VS-6063 was well tolerated at all dose levels investigated in this first-in-Asian study. These data support the administration of VS-6063 to Japanese subjects at the RP2D in clinical trials involving solid tumor malignancies.

Suboptimal Anticoagulant Management in Japanese Patients with Nonvalvular Atrial Fibrillation Receiving Warfarin for Stroke Prevention.

PubMed

Hirano, Teruyuki; Kaneko, Hirokazu; Mishina, Sari; Wang, Feng; Morita, Satoshi

2017-10-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers). Patients with NVAF receiving oral anticoagulants between February 2013 and June 2015 were identified using a nationwide electronic medical record (EMR) database from 69 hospitals in Japan. Demographics and characteristics of patients, PT-INR, time in therapeutic range (TTR), and frequency in range (FIR) of PT-INR between warfarin maintainers and warfarin switchers were assessed. A total of 1705 patients met inclusion criteria and were examined (1501 warfarin maintainers versus 204 warfarin switchers). CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED scores were comparable between groups. However, these scores were significantly higher among warfarin switchers at the time of switching than at the time of warfarin initiation. Furthermore, TTR and FIR of PT-INR were lower in warfarin switchers than in maintainers. Nevertheless, TTR and FIR were below 50% (PT-INR, 1.6-2.6) in both patient groups. In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Comments on the seven clinical questions & answers in Japanese gastric treatment guidelines of the 4th edition].

PubMed

Xu, J M

2017-03-23

Japanese gastric cancer treatment guidelines of the 4th Edition proposed solutions to 7 clinically contentious questions. However, the solutions to question 1-3 are not complete and may cause ambiguity. In order to avoid the wrong choice of surgical resection, the solutions to question 1-3 should be clearly defined. For question 1-3, we suggest provisos be added such as patients with resectable M1 disease and without any other non-curable factors, after whose status and tumor biological behavior being fully understood and being fully discussed by a multidisciplinary team, can be recommended to receive comprehensive treatment including surgical resection.

Differentiation of Trichophyton rubrum clinical isolates from Japanese and Chinese patients by randomly amplified polymorphic DNA and DNA sequence analysis of the non-transcribed spacer region of the rRNA gene.

PubMed

Yang, Xiumin; Sugita, Takashi; Takashima, Masako; Hiruma, Masataro; Li, Ruoyu; Sudo, Hajime; Ogawa, Hideoki; Ikeda, Shigaku

2009-04-01

Trichophyton rubrum is the most common pathogen causing dermatophytosis worldwide. Recent genetic investigations showed that the microorganism originated in Africa and then spread to Europe and North America via Asia. We investigated the intraspecific diversity of T. rubrum isolated from two closely located Asian countries, Japan and China. A total of 150 clinical isolates of T. rubrum obtained from Japanese and Chinese patients were analyzed by randomly amplified polymorphic DNA (RAPD) and DNA sequence analysis of the non-transcribed spacer (NTS) region in the rRNA gene. RAPD analysis divided the 150 strains into two major clusters, A and B. Of the Japanese isolates, 30% belonged to cluster A and 70% belonged to cluster B, whereas 91% of the Chinese isolates were in cluster A. The NTS region of the rRNA gene was divided into four major groups (I-IV) based on DNA sequencing. The majority of Japanese isolates were type IV (51%), and the majority of Chinese isolates were type III (75%). These results suggest that although Japan and China are neighboring countries, the origins of T. rubrum isolates from these countries may not be identical. These findings provide information useful for tracing the global transmission routes of T. rubrum.

Clinical classification of 103 Japanese patients with Guillain-Barré syndrome.

PubMed

Wakerley, Benjamin R; Kokubun, N; Funakoshi, K; Nagashima, T; Hirata, K; Yuki, N

2016-10-15

Guillain-Barré syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti-ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes. Copyright © 2016. Published by Elsevier B.V.

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study.

PubMed

Kitagawa, Mayumi; Tashiro, Kunio

2005-09-01

To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.

Impact of body mass index on perioperative outcomes of laparoscopic radical nephrectomy in Japanese patients with clinically localized renal cell carcinoma.

PubMed

Miyake, Hideaki; Muramaki, Mototsugu; Tanaka, Kazushi; Takenaka, Atsushi; Fujisawa, Masato

2010-06-01

The aim of this study was to review the association between body mass index (BMI) and perioperative outcomes of laparoscopic radical nephrectomy (LRN) in Japanese patients with renal cell carcinoma (RCC). This study included 108 consecutive Japanese patients undergoing LRN for RCC between April 2001 and March 2009. These patients were divided into the following two groups according to BMI: the non-obese group (n= 58, BMI 25 kg/m(2) or less) and the obese group (n= 50, BMI greater than 25 kg/m(2)). Perioperative outcomes between these two groups were retrospectively compared. There were no significant differences in clinicopathological parameters other than BMI between the non-obese and obese groups. There were no significant differences in operative time, estimated blood loss during LRN, and the incidences of open conversion and postoperative complications between these two groups. In addition, there were no significant differences in parameters related to postoperative recovery, including time to walk, time to oral intake and time until permission for discharge, between these two groups. However, significant trends toward a prolonged operative time (P= 0.0050) and increased blood loss (P= 0.012) during LRN in relation to BMI were documented by linear regression analyses. Although the degree of obesity in patients included in this study was comparatively slight, these findings suggest that LRN can be safely performed for patients with RCC irrespective of BMI. However, the difficulty of LRN may increase with BMI considering the trends toward longer operative time as well as greater blood loss.

Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in Japanese patients: a prospective, open-label study.

PubMed

Momoeda, Mikio; Sasaki, Hidetaka; Tagashira, Eiko; Ogishima, Masayuki; Takano, Yuichi; Ochiai, Kazunori

2014-03-01

Herbal medicine containing Vitex agnus-castus (VAC) extract is widely used by women with premenstrual syndrome (PMS) in Europe, however, in Japan, clinical evidence remains to be determined. This study attempted to investigate the efficacy and safety profiles of VAC extract in Japanese patients with PMS. A multi-center, prospective, open-label, single-arm, phase 3 study was performed in Japanese women with PMS and aged 18-44 years. The patients received Prefemin® (Max Zeller Söhne AG, Romanshorn, Switzerland), containing 20 mg of VAC extract, once daily for three menstrual cycles. The efficacy profile was examined based on the intensity of ten PMS symptoms-irritability, depressed mood, anger, headache, bloating, breast fullness, skin disorder, fatigue, drowsiness, and sleeplessness-recorded by patients via a visual analog scale (VAS). In addition, the responder rate was calculated based on the total VAS score defined by the sum of the VAS scores of the first six symptoms mentioned above. Furthermore, physician's global assessment (PGA) scores were recorded. Adverse events including vital signs and laboratory test values were monitored as safety evaluation. Sixty-nine patients received Prefemin®. After the first menstrual cycle, a statistically significant decrease in total VAS score was observed (P<0.001), and the score continued to diminish for the following two cycles. Each of the ten symptom scores decreased significantly in this manner. In addition, the responder rate increased in a time-dependent manner; the rate at the third menstrual cycle was 91.0%, and almost all of the patients were without symptoms or exhibited only mild symptoms based on PGA. Eight patients exhibited non-serious adverse events, one of which was allergic dermatitis whose causal relationship with VAC was not ruled out. VAC extract improved PMS symptoms in Japanese patients, with no substantial adverse events. This is the first study to report the effect of VAC extract in Japanese

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls.

PubMed

Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

2015-01-01

To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan.

Obstructive sleep apnea syndrome causes a pseudo-Cushing's state in Japanese obese patients with type 2 diabetes mellitus.

PubMed

Tamada, Daisuke; Otsuki, Michio; Kashine, Susumu; Hirata, Ayumu; Onodera, Toshiharu; Kitamura, Tetsuhiro; Shimomura, Iichiro

2013-01-01

Activation of the hypothalamic-pituitary-adrenal axis has been reported in some patients with the obstructive sleep apnea syndrome (OSAS). In current study, we investigated whether OSAS affect the screening test for subclinical Cushing's disease using 0.5 mg overnight dexamethasone suppression test (DST) in Japanese obese diabetic patients with OSAS. Among Japanese obese patients with type 2 diabetes mellitus who had been hospitalized in our department, we selected 20 patients with moderate to severe untreated OSAS (apnea-hypoxia index, AHI, of ≥15 events/hour). All patients underwent 0.5 mg DST. The same test was repeated in patients with positive response of it within a few days after continuous positive airway pressure (CPAP) therapy. We found that five patients showed positive response of DST (25%). Three of these patients continued to use CPAP, and they showed normal response of DST after CPAP therapy. Serum cortisol after 0.5 mg DST measured before CPAP therapy correlated significantly with fasting serum cortisol level (r=0.764, p<0.0001), but not with various clinical parameters, including AHI (p=0.784), body mass index (p=0.984), waist circumference (p=0.957), HbA1c (p=0.261), fasting plasma glucose (p=0.420) and HOMA-IR (p=0.500). Our study show that OSAS causes a pseudo-Cushing's syndrome in obese patients with type 2 diabetes mellitus, which phenomena can be reversed by CPAP therapy.

Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy.

PubMed

Kondo, Hiroyuki; Qin, Minghui; Kusaka, Shunji; Tahira, Tomoko; Hasebe, Haruyuki; Hayashi, Hideyuki; Uchio, Eiichi; Hayashi, Kenshi

2007-03-01

To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features. Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA. Four novel mutations-I18K, K54N, R115L, and IVS2-1G-->A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G-->A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women. These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.

Development of a questionnaire to evaluate asthma control in Japanese asthma patients.

PubMed

Tohda, Yuji; Hozawa, Soichiro; Tanaka, Hiroshi

2018-01-01

The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were -0.78, -0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001). The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients. UMIN000016589. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Differences in K-ras and mitochondrial DNA mutations and microsatellite instability between colorectal cancers of Vietnamese and Japanese patients.

PubMed

Miwata, Tomohiro; Hiyama, Toru; Quach, Duc Trong; Le, Huy Minh; Hua, Ha Ngoc Thi; Oka, Shiro; Tanaka, Shinji; Arihiro, Koji; Chayama, Kazuaki

2014-11-30

The incidence of early-onset (under 50 years of age) colorectal cancer (CRC) in the Vietnamese has been reported to be quite higher than that in the Japanese. To clarify the differences in genetic alterations between Vietnamese and Japanese CRCs, we investigated mutations in K-ras and mitochondrial DNA (mtDNA) and high-frequency microsatellite instability (MSI-H) in the CRCs of Vietnamese and Japanese patients. We enrolled 60 Vietnamese and 233 Japanese patients with invasive CRCs. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections. K-ras mutations were examined with PCR-single-strand conformation polymorphism analysis. mtDNA mutations and MSI-H were examined with microsatellite analysis using D310 and BAT-26, respectively. K-ras mutations were examined in 60 Vietnamese and 45 Japanese CRCs. The frequency of the mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (8 of 24 [33%] vs 5 of 45 [11%], p =0.048). MSI-H was examined in 60 Vietnamese and 130 Japanese CRCs. The frequency of MSI-H in the Vietnamese CRCs was also significantly higher than that in the Japanese CRCs (6 of 27 [22%] vs 10 of 130 [8%], p =0.030). mtDNA mutations were examined in 60 Vietnamese and 138 Japanese CRCs. The frequency of mtDNA mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (19 of 44 [43%] vs 11 of 133 [9%], p <0.001). There were no significant differences in clinicopathologic characteristics, such as age, sex, tumour location, and depth, in terms of tumours with/without each genetic alteration in the CRCs of the Vietnamese and Japanese patients. These results indicate that the developmental pathways of CRCs in the Vietnamese may differ from those of CRCs in the Japanese.

Feasibility and clinical utility of the Japanese version of the Abbey pain scale in Japanese aged care.

PubMed

Takai, Yukari; Yamamoto-Mitani, Noriko; Chiba, Yumi; Kato, Ayako

2014-06-01

Active usage of observational pain scales in Japanese aged-care facilities has not been previously described. Therefore, to examine the feasibility and clinical utility of the Abbey Pain Scale-Japanese version (APS-J), this study examined the interrater reliability of the APS-J among a researcher, nurses, and care workers in aged-care facilities in Japan. This study also aimed to obtain nurses' and care workers' opinions on use of the scale. The following data were collected from 88 residents of two aged-care facilities: demographics, Barthel Index, Folstein Mini-Mental Examination (MMSE), 15-item Geriatric Depression Scale (GDS-15), and APS-J for pain. The researchers, nurses, and care workers independently assessed the residents' pain by using the APS-J, and intraclass correlation coefficients (ICC) for interrater reliability and Cronbach alpha for internal consistency were examined. The ICC between researchers and nurses, researchers and care workers, and nurses and care workers were 0.68, 0.74, and 0.76, respectively. Nurses and care workers were invited for focus group interviews to obtain their opinions regarding APS-J use. During these interviews, nurses and care workers stated that the observational points of APS-J subscales were the criteria they normally used to evaluate residents' pain. Several nurses and care workers reported a gap between the estimated pain intensity and APS-J score. Unclear APS-J criteria, difficulties in observing residents, and insufficient practice guidelines were also reported. Our findings indicate that the APS-J has moderate reliability and clinically utility. To facilitate APS-J usage, education and clinical guidelines for pain management may be required for nurses and care workers. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Complementary and alternative medicine use by visitors to rural Japanese family medicine clinics: results from the international complementary and alternative medicine survey.

PubMed

Shumer, Gregory; Warber, Sara; Motohara, Satoko; Yajima, Ayaka; Plegue, Melissa; Bialko, Matthew; Iida, Tomoko; Sano, Kiyoshi; Amenomori, Masaki; Tsuda, Tsukasa; Fetters, Michael D

2014-09-25

There is growing interest in the use of complementary and alternative medicine (CAM) throughout the world, however previous research done in Japan has focused primarily on CAM use in major cities. The purpose of this study was to develop and distribute a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q) to assess the use of CAM among people who visit rural Japanese family medicine clinics. Using a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q), a cross-sectional survey was conducted in three rural family medicine clinics. All patients and those accompanying patients who met inclusion criteria were eligible to participate. Data were entered into SPSS Statistics and analyzed for use by age, gender, and location. Of the 519 respondents who participated in the project, 415 participants reported CAM use in the past 12 months (80.0%). When prayer is excluded, the prevalence of CAM use drops to 77.3% in the past year, or 403 respondents. The most common forms of CAM used by respondents were pain relief pads (n = 170, 32.8%), herbal medicines/supplements (n = 167, 32.2%), and massage by self or family (n = 166, 32.0%). Female respondents, individuals with higher levels of education, and those with poorer overall health status were more likely to use CAM than respondents without these characteristics. Only 22.8% of CAM therapies used were reported to physicians by survey participants. These data indicate that CAM use in rural Japan is common. The results are consistent with previous studies that show that Japanese individuals are more interested in forms of CAM such as pain relief pads and massage, than in mind-body forms of CAM like relaxation and meditation. Due to the high utilization of certain CAM practices, and given that most CAM users do not disclose their CAM use to their doctors, we conclude that physicians in rural Japan would benefit by asking about CAM use

Psychological profiles and health status in Japanese female patients with systemic lupus erythematosus: the Miyagi Lupus Collaborative Study.

PubMed

Minami, Yuko; Sasaki, Takeshi; Arai, Yumiko; Hosokawa, Toru; Hisamichi, Shigeru

2002-03-01

Psychological factors have been suspected to be associated with the development of systemic lupus erythematosus (SLE) and patient's health status. However, psychological profiles among Japanese patients with SLE have been poorly understood. We started a prospective study of female patients with SLE in 1995. Using the baseline data from 279 patients in this prospective study, we cross-sectionally analyzed the relations of clinical factors and social factors to psychological factors, and the association between psychological factors and mental and physical health status. We used the Japanese notion ikigai as an indicator of mental health, and ambulatory activity as an indicator of their physical health, respectively. To measure psychological factors, the short-form of the Eysenck Personality Questionnaire-Revised (short EPQ-R) and the Multidimensional Health Locus of Control (HLOC) scale were used. Active phase of the disease was significantly related to the neuroticism score in the short EPQ-R. Educational level was inversely related to the scores of powerful others and chance HLOC belief. As for health status, the internal HLOC belief was significantly associated with ikigai, and the chance HLOC belief was inversely associated with ambulatory activity. The scores on the short EPQ-R (Extraversion/Introversion and Neuroticism) were exclusively related to ikigai. This study suggests that psychological factors may have effects on both the development of SLE and patient's health status.

The role of family nutritional support in Japanese patients with type 2 diabetes mellitus.

PubMed

Watanabe, Koin; Kurose, Takeshi; Kitatani, Naomi; Yabe, Daisuke; Hishizawa, Masahiro; Hyo, Takanori; Seino, Yutaka

2010-01-01

We investigated the role of family support in glycemic control by nutritional self-care behavior of Japanese patients with type 2 diabetes. One hundred twelve Japanese out-patients with type 2 diabetes were recruited for the study at Kansai Electric Power Hospital. Interviews were conducted and HbA1c and triglyceride levels were measured. HbA1c levels were significantly related to family nutritional support. Patients under 60 years old with family nutritional support showed significantly lower HbA1c than patients without family support (p<0.05). Female patients with family support showed significantly lower HbA1c than those without family support (p<0.05). In addition, male patients with family support showed significantly lower triglyceride levels than those without family support (p<0.05). In male patients, those who were supported by cooking or buying light meals showed significantly lower HbA1c than those who were supported by advice or encouragement (p<0.05). The frequency of support (every day, 2-3 days, 1 week) showed similar outcomes in glycemic control. Patients who appreciate the support and follow the advice showed lower HbA1c (6.88 +/- 0.22%) than (7.43 +/- 0.23%) patients who appreciate the advice but sometimes feel emotional barriers. Family nutritional support is useful in improving metabolic outcome of diabetic patients. Self-care practice in disease management should be carefully adjusted to the family setting of type 2 diabetic patients. Emotional barriers to family support may affect the metabolic consequences, especially in the Japanese elderly.

[Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients].

PubMed

Naito, Takafumi; Kawakami, Junichi

2015-01-01

Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.

Verification of the sensitivity of functional scores for treatment results - Substantial clinical benefit thresholds for the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).

PubMed

Kasai, Yuichi; Fukui, Mitsuru; Takahashi, Kazuhisa; Ohtori, Seiji; Takeuchi, Daisaku; Hashizume, Hiroshi; Kanamori, Masahiko; Hosono, Noboru; Kanchiku, Tsukasa; Wada, Eiji; Sekiguchi, Miho; Konno, Shinichi; Kawakami, Mamoru

2017-07-01

Validity and reliability of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) had already been verified as the patients' self-rating assessment of low back pain and lumbar spinal disease and, the present study demonstrated the responsiveness of this measure. 192 subjects who were determined by medical instructors of the Japanese Society for Spine Surgery and Related Research were analyzed. They had completed a series of treatment and both surveys before and after the treatment. Authors investigated rates of concordance between assessment by physicians and subjective assessment by patients. The mean, standard deviation, minimum, 25th percentile, median, 75th percentile and maximum values for pre-treatment, post-treatment, and acquired points were calculated, and then, we also investigated the trend between subjective assessment by patients and mean acquired points for each JOABPEQ domain and substantial clinical benefit thresholds for the JOABPEQ. Symptom changes as assessed by physicians did not coincide with those by patients, and acquired points in each JOABPEQ domain were significantly increased with improved self-rating by patients. In addition, patients who rated symptom changes as "slightly improved" showed a mean acquired points of ≥20, and those reporting "improved" showed a 25th percentile points of the acquired points of ≥20 approximately. A significant correlation was noted between the self-rating of patients and acquired points JOABPEQ, suggesting that ≥20 acquired points can be interpreted as substantial clinical benefit thresholds for the JOABPEQ. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Practical issues and lessons learned from multi-regional clinical trials via case examples: a Japanese perspective.

PubMed

Ando, Yuki; Hamasaki, Toshimitsu

2010-01-01

The multi-regional clinical trials (MRCTs) being administered in different regions of the world now play a major role in providing evidence for the efficacy and safety of new drugs amidst the simultaneous global development and worldwide registration of such drugs, in support of the expeditious availability of medical products to patients. However, such trials present considerable challenges as far as quality, design, implementation, analysis, and interpretation are concerned. In this article, we share our observations and lessons learned from the design, implementation, analysis, and interpretation of some MRCTs with case examples. Current Japanese regulatory guidance on MRCTs is introduced along with some suggestions for design, implementation, and interpretation. Copyright © 2010 John Wiley & Sons, Ltd.

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

PubMed

Kawai, H; Akaike, M; Kunishige, M; Inui, T; Adachi, K; Kimura, C; Kawajiri, M; Nishida, Y; Endo, I; Kashiwagi, S; Nishino, H; Fujiwara, T; Okuno, S; Roudaut, C; Richard, I; Beckmann, J S; Miyoshi, K; Matsumoto, T

1998-11-01

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Assessment of Japanese stimulant control law offenders using the Addiction Severity Index--Japanese version: comparison with patients in treatment settings.

PubMed

Watanabe, Takashi; Ogai, Yasukazu; Koga, Takehiro; Senoo, Eiichi; Nakamura, Kazuhiko; Mori, Norio; Ikeda, Kazutaka

2009-12-01

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005-2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The chi(2) and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups.

Application of the COOP/WONCA charts to aged patients with chronic obstructive pulmonary disease: a comparison between Japanese and Chinese populations

PubMed Central

2013-01-01

Background The prevalence of chronic obstructive pulmonary disease (COPD) is similar in Japan and China and is increasing due to high rates of smoking in these countries. Reducing COPD is an important public health issue. The goals of this study were to verify the reliability and validity of the Japanese version of the COOP/WONCA charts, a tool for measuring health status, and to examine the qualitative differences in health status between Japanese and Chinese patients with COPD and between these patients and healthy subjects. Methods From 2008 to 2011, we examined the factors affecting the health status of Japanese and Chinese populations living in six cities. Participants were patients with COPD staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (140 Japanese, 201 Chinese) and healthy subjects (243 Japanese, 199 Chinese), all 50 to 79 years old. Health status was measured by using the COOP/WONCA charts, and basic information such as smoking status and medical history was reported by the participants. Results The Japanese and Chinese versions of the COOP/WONCA charts were shown to be reliable and valid by test-retest, comparison with the SF-36 and respiratory symptoms, and correlation of results obtained from patients and their physicians. Stepwise multiple regression analyses demonstrated that “Physical fitness”, “Daily activities”, and “Social activities” were predicted by COPD status and/or respiratory symptoms; “Feelings” by nationality and respiratory symptoms; “Pain” by sex and respiratory symptoms; and “Overall health” by nationality. When the COOP/WONCA scores were stratified by nationality, age, sex, and COPD status, the difference of each score between the patients and healthy subjects was larger for the Chinese subjects than for the Japanese. The physical, psychosocial activities, and pain scores increased significantly as COPD status worsened in Chinese subjects, whereas these scores

Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2

PubMed Central

Yanagawa, Yoshimaro; Aoki, Tomoyuki; Morimura, Tadashi; Araki, Osamu; Kimura, Takao; Ogiwara, Takayuki; Kotajima, Nobuo; Yanagawa, Masumi; Murakami, Masami

2014-01-01

In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population. PMID:24895636

A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months.

PubMed

Ida, Hiroyuki; Tanaka, Akemi; Matsubayashi, Tomoko; Murayama, Kei; Hongo, Teruaki; Lee, Hak-Myung; Mellgard, Björn

2016-07-01

Enzyme replacement therapy (ERT) with exogenous glucocerebrosidase is indicated to treat symptomatic Gaucher disease (GD), a rare, inherited metabolic disorder. ERT with velaglucerase alfa, which is produced in a human cell line using gene activation technology, was studied in a 12-month phase III trial in Japanese patients with type 1 or 3 GD who were switched from imiglucerase ERT (n=6); the current, open-label, 12-month extension study was designed to assess longer-term safety and efficacy. Two adult and three pediatric patients (aged <18years) were enrolled into the extension study. Every-other-week intravenous infusions were administered for 63-78weeks at average doses between 51.5 and 60.7units/kg. Three non-serious adverse events were considered related to velaglucerase alfa treatment, but no patient discontinued from the study. Six serious but non-drug-related adverse events were reported. No patient tested positive for anti-velaglucerase alfa antibodies. Hemoglobin concentrations, platelet counts, and liver and spleen volumes (normalized to body weight) in these patients were generally stable over a cumulative 24-month period from the baseline of the parent trial. The data suggest that velaglucerase alfa was well tolerated and maintained clinical stability in Japanese GD patients over 2years after switching from imiglucerase. ClinicalTrials.gov identifier NCT01842841. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of ipragliflozin in elderly versus non-elderly Japanese patients with type 2 diabetes mellitus: a subgroup analysis of the STELLA-LONG TERM study.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro; Uno, Satoshi

2018-03-01

This subgroup analysis of STELLA-LONG TERM interim data explored the long-term safety and efficacy of ipragliflozin in non-elderly vs. elderly Japanese type 2 diabetes mellitus (T2DM) patients. STELLA-LONG TERM is an ongoing 3-year prospective surveillance study of Japanese T2DM patients receiving ipragliflozin 50 mg once daily. In this subgroup analysis, patient characteristics, laboratory variables, and adverse drug reactions (ADRs) were compared between non-elderly (<65 years) and elderly (≥65 years) patients. Non-elderly patients had significantly higher body mass index and low-density lipoprotein cholesterol than elderly patients (P < 0.001). The proportion of patients with hemoglobin A1c (HbA1c) <8.0% was significantly higher among elderly patients (P < 0.001). HbA1c, fasting plasma glucose, and body weight significantly decreased from baseline to 3 and 12 months in both groups (all P < 0.05 vs. baseline). The ADR incidence was 10.83% vs. 10.42% in non-elderly and elderly patients. The incidence of skin complications was 0.98% vs. 1.65% and that of renal disorder was 0.47% vs. 0.95% in non-elderly and elderly patients (both P = 0.003). Ipragliflozin was effective in non-elderly and elderly Japanese T2DM patients in a real-world clinical setting. The incidence of renal disorder and skin complications was significantly higher in elderly vs. non-elderly patients.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

PubMed Central

Ueda, Takeshi

2017-01-01

Abstract A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. PMID:28003320

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese male patients with osteoporosis.

PubMed

Kondo, Satoshi; Kakihata, Hiroyuki; Nishida, Yosuke; Furuno, Yuko; Kobayashi, Yumiko; Tabata, Hidehiro; Nomura, Makoto

2018-03-12

We conducted a post-marketing observational study to investigate the safety and effectiveness of eldecalcitol for the treatment of osteoporosis in a Japanese clinical setting. The observation period was 12 months for women and 36 months for men. The final results for the female patients have already been published. In this article, the final results for the male patients are reported. A total of 470 male osteoporosis patients were enrolled. The safety analysis set included 431 patients (mean age, 76.8 years; mean ± SD follow-up period, 631.0 ± 450.3 days), and 175 patients continued treatment throughout the 3-year observational period. Adverse drug reactions (ADRs) were reported in 28 patients (6.49%); the most common ADRs were hypercalcemia (1.16%) and renal impairment (1.16%). Serious ADRs were reported in 5 patients (1.16%). Mean serum calcium was within the normal range throughout the observation period. The cumulative incidence of new vertebral and nonvertebral fractures at 36 months, estimated by Kaplan-Meier analysis, was 10.23 and 4.06%, respectively. At the last observation, mean lumbar spine bone mineral density was 3.49% higher (P < 0.0001) than at baseline, and levels of the bone turnover markers BAP and TRACP-5b were reduced (-14.64%; P = 0.0009, and - 29.51%; P < 0.0001, respectively). In conclusion, the safety and effectiveness of eldecalcitol for the treatment of Japanese male osteoporosis patients was confirmed in clinical practice. Careful monitoring of serum calcium and estimated glomerular filtration rate, both before and during treatment, is necessary to minimize the risk of hypercalcemia and renal impairment while maximizing the effectiveness of eldecalcitol.

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection

PubMed Central

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case. PMID:28791128

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection.

PubMed

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case.

Reliability and validity of TEMPS-A in a Japanese non-clinical population: application to unipolar and bipolar depressives.

PubMed

Matsumoto, Satoko; Akiyama, Tsuyoshi; Tsuda, Hitoshi; Miyake, Yuko; Kawamura, Yoshiya; Noda, Toshie; Akiskal, Kareen K; Akiskal, Hagop S

2005-03-01

In Japan, TEMPS-A has gathered much attention, because Kraepelin's concepts on "fundamental states" of mood disorder and temperaments have been widely respected. TEMPS-A was translated into Japanese (and after the approval of the English back translation by H.S.A.), it was administered to 1391 non-clinical subjects, and 29 unipolar and 30 bipolar patients in remission. Of the non-clinical sample, 426 were readministered the instrument again in 1 month. A control group matched for gender and age was drawn from the non-clinical sample. Regarding test-retest reliability, Spearman's coefficients for depressive, cyclothymic, hyperthymic, irritable and anxious temperaments were 0.79, 0.84, 0.87, 0.81 and 0.87, respectively; regarding internal consistency, Cronbach's alpha coefficients were 0.69, 0.84, 0.79, 0.83 and 0.87, respectively. The unipolar and bipolar groups showed significantly higher depressive, cyclothymic and anxious temperament scores than the control group. Curiously, the bipolar group showed significantly lower hyperthymic score than the control group; irritable temperament scores showed no significant differences. Depressive, cyclothymic, irritable and anxious temperament scores showed significant correlations with each other. Between the unipolar and bipolar groups, there was little difference regarding the temperament scores. Also the inter-temperament correlations showed the same pattern in the unipolar and bipolar groups. The clinically well cohort was 70% male. TEMPS-A showed a high reliability and validity (internal consistency) in a Japanese non-clinical sample. By and large, the hypothesized five temperament structure was upheld. Depressive, cyclothymic and anxious temperaments showed concurrent validity with mood disorder. Irritable temperament may represent a subtype of depressive, cyclothymic or anxious temperaments. There may be a temperamental commonality between unipolar and bipolar disorders. TEMPS-A will open new possibilities for

Views of Japanese patients on the advantages and disadvantages of hemodialysis and peritoneal dialysis.

PubMed

Nakamura-Taira, Nanako; Muranaka, Yoshimi; Miwa, Masako; Kin, Seikon; Hirai, Kei

2013-08-01

The preference for dialysis modalities is not well understood in Japan. This study explored the subjective views of Japanese patients undergoing dialysis regarding their treatments. The participants were receiving in-center hemodialysis (CHD) or continuous ambulatory peritoneal dialysis (CAPD). In Study 1, 34 participants (17 CHD and 17 CAPD) were interviewed about the advantages and disadvantages of dialysis modalities. In Study 2, 454 dialysis patients (437 CHD and 17 CAPD) rated the advantages and disadvantages of CHD and CAPD in a cross-sectional survey. Interviews showed that professional care and dialysis-free days were considered as advantages of CHD, while independence, less hospital visits, and flexibility were considered as advantages of CAPD. Disadvantages of CHD included restriction of food and fluids and unpleasant symptoms after each dialysis session. Catheter care was an additional disadvantage of CAPD. Survey showed that the highly ranked advantages were professional care in CHD and less frequent hospital visits in CAPD, while the highly ranked disadvantages were concerns about emergency and time restrictions in CHD, and catheter care and difficulty in soaking in a bath in CAPD. The total scores of advantages and disadvantages showed that CHD patients subjectively rated their own modality better CHD over CAPD, while CAPD patients had the opposite opinion. The results of this study indicate that the factors affecting the decision-making process of Japanese patients are unique to Japanese culture, namely considering the trouble caused to the people around patients (e.g., families, spouses, and/or caregivers).

Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer.

PubMed

Watanabe, Seishiro; Sasahara, Katsuyuki; Kinekawa, Fumihiko; Uchida, Naohito; Masaki, Tsutomu; Kurokohchi, Kazutaka; Murota, Masayuki; Touge, Tetsuo; Kawauchi, Kazuyoshi; Oda, Syuji; Kuriyama, Shigeki

2002-01-01

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.

A genomewide DNA microsatellite association study of Japanese patients with autoimmune hepatitis type 1.

PubMed

Yokosawa, Shuichi; Yoshizawa, Kaname; Ota, Masao; Katsuyama, Yoshihiko; Kawa, Shigeyuki; Ichijo, Tetsuya; Umemura, Takeji; Tanaka, Eiji; Kiyosawa, Kendo

2007-02-01

Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA class II genes. We previously searched the whole HLA region for AIH susceptibility genes using microsatellite markers and found only HLA-DR/DQ to be a candidate region for this suspected multifactorial disease. As such, the aim of this study was to broaden our search and screen the whole genome for additional genes that might contribute to type 1 AIH susceptibility. Eighty-one patients with type 1 AIH (15 men, 66 women, average age 55.9) and 80 healthy sex- and age-matched Japanese controls were enrolled in this study. We performed a case-control association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. Two markers, one on chromosome 11 (D11S902, Pc = 0.013) and one on chromosome 18 (D18S464, Pc = 0.008), were revealed to have statistically significant associations with AIH. An additional 7 markers (D2S367, D6S309, D9S273, D11S1320, D16S423, D17S938, and D18S68) were also found to be candidate susceptibility regions. In addition, our results showed there were 17 regions that may contain genes of resistance to AIH. No specific markers were detected in HLA-DR4-negative patients, and no differences were seen in the clinical courses of patients (severe versus mild to moderate). This first genomewide scan of Japanese AIH patients revealed at least 26 candidate AIH susceptibility or resistance regions other than HLA class II loci. These results also suggested that the products of several genes interact to determine heritable susceptibility to AIH.

Serum glucose, cholesterol and blood pressure levels in Japanese type 1 and 2 diabetic patients: BioBank Japan.

PubMed

Yokomichi, Hiroshi; Nagai, Akiko; Hirata, Makoto; Kiyohara, Yutaka; Muto, Kaori; Ninomiya, Toshiharu; Matsuda, Koichi; Kamatani, Yoichiro; Tamakoshi, Akiko; Kubo, Michiaki; Nakamura, Yusuke; Yamagata, Zentaro

2017-03-01

Evidence of characteristics of Japanese patients with diabetes from a large-scale population is necessary. Few studies have compared glycaemic controls, complications and comorbidities between type 1 and 2 diabetic patients. This paper focuses on illustrating a clinical picture of Japanese diabetic patients and comparing glycaemic control and prognoses between type 1 and 2 diabetes using multi-institutional data. The BioBank Japan Project enrolled adult type 1 and 2 diabetic patients between fiscal years 2003 and 2007. We have presented characteristics, controls of serum glucose, cholesterol and blood pressure, prevalence of complications and comorbidities and survival curves. We have also shown glycaemic controls according to various individual profiles of diabetic patients. A total of 558 type 1 diabetic patients and 30,834 type 2 diabetic patients participated in this study. The mean glycated haemoglobin A1c was higher in type 1 diabetes than in type 2 diabetes. In the type 1 diabetic patients, the glycated haemoglobin A1c had no consistent trend according to age and body mass index. The Kaplan-Meier estimates represented a longer survival time from baseline with type 1 diabetes than with type 2 diabetes. Compared with type 1 diabetic patients, type 2 diabetic patients had double the prevalence of macrovascular complications. This work has revealed detailed plasma glucose levels of type 1 and 2 diabetic patients according to age, body mass index, blood pressure, serum cholesterol levels and smoking and drinking habits. Our data have also shown that the prognosis is worse for type 2 diabetes than for type 1 diabetes in Japan. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Assessment of Japanese Stimulant Control Law Offenders Using the Addiction Severity Index—Japanese Version: Comparison with Patients in Treatment Settings

PubMed Central

Watanabe, Takashi; Ogai, Yasukazu; Koga, Takehiro; Senoo, Eiichi; Nakamura, Kazuhiko; Mori, Norio; Ikeda, Kazutaka

2009-01-01

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005–2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The χ2 and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups. PMID:20049245

Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population.

PubMed

Nguyen, L T; Uchida, T; Tsukamoto, Y; Kuroda, A; Okimoto, T; Kodama, M; Murakami, K; Fujioka, T; Moriyama, M

2010-08-01

The dupA gene of Helicobacter pylori was suggested to be a risk factor for duodenal ulcer but protective against gastric cancer. The present study aimed to re-examine the role of dupA in H. pylori-infected Japanese patients. We found that dupA status was not associated with any gastroduodenal disease, histological score of chronic gastritis or with the extent of interleukin-8 production from gastric cell lines. These results indicate that dupA is unlikely to be a virulence factor of H. pylori in the Japanese population.

Economic burden of psoriatic patients in Japan: Analysis from a single outpatient clinic.

PubMed

Takahashi, Hidetoshi; Satoh, Katsuhiko; Takagi, Akiyoshi; Iizuka, Hajime

2017-09-01

Topical and systemic agents have dramatically improved the treatment efficacy of psoriasis. Few reports, however, exist describing the economic burden in Japanese psoriatic patients. The aim of the study was to evaluate the total costs as well as cost versus efficacy of topical and systemic treatments of psoriatic patients under the Japanese health insurance system. The retrospective study was performed from the database of our clinic, which is located in Hokkaido Prefecture. Cost and effectiveness of psoriatic patients were evaluated during the 12-month period from April 2015 to March 2016. Data were collected and calculated for the total cost per year, treatment efficacy and cost versus efficacy. The mean total cost of topical corticosteroid treatment was ¥18 184/year and was lowest among the treatments. The systemic treatment with biologics was most expensive and the costs were over ¥400 000/year. Among the topical treatments, calcipotriol/betamethasone dipropionate was most expensive (¥34 693/year). However, cost versus efficacy was not significantly different from that of topical corticosteroid treatments. The cost of secukinumab was highest among all the treatments (¥631 600/year). However, treatment day per cost was lowest of all the psoriasis treatments. Biologics showed the highest cost than topical or systemic treatments. However, they showed most marked efficacy in terms of improving the psoriatic skin lesions. © 2017 Japanese Dermatological Association.

Use of clinical practice guidelines by dentists: findings from the Japanese dental practice-based research network.

PubMed

Kakudate, Naoki; Yokoyama, Yoko; Sumida, Futoshi; Matsumoto, Yuki; Gordan, Valeria V; Gilbert, Gregg H

2017-02-01

The objectives of this study were to: (1) examine differences in the use of dental clinical practice guidelines among Japanese dentists, and (2) identify characteristics associated with the number of guidelines used by participating dentists. We conducted a cross-sectional study consisting of a questionnaire survey in Japan between July 2014 and May 2015. The study queried dentists working in outpatient dental practices who are affiliated with the Dental Practice-Based Research Network Japan (n = 148). They were asked whether they have used each of 15 Japanese dental clinical guidelines. Associations between the number of guidelines used by participants and specific characteristics were analysed via negative binomial regression analysis. The mean number of guidelines used by participating dentists was 2.5 ± 2.9 [standard deviation (SD)]. Rate of use of guidelines showed substantial variation, from 5% to 34% among dentists. The proportion of dentists that used guidelines was the highest among oral medicine specialists, who had the highest proportion for 10 of 15 guidelines. Negative binomial regression analysis identified three factors significantly associated with the number of guidelines used: 'years since graduation from dental school', 'specialty practice' and 'practice busyness'. These results suggest that the use of clinical practice guidelines by Japanese dentists may still be inadequate. Training in the use of the guidelines could be given to dental students as undergraduate education and to young clinicians as continuing education. © 2016 John Wiley & Sons, Ltd.

Risk factors for parastomal hernia in Japanese patients with permanent colostomy.

PubMed

Funahashi, Kimihiko; Suzuki, Takayuki; Nagashima, Yasuo; Matsuda, Satoshi; Koike, Junichi; Shiokawa, Hiroyuki; Ushigome, Mitsunori; Arai, Kenichiro; Kaneko, Tomoaki; Kurihara, Akiharu; Kaneko, Hironori

2014-08-01

Although the definitive risk factors for parastomal hernia development remain unclear, potential contributing factors have been reported from Western countries. The aim of this study was to identify the risk factors for parastomal hernia in Japanese patients with permanent colostomies. All patients who received abdominoperineal resection or total pelvic exenteration at our institution between December 2004 and December 2011 were reviewed. Patient-related, operation-related and postoperative variables were evaluated, in both univariate and multivariate analyses, to identify the risk factors for parastomal hernia formation. Of the 80 patients who underwent colostomy, 22 (27.5 %) developed a parastomal hernia during a median follow-up period of 953 days (range 15-2792 days). Hernia development was significantly associated with increasing patient age and body mass index, a laparoscopic surgical approach and the transperitoneal route of colostomy formation. In the multivariate analysis, the body mass index (p = 0.022), the laparoscopic approach (p = 0.043) and transperitoneal stoma creation (p = 0.021) retained statistical significance. Our findings in Japanese ostomates match those from Western countries: a higher body mass index, the use of a laparoscopic approach and a transperitoneal colostomy are significant independent risk factors for parastomal hernia formation. The precise role of the stoma creation route remains unclear.

Reductions in pulmonary function detected in patients with lymphangioleiomyomatosis: An analysis of the Japanese National Research Project on Intractable Diseases database.

PubMed

Hayashida, Mie; Yasuo, Masanori; Hanaoka, Masayuki; Seyama, Kuniaki; Inoue, Yoshikazu; Tatsumi, Koichiro; Mishima, Michiaki

2016-05-01

In lymphangioleiomyomatosis (LAM), predicting lung disease progression is essential for treatment planning. However, no previous Japanese studies have attempted to predict the reductions in pulmonary function that occur in LAM patients. The data for 89 LAM patients who had undergone ≥3 spirometry tests and whose data had been registered in the Japanese National Research Project on Intractable Diseases database between October 2009 and March 2014 were analyzed after excluding patients who had undergone (1) a lung transplant; (2) mTOR inhibitor treatment; or (3) thoracic drainage, pleurodesis, surgery, or thoracic duct ligation during the study period. The rates of change (slope) in pulmonary parameters were calculated, and their associations with clinical background factors were investigated. Among the whole study population, the median (quartiles) slope of forced expiratory volume in one second (FEV1) was -46.7 (-95.2; -15.0)mL per year. Episodes of conservatively treated pneumothorax during the study period were found to be associated with rapid reductions in FEV1 (% predicted). Pregnancy during the study period was associated with a reduction in FEV1 (% predicted). When the patients were divided into those who exhibited initial FEV1 (% predicted) values of >70% (Group A) and ≤70% (Group B), Group B displayed significantly faster reductions in FEV1 (% predicted) than Group A. LAM patients whose initial FEV1 (% predicted) values are ≤70% subsequently exhibit rapid reductions in their FEV1 values, and hence, require treatment. However, the FEV1 reduction rate varies markedly among individuals and should be monitored in all cases. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Kanzaki, Sayaka; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Onji, Morikazu; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2017-01-01

Objective Macrovascular diseases and urgency incontinence are common among Japanese patients with type 2 diabetes mellitus. However, little evidence exists regarding the association between stroke and urgency incontinence among patients with type 2 diabetes mellitus. We examined the associations between macrovascular complications and urgency incontinence among Japanese patients with type 2 diabetes mellitus. Methods The study subjects were 818 Japanese patients with type 2 diabetes mellitus. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate?" We adjusted our analyses for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was independently positively associated with urgency incontinence, with an adjusted odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between ischemic heart disease or peripheral artery disease and the prevalence of urgency incontinence were not significant. Conclusion In Japanese patients with type 2 diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery disease, was independently positively associated with urgency incontinence.

Clinical characteristics of adult patients with tics and/or Tourette's syndrome.

PubMed

Ohta, Masataka; Kano, Yukiko

2003-12-01

This study was conducted to describe the natural course of tic disorders over a long period of time in Japanese adults patients with Tourette's syndrome (TS) in terms of symptomatology. An extensive literature on TS cases was reviewed selectively and 31 TS patients (mean age: 31.4 years; sex: 28 males and 3 females) at our outpatient clinic were examined. The mean follow-up period of the patients was 7.6 years (SD: 8.1; 0 to 26). All the data available for this study, including medical charts, were examined systematically by two experienced child psychiatrists. The adult patients with tic disorders could be classified into the four groups: group A - tics only, group B - tics + comorbidities, group C - comorbidities only and group D - sub-clinical (remission) cases. Our 31 subjects consisted of 10 patients (32.3%) for group A, 14 (45.2%) for group B, 7 (22.6%) for group C, and 0 for group D. Further investigation into the natural course and clinical characteristics of adult TS needs to be done in order to acquire a better understanding of the broad spectrum of TS and to make improvements to the treatment for this illness.

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

1994-09-01

Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 genemore » region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.« less

Cross-cultural comparison of the Scoliosis Research Society Outcomes Instrument between American and Japanese idiopathic scoliosis patients: are there differences?

PubMed

Watanabe, Kei; Lenke, Lawrence G; Bridwell, Keith H; Hasegawa, Kazuhiro; Hirano, Toru; Endo, Naoto; Cheh, Gene; Kim, Yongjung J; Hensley, Marsha; Stobbs, Georgia; Koester, Linda

2007-11-15

A comparative study. To report a preliminary evaluation of the Scoliosis Research Society Outcomes Instrument (SRS-24) and determine whether differences in baseline scores exist between American and Japanese patients with idiopathic scoliosis. Because the SRS outcomes instrument was primarily introduced for the American population, baseline scores in the Japanese population might differ from the American population. A comparative study using the SRS instrument between American and Japanese patients with idiopathic scoliosis has not been reported. Two comparable groups of 100 idiopathic scoliosis patients before spinal fusion were separated into American (A) and Japanese (J). There were no statistically significant differences between the groups for gender (A: 9 men/91 women vs. J: 13 men/87 women), age (A: 15.0 +/- 2.4 vs. J: 14.9 +/- 3.8), main curve location (A: 77 thoracic/23 lumbar, J: 76 thoracic/24 lumbar), main curve Cobb angle (A: 50.5 +/- 5.2 vs. J: 51.1 +/- 8.7), and thoracic kyphosis (A: 20.9 +/- 14.3 vs. J: 19.9 +/- 12.1) (P > 0.05, for all comparisons). Patients were evaluated using the first section of the SRS-24 which was divided into 4 domains: total pain, general self-image, general function, and activity. SRS-24 scores were statistical compared in individual domains and questions using the Mann-Whitney U test. American patients had significantly lower scores in pain (P < 0.0001, A: 3.7 +/- 0.8 vs. J: 4.3 +/- 0.4), function (P < 0.01, A: 3.9 +/- 0.6 vs. J: 4.2 +/- 0.5), and activity (P < 0.0001, A: 4.5 +/- 0.8 vs. J: 4.9 +/- 0.3) domains compared with Japanese patients. Japanese patients had significantly lower scores in the self-image (P < 0.0001, A: 4.0 +/- 0.7 vs. J: 3.5 +/- 0.5) domain. With regard to individual questions, there were significant differences in the scores between the 2 groups for all questions except 5 and 13 (P < 0.05, for all comparisons). SRS-24 scores in the Japanese idiopathic scoliosis population differed from that of the

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

PubMed

Kimura, Go; Ueda, Takeshi

2017-03-01

A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

Diagnosis and prevalence of protein-energy wasting and its association with mortality in Japanese haemodialysis patients.

PubMed

Kanazawa, Yoshie; Nakao, Toshiyuki; Murai, Seizo; Okada, Tomonari; Matsumoto, Hiroshi

2017-07-01

The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed the diagnostic criteria for protein-energy wasting (PEW). We studied Japanese haemodialysis (HD) patients to verify the diagnostic method, especially with respect to the body mass index (BMI) criterion, as well as the prevalence of PEW and its association with mortality. Japanese patients receiving maintenance HD at three outpatient clinics in Tokyo (n = 210) were enrolled, and prospectively followed-up for 3 years. PEW was diagnosed at baseline, according to the four categories (serum chemistry, body mass, muscle mass and dietary intake) recommended by the ISRNM. For the category of body mass, we select a body mass index (BMI) and set up three thresholds, <18.5, <20.0 and <23.0 kg/m 2 , as the diagnostic criterion. The patients who satisfied at least three out of the four categories were diagnosed as PEW. Protein-energy wasting, when the threshold of a BMI among the diagnostic criteria was defined as <18.5 kg/m 2 , was recognized as an independent risk factor for mortality. However, PEW was not recognized as a risk factor when the BMI diagnostic criterion was set at <20.0 or <23.0 kg/m 2 . Overall, 14.8% of the patients had PEW. The survival rate of PEW patients was significantly lower than that of non-PEW patients (log rank, P < 0.001). The diagnosis algorithm of PEW proposed by an expert panel of the ISRNM strongly associates with mortality. However, given differences in body size in Japan, we suggest to revise the BMI criterion from <23.0 kg/m 2 to <18.5 kg/m 2 . © 2016 Asian Pacific Society of Nephrology.

Markedly severe dystonia in Japanese encephalitis.

PubMed

Kalita, J; Misra, U K

2000-11-01

Encephalitis has been reported to be a rare cause of severe dystonia. We describe five patients with markedly severe dystonia from Japanese encephalitis. These patients with markedly severe dystonia were seen during the past 8 years as a subgroup of 50 patients with Japanese encephalitis. The diagnosis of markedly severe dystonia was based on increasingly frequent episodes of generalized dystonia with bulbar, respiratory, or metabolic derangement or leading to exhaustion or pain. The diagnosis of JE was based on clinicoradiologic features and a fourfold increase of hemagglutination-inhibiting antibody titers in paired serum. The outcome of the patients was defined as a good, partial, or poor recovery on the basis of 1-year clinical status. All the patients were males, and their ages ranged from 6 to 19 years. Movement disorders appeared 1 to 3 weeks after the illness as the level of consciousness started improving. During the next 1 to 4 weeks, patients began to experience markedly severe dystonia. It was associated with marked axial dystonia resulting in opisthotonus and retrocollis in five patients, jaw-opening dystonia in two patients, teeth clenching in one patient, and oculogyric crisis and neck deviation in another patient. The attacks of markedly severe dystonia lasted for 2 to 30 minutes and occurred as many as 20 to 30 times daily. Other developments included fixed limb dystonia in one patient, severe spasticity and rigidity in five patients, and focal muscle wasting in one patient. These patients had only a modest improvement after treatment. Markedly severe dystonia abated by 2 to 6 months in all the patients who were followed up. Cranial magnetic resonance imaging showed bilateral thalamic involvement in all patients, brainstem involvement in three patients, and basal ganglia involvement in two patients. At the 3-month follow-up, all patients had a poor outcome. At 1 year, one patient had a complete recovery; one had a partial recovery; and two were

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

PubMed

Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

2016-10-01

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Safety and effectiveness of long-term growth hormone therapy in Japanese patients with adult growth hormone deficiency: a postmarketing, multicenter, observational study.

PubMed

Shimatsu, Akira; Ishii, Hitoshi; Nishinaga, Hiromi; Murai, Osamu; Chihara, Kazuo

2017-07-28

We aimed to evaluate the long-term safety and effectiveness of growth hormone (GH) therapy in Japanese patients with adult growth hormone deficiency (AGHD). In this observational, multicenter study, Norditropin ® (Novo Nordisk A/S, Bagsvaerd, Denmark) was administered as injections of 0.021 mg/kg/week as a starting dose divided into 6-7 doses/week. The dose was increased according to clinical response. Patients' data were obtained from medical records. Measurements (lipids, glucose metabolism, and body composition) taken at baseline; 3, 6, and 12 months; and yearly until the end of the study were collected. Adverse drug reactions (ADRs), serious ADRs, and serious adverse events (SAEs) were evaluated. Of 387 registered patients, 334 were eligible for safety. After GH treatment initiation, a marked decrease in total cholesterol was observed earlier in the child-onset group than in the adult-onset group. LDL-cholesterol also decreased, but no significant differences in changes in LDL-cholesterol between adult-onset and child-onset groups were found. A significant increase in HDL-cholesterol starting 1 year after GH treatment initiation was found in the adult-onset group. There was no effect of GH treatment on glucose metabolism. Because of the small number of dual-energy X-ray absorptiometry data, the overall assessment of changes of body composition was difficult. Fifty-six (16.8%), 12 (3.6%), and 35 (10.5%) patients experienced ADRs, serious ADRs, and SAEs, respectively. This study demonstrated a favorable long-term safety and effectiveness profile of GH therapy in AGHD patients in the real-life Japanese clinical practice setting.

Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome.

PubMed

Abe, Ichiro; Sugimoto, Kaoru; Miyajima, Tetsumasa; Ide, Tomoko; Minezaki, Midori; Takeshita, Kaori; Takahara, Saori; Nakagawa, Midori; Fujimura, Yuki; Kudo, Tadachika; Miyajima, Shigero; Taira, Hiroshi; Ohe, Kenji; Ishii, Tatsu; Yanase, Toshihiko; Kobayashi, Kunihisa

2018-04-27

Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas. Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning ACTH level (<10 pg/mL) and a loss of the diurnal serum cortisol rhythm. Results Of the 61 patients, none (0%) had malignant tumors, 8 (13.1%) had pheochromocytoma, and 15 (24.6%) had primary aldosteronism; when diagnosed by our revised criteria, 13 (21.3%) had cortisol-secreting adenomas (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly lower rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index. Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

PubMed Central

Tanuma, Yasushi

2017-01-01

Objectives The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice. Methods A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined. Results The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years. Conclusions 35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment. Trial Registration This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910). PMID:28694823

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer

PubMed Central

WATANABE, JUNICHIRO; ITO, YOSHINORI; SAEKI, TOSHIAKI; MASUDA, NORIKAZU; TAKANO, TOSHIMI; TAKAO, SHINTARO; NAKAGAMI, KAZUHIKO; TSUGAWA, KOICHIRO; NAKAGAWA, SHINTARO; KANATANI, KAZUMITSU; NAKAYAMA, TAKAHIRO

2017-01-01

Background/Aim: Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab. Patients and Methods: Patients with inoperable or recurrent breast cancer who were previously treated with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were included. T-DM1 3.6 mg/kg was administered intravenously every 21 days. The administration dosage or schedule of T-DM1 was modified based on laboratory tests on the administration day. Results: Among 232 patients analyzed, adverse events were reported in 228 patients (98.3%); five patients (2.2%) discontinued due to adverse events and twenty patients (8.6%) had serious adverse events. The most commonly reported grade ≥3 adverse event of special interest was thrombocytopenia (69 patients; 29.7%), followed by hepatotoxicity (26 patients; 11.2%). Conclusion: T-DM1 was well tolerated in Japanese patients with HER2-positive advanced breast cancer and no new safety signals were observed. PMID:28438884

Resequencing and association analysis of OXTR with autism spectrum disorder in a Japanese population.

PubMed

Egawa, Jun; Watanabe, Yuichiro; Shibuya, Masako; Endo, Taro; Sugimoto, Atsunori; Igeta, Hirofumi; Nunokawa, Ayako; Inoue, Emiko; Someya, Toshiyuki

2015-03-01

The oxytocin receptor (OXTR) is implicated in the pathophysiology of autism spectrum disorder (ASD). A recent study found a rare non-synonymous OXTR gene variation, rs35062132 (R376G), associated with ASD in a Japanese population. In order to investigate the association between rare non-synonymous OXTR variations and ASD, we resequenced OXTR and performed association analysis with ASD in a Japanese population. We resequenced the OXTR coding region in 213 ASD patients. Rare non-synonymous OXTR variations detected by resequencing were genotyped in 213 patients and 667 controls. We detected three rare non-synonymous variations: rs35062132 (R376G/C), rs151257822 (G334D), and g.8809426G>T (R150S). However, there was no significant association between these rare non-synonymous variations and ASD. Our present study does not support the contribution of rare non-synonymous OXTR variations to ASD susceptibility in the Japanese population. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Safety, Effectiveness, and Treatment Persistence of Golimumab in Elderly Patients with Rheumatoid Arthritis in Real-World Clinical Practice in Japan.

PubMed

Okazaki, Masateru; Kobayashi, Hisanori; Shimizu, Hirohito; Ishii, Yutaka; Yajima, Tsutomu; Kanbori, Masayoshi

2018-06-01

Golimumab has been proven as an effective treatment for rheumatoid arthritis in clinical trials. However, there is a scarcity of data regarding its use in elderly patients in a real-world setting. This study aims to evaluate the safety, effectiveness, and treatment persistence of golimumab in elderly Japanese patients (≥ 75 years) with rheumatoid arthritis. This study was a post hoc analysis of post-marketing surveillance data on 5137 Japanese patients with active rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided into two age groups (younger: < 75 years and elderly: ≥ 75 years), and the safety, effectiveness, and treatment persistence of golimumab were assessed. Also, the reasons for discontinuing golimumab treatment were analyzed by multi-logistic regression. During golimumab treatment over 24 weeks, younger and elderly groups exhibited comparable improvement of disease activity as measured by EULAR response criteria with similar overall rates of adverse events. However, the survival curve of golimumab for elderly patients was significantly different from that for younger patients due largely to the discontinuation at 4 weeks. The most common reason for discontinuation in elderly patients was patient choice, while it was disease progression in younger patients. Analysis of elderly patients who discontinued treatment by their own decision identified EULAR good response as a factor associated with continuation of golimumab treatment whereas no predictive factor associated with discontinuation was identified. The safety and effectiveness of golimumab treatment in elderly Japanese patients aged 75 years or older were comparable to those in younger patients in real-world clinical practice. Analysis of the survival curves suggested that continuous use of golimumab might further improve clinical benefit of golimumab in elderly patients, underpinning the importance of effective communication between physicians and

Earthquake Preparedness Among Japanese Hemodialysis Patients in Prefectures Heavily Damaged by the 2011 Great East Japan Earthquake.

PubMed

Sugisawa, Hidehiro; Shimizu, Yumiko; Kumagai, Tamaki; Sugisaki, Hiroaki; Ohira, Seiji; Shinoda, Toshio

2017-08-01

The purpose of this study was to explore the factors related to earthquake preparedness in Japanese hemodialysis patients. We focused on three aspects of the related factors: health condition factors, social factors, and the experience of disasters. A mail survey of all the members of the Japan Association of Kidney Disease Patients in three Japanese prefectures (N = 4085) was conducted in March, 2013. We obtained 1841 valid responses for analysis. The health factors covered were: activities of daily living (ADL), mental distress, primary renal diseases, and the duration of dialysis. The social factors were: socioeconomic status, family structure, informational social support, and the provision of information regarding earthquake preparedness from dialysis facilities. The results show that the average percentage of participants that had met each criterion of earthquake preparedness in 2013 was 53%. Hemodialysis patients without disabled ADL, without mental distress, and requiring longer periods of dialysis, were likely to meet more of the earthquake preparedness criteria. Hemodialysis patients who had received informational social support from family or friends, had lived with spouse and children in comparison to living alone, and had obtained information regarding earthquake preparedness from dialysis facilities, were also likely to meet more of the earthquake preparedness criteria. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Prognostic models for renal cell carcinoma recurrence: external validation in a Japanese population.

PubMed

Utsumi, Takanobu; Ueda, Takeshi; Fukasawa, Satoshi; Komaru, Atsushi; Sazuka, Tomokazu; Kawamura, Koji; Imamoto, Takashi; Nihei, Naoki; Suzuki, Hiroyoshi; Ichikawa, Tomohiko

2011-09-01

The aim of the present study was to compare the accuracy of three prognostic models in predicting recurrence-free survival among Japanese patients who underwent nephrectomy for non-metastatic renal cell carcinoma (RCC). Patients originated from two centers: Chiba University Hospital (n = 152) and Chiba Cancer Center (n = 65). The following data were collected: age, sex, clinical presentation, Eastern Cooperative Oncology Group performance status, surgical technique, 1997 tumor-node-metastasis stage, clinical and pathological tumor size, histological subtype, disease recurrence, and progression. Three western models, including Yaycioglu's model, Cindolo's model and Kattan's nomogram, were used to predict recurrence-free survival. Predictive accuracy of these models were validated by using Harrell's concordance-index. Concordance-indexes were 0.795 and 0.745 for Kattan's nomogram, 0.700 and 0.634 for Yaycioglu's model, and 0.700 and 0.634 for Cindolo's model, respectively. Furthermore, the constructed calibration plots of Kattan's nomogram overestimated the predicted probability of recurrence-free survival after 5 years compared with the actual probability. Our findings suggest that despite working better than other predictive tools, Kattan's nomogram needs be used with caution when applied to Japanese patients who have undergone nephrectomy for non-metastatic RCC. © 2011 The Japanese Urological Association.

Detailed analysis of the supermarket task included on the Japanese version of the Rapid Dementia Screening Test.

PubMed

Moriyama, Yasushi; Yoshino, Aihide; Muramatsu, Taro; Mimura, Masaru

2017-05-01

The supermarket task, which is included in the Japanese version of the Rapid Dementia Screening Test, requires the quick (1 min) generation of words for things that can be bought in a supermarket. Cluster size and switches are investigated during this task. We investigated how the severity of dementia related to cluster size and switches on the supermarket task in patients with Alzheimer's disease. We administered the Japanese version of the Rapid Dementia Screening Test to 250 patients with very mild to severe Alzheimer's disease and to 49 healthy volunteers. Patients had Mini-Mental State Examination scores from 12 to 26 and Clinical Dementia Rating scale scores from 0.5 to 3. Patients were divided into four groups based on their Clinical Dementia Rating score (0.5, 1, 2, 3). We performed statistical analyses between the four groups and control subjects based on cluster size and switch scores on the supermarket task. The score for cluster size and switches deteriorated according to the severity of dementia. Moreover, for subjects with a Clinical Dementia Rating score of 0.5, cluster size was impaired, but switches were intact. Our findings indicate that the scores for cluster size and switches on the supermarket task may be useful for detecting the severity of symptoms of dementia in patients with Alzheimer's disease. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

PubMed Central

Torisu, Yuichi; Nakano, Masanori; Takano, Keiko; Nakagawa, Ryo; Saeki, Chisato; Hokari, Atsushi; Ishikawa, Tomohisa; Saruta, Masayuki; Zeniya, Mikio

2017-01-01

AIM To evaluate the therapeutic effects of ursodeoxycholic acid (UDCA) on autoimmune hepatitis (AIH). METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy (Group U, n = 48) and prednisolone (PSL) monotherapy (Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse (Subgroup U1, n = 34) and patients who additionally received PSL during follow-up (Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factors contributing to the response to UDCA monotherapy. RESULTS In Group U, 34 patients (71%) achieved and maintained remission over 49 (range: 8-90) mo (Subgroup U1) and 14 patients (29%) additionally received PSL (Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse (15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7 (range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase (ALT) levels at onset (124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation (A1) on histological examination (70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference (P = 0.013). CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Contemporary issues concerning informed consent in Japan based on a review of court decisions and characteristics of Japanese culture.

PubMed

Masaki, Sakiko; Ishimoto, Hiroko; Asai, Atsushi

2014-02-04

Since Japan adopted the concept of informed consent from the West, its inappropriate acquisition from patients in the Japanese clinical setting has continued, due in part to cultural aspects. Here, we discuss the current status of and contemporary issues surrounding informed consent in Japan, and how these are influenced by Japanese culture. Current legal norms towards informed consent and information disclosure are obscure in Japan. For instance, physicians in Japan do not have a legal duty to inform patients of a cancer diagnosis. To gain a better understanding of these issues, we present five court decisions related to informed consent and information disclosure. We then discuss Japanese culture through reviews of published opinions and commentaries regarding how culture affects decision making and obtaining informed consent. We focus on two contemporary problems involving informed consent and relevant issues in clinical settings: the misuse of informed consent and persistence in obtaining consent. For the former issue, the phrase "informed consent" is often used to express an opportunity to disclose medical conditions and recommended treatment choices. The casual use of the expression "informed consent" likely reflects deep-rooted cultural influences. For the latter issue, physicians may try to obtain a signature by doing whatever it takes, lacking a deep understanding of important ethical principles, such as protecting human dignity, serving the patient's best interest, and doing no harm in decision-making for patients.There is clearly a misunderstanding of the concept of informed consent and a lack of complete understanding of ethical principles among Japanese healthcare professionals. Although similar in some respects to informed consent as it originated in the United States, our review makes it clear that informed consent in Japan has clear distinguishing features. Japanese healthcare professionals should aim to understand the basic nature of informed

A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

PubMed

Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

2015-03-01

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

Phase II trial of capecitabine plus modified cisplatin (mXP) as first-line therapy in Japanese patients with metastatic gastric cancer (KSCC1104).

PubMed

Satake, Hironaga; Iwatsuki, Masaaki; Uenosono, Yoshikazu; Shiraishi, Takeshi; Tanioka, Hiroaki; Saeki, Hiroshi; Sugimachi, Keishi; Kitagawa, Dai; Shimokawa, Mototsugu; Oki, Eiji; Emi, Yasunori; Kakeji, Yoshihiro; Tsuji, Akihito; Akagi, Yoshito; Natsugoe, Shoji; Baba, Hideo; Maehara, Yoshihiko

2017-01-01

Capecitabine plus cisplatin (XP) is a standard therapy for metastatic gastric cancer (mGC). However, while results from previous phase III trials suggested that the cisplatin dosage should be reduced in Japanese patients, no clinical data exist to support this. Here, we conducted a multicenter study to evaluate the efficacy and safety of modified XP (mXP) in Japanese patients with mGC. Patients with previously untreated mGC received mXP (cisplatin 60 mg/m 2 on day 1 plus capecitabine 1000 mg/m 2 twice daily on days 1-14) every 3 weeks. The primary endpoint was the Response Evaluation Criteria in Solid Tumors-confirmed overall response rate (ORR). A sample size of 40 was planned for a threshold ORR of 30% and an expected value of 50%, with a one-sided α of 0.05 and a beta of approximately 0.2. Forty-two patients were enrolled. One patient did not fulfill the eligibility criteria; therefore, a total of 41 patients were assessed. The results were as follows: complete response in 2 patients, partial response in 16, stable disease in 14, progressive disease in 8, and no evaluation in 1. The confirmed ORR was 43.9% (95% confidence interval 28.7-59.1%). The median progression-free survival and median overall survival were 4.6 and 11.3 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (37.5%), anemia (24.4%), anorexia (24.4%), and nausea (12.2%). First-line chemotherapy with mXP in Japanese patients with mGC did not reach its primary objective. However, it did show a promising response rate and an acceptable tolerability profile.

[Correlation between the SF-8 health status questionnaire and JRQLQ in patients with Japanese cedar pollinosis].

PubMed

Fujii, Tsukasa; Ogino, Satoshi; Arimoto, Hiroe; Irifune, Morihiro; Iwata, Nobuko; Ookawachi, Ichiro; Kikumori, Hiroshi; Seo, Ritsu; Takeda, Mariko; Tamaki, Akiko; Baba, Kenji; Nose, Michihiro

2007-02-01

It is reported that the health-related quality of life (HRQL) is an important outcome in the Japanese Cedar Pollinosis (JCP) treatment. In Japan, the disease-specific Japan Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) and the generic SF-36 Health Survey (SF-36) has been used. The aim of this study is to investigate more profitable QOL by using both the disease-specific questionnaire and the non-disease-specific questionnaire together. 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) in 2005 were questioned, and 240 patients were engaged in this study as subjects. In this study, the QOL scores were evaluated using the JRQLQ and SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. Using factor analysis and the correlation matrix, we showed that the disease-specific and the general health instrument covered a different half the total measurable HRQL. There was some correlation between the SF-8 items with the JRQLQ domains. There was little correlation between the SF-8 items and symptom scores, while, there was high correlation between the JRQLQ and symptom scores. The "Usual daily activities" domain in the JRQLQ correlated with any rhinoconjunctivitis symptoms. Both JRQLQ and SF-8 can be used to assess the quality of life of patients with JCP. Each instrument measures the aspects of the HRQL that hardly overlaps. For an assessment of the HRQL in JCP that is complete and responsive both instruments should be employed together.

Lower urinary tract symptoms and erectile dysfunction associated with depression among Japanese patients with late-onset hypogonadism symptoms.

PubMed

Takao, Tetsuya; Tsujimura, Akira; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Nonomura, Norio; Okuyama, Akihiko

2011-06-01

The aim of this study was to investigate the relation between lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and depression in Japanese patients with late-onset hypogonadism (LOH) symptoms. The study comprised 87 Japanese patients with LOH symptoms (>27 points on the Aging Males Symptoms Scale). Thirty-four patients were diagnosed as having depression and the remaining 53 patients were diagnosed as not having depression by the Mini International Neuropsychiatric Interview. We compared the International Index of Erectile Function (IIEF) 5, International Prostate Symptom Score (IPSS), IPSS quality-of-life (QOL) index, King's Health Questionnaire (KHQ), endocrinological data, and free uroflow study between depression and non-depression patients and performed multiple logistic regression analysis. IIEF5 scores of depression patients were significantly lower than those of non-depression patients. In KHQ, only the category of general health perceptions was significantly higher in depression patients than non-depression patients. However, IPSS, QOL index, and endocrinological and uroflowmetric data showed no significant difference between the groups. Multiple logistic regression analysis revealed moderate and severe ED to be risk factors for depression. However, LUTS are not related to depression. Moderate and severe ED is correlated with depression, whereas LUTS are not related to depression in Japanese LOH patients.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder.

PubMed

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder

PubMed Central

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered. PMID:22934180

Impact of diabetes mellitus on outcomes in Japanese patients undergoing coronary artery bypass grafting.

PubMed

Minakata, Kenji; Bando, Ko; Takanashi, Shuichiro; Konishi, Hiroaki; Miyamoto, Yoshihiro; Ueshima, Kenji; Sato, Tosiya; Ueda, Yuichi; Okita, Yutaka; Masuda, Izuru; Okabayashi, Hitoshi; Yaku, Hitoshi; Yasuno, Shinji; Muranaka, Hiroyuki; Kasahara, Masato; Miyata, Shigeki; Okamura, Yoshitaka; Nasu, Michihiro; Tanemoto, Kazuo; Arinaga, Koichi; Hisashi, Yosuke; Sakata, Ryuzo

2012-05-01

There have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG). A multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality. There were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001). Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG) were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl, and 136mg/dl in the non-DM group (all p<0.0001). Although there were no significant differences in postoperative cardiovascular events, the incidence of infection was significantly higher in the DM group than in the non-DM group (9.2% vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%, p=0.12), and this was likely related to infection. DM patients had worse perioperative BG control, higher incidence of infection, and higher mortality than non-DM patients. These results indicate that perioperative BG control guidelines should be standardized to obtain better surgical outcomes in Japanese DM patients. Copyright © 2012. Published by Elsevier Ltd.

[Questionnaire on suitableness and acceptableness of cancer notification in aged Japanese prostate cancer patients].

PubMed

Noguchi, Kazumi; Uemura, Hiroji; Teranishi, Jun-ichi; Fujinami, Kiyoshi; Miyoshi, Yasuhide; Nakaigawa, Noboru; Saito, Kazuo; Kubota, Yoshinobu

2006-01-01

In Japan, sometimes a patient with malignant fatal disease is not informed the diagnosis. We tried to investigate if the informed consent of cancer notification is acceptable and suitable for aged Japanese prostate cancer patients. From January to June 2003, we distributed a questionnaire to outpatients who had been followed up for more than 6 months after the diagnosis of prostate cancer. These patients declared a wish to be notified the true diagnosis in their first visit to our department and were informed that they had prostate cancer just after the diagnosis. Ninety-one per cent of patients (54 patients, mean age was 74.8 +/- 6.1 years old) answered to our questionnaire. Clinical stage consisted of 14 cases of B1, 13 cases of B2, 15 cases of C, 3 cases of D1, and 9 cases of D2. The histopathological grade consisted of 6 cases of well differentiated carcinoma, 32 cases of moderately differentiated carcinoma, and 16 cases of poorly differentiated carcinoma. Eleven cases underwent total prostatectomy (B1 and B2) and 44 cases had androgen deprivation therapy. Seventy-six per cent of patients understood and accepted their illness within a few days. However, 11% of patients took more than 3 months to accept their malignant disease. They answered that they could accept their illness given with a relationship of mutual trust between themselves as patients and the medical staff, effective medical treatment, and with the help of their family. They also answered that the most important emotional support was given by their wives (46.3%) and doctors (27.8%). In the early days following the diagnosis, they worried about their remaining days, the risks or side effects of the treatment, their family, and their job. Several months following the diagnosis, they were concerned about recurrence of the disease, their family, medical expenses, and their old age. Those who did not worry at all doubled from 11.1% immediately after the diagnosis to 22.2% several months later. More

Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

PubMed

Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

2017-08-01

Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

Analysis of Early Death in Japanese Patients With Advanced Non-small-cell Lung Cancer Treated With Nivolumab.

PubMed

Inoue, Takako; Tamiya, Motohiro; Tamiya, Akihiro; Nakahama, Kenji; Taniguchi, Yoshihiko; Shiroyama, Takayuki; Isa, Shin-Ichi; Nishino, Kazumi; Kumagai, Toru; Kunimasa, Kei; Kimura, Madoka; Suzuki, Hidekazu; Hirashima, Tomonori; Atagi, Shinji; Imamura, Fumio

2018-03-01

The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting. The medical records of patients with NSCLC who started receiving nivolumab between December 17, 2015 and July 31, 2016 in 3 Japanese institutes were collected. Early death was defined as any death within 3 months from the start of nivolumab treatment, irrespective of its cause. Treatment response was evaluated using the Response Evaluation Criteria In Solid Tumors criteria, version 1.1. A total of 201 patients with NSCLC were enrolled, and 38 (18.9%) died within the first 3 months. Thirty-one (81.6%) patients who experienced early death developed progressive disease, whereas 14 (36.8%) patients who experienced early death demonstrated nivolumab-induced immune-related adverse events, which required corticosteroid intervention, including interstitial lung disease in 7 (18.4%) patients. Multivariate logistic regression demonstrated that an Eastern Cooperative Oncology Group performance status score ≥ 2 (odds ratio [OR], 5.66; 95% confidence interval [CI], 2.01-15.61; P < .001), C-reactive protein-to-albumin ratio > 0.3 (OR, 10.56; 95% CI, 3.61-30.86; P < .001), and the response to prior treatment (OR, 2.07; 95% CI, 1.03-4.14; P = .041) were independent predictors for early death. Disease progression and immune-related adverse events are 2 major causes of early death with nivolumab in patients with NSCLC. An Eastern Cooperative Oncology Group performance status score ≥ 2, pretreatment C-reactive protein-to-albumin ratio > 0.3, and poor response to prior treatment were associated with early death. Copyright © 2017 Elsevier Inc. All rights reserved.

Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature.

PubMed

Takamura, Saori; Teraki, Yuichi

2016-04-01

Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder-associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder-associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation-related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy-related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation-related EPF occurred on the face and trunk of young and middle-aged men and women, whereas hematological malignancy-related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation-related EPF. These observations suggest variations among patients with EPF associated with hematological disorders. © 2015 Japanese Dermatological Association.

Clinical characteristics of pneumonia in bedridden patients receiving home care: a 3-year prospective observational study.

PubMed

Ishida, Tadashi; Tachibana, Hiromasa; Ito, Akihiro; Ikeda, Satoshi; Furuta, Kenjiro; Nishiyama, Akihiro; Noyama, Maki; Tokioka, Fumiaki; Yoshioka, Hiroshige; Arita, Machiko

2015-08-01

The aim of the study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of bedridden pneumonia patients receiving home healthcare. A 3-year prospective observational study of poor performance status (PS) 3-4 patients receiving long-term home healthcare and hospitalized at a single center with pneumonia between October 2010 and September 2013 was conducted, and their clinical characteristics were compared with non-bedridden community-acquired pneumonia (CAP) patients. A total of 131 CAP patients with PS 3-4, and 400 CAP patients with PS 0-2 were evaluated. The PS 3-4 patients were older, and exhibited a higher frequency of underlying diseases. Aspiration was thought to be associated with pneumonia in 77.1% of the PS 3-4 patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of streptococci and polymicrobial infections was higher in the PS 3-4 group. The incidence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa was lower than in previous healthcare-associated pneumonia reports. The in-hospital mortality and recurrence rates were significantly higher in the PS 3-4 group than in the good PS group (17.6% vs. 6.0%, p < 0.001 and 15.3% vs. 7.5%, p = 0.008, respectively). The clinical characteristics of pneumonia in poor PS patients were similar to healthcare-associated pneumonia (HCAP), except for the frequency of drug-resistant pathogens. Hence, it might be beneficial to categorize pneumonia in home residents with poor PS separately from pneumonia in CAP patients who were previously healthy or experienced mild comorbidities. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Negotiating end-of-life decision making: a comparison of Japanese and U.S. residents' approaches.

PubMed

Gabbay, Baback B; Matsumura, Shinji; Etzioni, Shiri; Asch, Steven M; Rosenfeld, Kenneth E; Shiojiri, Toshiaki; Balingit, Peter P; Lorenz, Karl A

2005-07-01

To compare Japanese and U.S. resident physicians' attitudes, clinical experiences, and emotional responses regarding making disclosures to patients facing incurable illnesses. From September 2003 to June 2004, the authors used a ten-item self-administered anonymous questionnaire in a cross-sectional survey of 103 internal medicine residents at two U.S. sites in Los Angeles, California, and 244 general medical practice residents at five Japanese sites in Central Honshu, Kyushu, Okinawa, Japan. The Japanese residents were more likely to favor including the family in disclosing diagnosis (95% versus 45%, p<.001) and prognosis (95% versus 51%, p<.001) of metastatic gastric cancer. Of residents who favored diagnostic or prognostic disclosure to both the patient and family, Japanese residents were more likely to prefer discussion with the family first. Trainees in Japan expressed greater uncertainty about ethical practices related to disclosure of diagnosis or prognosis. Many Japanese and U.S. residents indicated that they had deceived a patient at the request of a family (76% versus 18 %, p<.001), or provided nonbeneficial care (56% versus 72%, p<.05), and many expressed guilt about these behaviors. The residents' approaches to end-of-life decision making reflect known cultural preferences related to the role of patients and their families. Although Japanese trainees were more likely to endorse the role of the family, they expressed greater uncertainty about their approach. Difficulty and uncertainty in end-of-life decision making were common among both the Japanese and U.S. residents. Both groups would benefit from ethical training to negotiate diverse, changing norms regarding end-of-life decision making.

Contemporary issues concerning informed consent in Japan based on a review of court decisions and characteristics of Japanese culture

PubMed Central

2014-01-01

Background Since Japan adopted the concept of informed consent from the West, its inappropriate acquisition from patients in the Japanese clinical setting has continued, due in part to cultural aspects. Here, we discuss the current status of and contemporary issues surrounding informed consent in Japan, and how these are influenced by Japanese culture. Discussion Current legal norms towards informed consent and information disclosure are obscure in Japan. For instance, physicians in Japan do not have a legal duty to inform patients of a cancer diagnosis. To gain a better understanding of these issues, we present five court decisions related to informed consent and information disclosure. We then discuss Japanese culture through reviews of published opinions and commentaries regarding how culture affects decision making and obtaining informed consent. We focus on two contemporary problems involving informed consent and relevant issues in clinical settings: the misuse of informed consent and persistence in obtaining consent. For the former issue, the phrase "informed consent" is often used to express an opportunity to disclose medical conditions and recommended treatment choices. The casual use of the expression "informed consent" likely reflects deep-rooted cultural influences. For the latter issue, physicians may try to obtain a signature by doing whatever it takes, lacking a deep understanding of important ethical principles, such as protecting human dignity, serving the patient’s best interest, and doing no harm in decision-making for patients. There is clearly a misunderstanding of the concept of informed consent and a lack of complete understanding of ethical principles among Japanese healthcare professionals. Although similar in some respects to informed consent as it originated in the United States, our review makes it clear that informed consent in Japan has clear distinguishing features. Summary Japanese healthcare professionals should aim to understand

Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

ERIC Educational Resources Information Center

Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

2016-01-01

The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

PubMed Central

Satoh, Jo; Kohara, Nobuo; Sekiguchi, Kenji; Yamaguchi, Yasuyuki

2016-01-01

We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID:26881251

Relationship between airborne pollen count and treatment outcome in Japanese cedar pollinosis patients.

PubMed

Takasaki, Kenji; Enatsu, Kaori; Kumagami, Hidetaka; Takahashi, Haruo

2009-05-01

In Japan, information on daily Japanese cedar pollen counts is made public during pollen season. If symptom severity and treatment outcome are predictable according to these pollen counts, management of seasonal allergic rhinitis may become more precise. The aims of the study were to evaluate the relationship between airborne pollen counts, symptom severity and treatment outcome in Japanese cedar pollinosis patients. In the randomized study, patients with moderate to most severe Japanese pollinosis were treated with fexofenadine (60 mg BD) or fexofenadine and nasal corticosteroids for 2 weeks. During the same period daily airborne pollen counts were measured. A total of 105 adult patients were enrolled. No difference of treatment efficacy was seen among groups. Detailed results of efficacy and safety were previously described elsewhere. In univariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study tended to affect symptom severity (P = 0.053) and the mean cumulative amount of airborne pollen during the treatment period tended to show difference among five treatment outcome categories (P = 0.066). In multivariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study was identified as the only significant factor of symptom severity (P = 0.0327) and cumulative amount of airborne pollen during the treatment period (P = 0.027) and allergic history (P = 0.027) were significant factors of treatment outcomes. No serious adverse effect was reported during the study. The amount of airborne pollen may be predictive of both symptom severity and treatment outcome.

Dimensional analyses of frontal posed smile attractiveness in Japanese female patients.

PubMed

Hata, Kyoko; Arai, Kazuhito

2016-01-01

To identify appropriate dimensional items in objective diagnostic analysis for attractiveness of frontal posed smile in Japanese female patients by comparing with the result of human judgments. Photographs of frontal posed smiles of 100 Japanese females after orthodontic treatment were evaluated by 20 dental students (10 males and 10 females) using a visual analogue scale (VAS). The photographs were ranked based on the VAS evaluations and the 25 photographs with the highest evaluations were selected as group A, and the 25 photos with the lowest evaluations were designated group B. Then 12 dimensional items of objective analysis selected from a literature review were measured. Means and standard deviations for measurements of the dimensional items were compared between the groups using the unpaired t-test with a significance level of P < .05. Mean values were significantly smaller in group A than in group B for interlabial gap, intervermilion distance, maxillary gingival display, maximum incisor exposure, and lower lip to incisor (P < .05). Significant differences were observed only in the vertical dimension, not in the transverse dimension. Five of the 12 objective diagnostic items were correlated with human judgments of the attractiveness of frontal posed smile in Japanese females after orthodontic treatment.

A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

PubMed Central

AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

2014-01-01

Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

Rubbing skin with nylon towels as a major cause of pseudomonas folliculitis in a Japanese population.

PubMed

Teraki, Yuichi; Nakamura, Kaori

2015-01-01

Pseudomonas folliculitis (PF) is a community-acquired skin infection, which develops after exposure to contaminated water such as whirlpools, swimming pools, water slides and hot tubs. In Japan, this condition has been sporadically reported, often in association with bathing; however, the exact cause of PF in the Japanese population remains unclear. In this study, we retrospectively reviewed 10 patients with PF diagnosed at our dermatology clinic (two males and eight females). Four patients had recurrences over 1-3 years. Notably, eight of the 10 patients were rubbing their bodies with nylon towels or sponges placed in the bathrooms during bathing. Pseudomonas aeruginosa was isolated from the nylon towels used in two of the two patients examined. Discontinued use of nylon towels resulted in prompt resolution of PF and no recurrence in all cases. Our observation suggests that rubbing the skin with nylon towels contaminated with P. aeruginosa was a major cause of PF in a Japanese population. © 2014 Japanese Dermatological Association.

Fulminant type 1 diabetes mellitus in Japanese children and adolescents: multi-institutional joint research of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes.

PubMed

Shiga, Kentaro; Urakami, Tatsuhiko; Suzuki, Junichi; Igarashi, Yasuhiro; Tajima, Hanako; Amemiya, Shin; Sugihara, Shigetaka

2018-05-22

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu-like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics.

The once-daily human glucagon-like peptide-1 analog, liraglutide, improves β-cell function in Japanese patients with type 2 diabetes.

PubMed

Seino, Yutaka; Rasmussen, Mads Frederik; Clauson, Per; Kaku, Kohei

2012-08-20

Aims/Introduction:  β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-B) index, proinsulin:insulin and proinsulin:C-peptide ratios in adult, Japanese type 2 diabetes patients receiving liraglutide.   Data from two randomized, controlled clinical trials (A and B) including 664 Japanese type 2 diabetes patients (mean values: glycated hemoglobin [HbA1c] 8.61-9.32%; body mass index [BMI] 24.4-25.3 kg/m(2)) were analyzed. In two 24-week trials, patients received liraglutide 0.9 mg (n = 268) or glibenclamide 2.5 mg (n = 132; trial A), or liraglutide 0.6, 0.9 mg (n = 176) or placebo (n = 88) added to previous sulfonylurea therapy (trial B).   Liraglutide was associated with improved glycemic control vs sulfonylurea monotherapy or placebo. In liraglutide-treated groups in trials A and B, area under the curve (AUC) insulin 0-3 h was improved (P < 0.001 for all) and the AUCinsulin 0-3 h:AUCglucose 0-3 h ratio was increased (estimated treatment difference [liraglutide-comparator] 0.058 [0.036, 0.079]). HOMA-B significantly increased with liraglutide relative to comparator in trial B (P < 0.05), but not in trial A. The reduction in fasting proinsulin:insulin ratio was 50% greater than in comparator groups.   In Japanese type 2 diabetes patients, liraglutide was associated with effective glycemic control, restoration of prandial insulin response and indications of improved β-cell function. This trial was registered with Clinicaltrials.gov (trial A: no. NCT00393718/JapicCTI-060328 and trial B: no. NCT00395746/JapicCTI-060324). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00193.x, 2012).

Relations of nutritional intake to age, sex and body mass index in Japanese elderly patients with type 2 diabetes: the Japanese Elderly Diabetes Intervention Trial.

PubMed

Yoshimura, Yukio; Kamada, Chiemi; Takahashi, Keiko; Kaimoto, Tae; Iimuro, Satoshi; Ohashi, Yasuo; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Ito, Hideki

2012-04-01

To determine the status of nutritional intake in elderly Japanese patients with type 2 diabetes aged 65 years or older, and to clarify relations of nutritional intake to age, sex and body mass index (BMI). Clinical parameters and nutritional intake were investigated and compared in 912 (417 men, 495 women) elderly Japanese patients with type 2 diabetes registered to the Japanese Elderly Diabetes Intervention Trial. The mean daily energy intake of patients was 1802 kcal in men and 1661 kcal in women, respectively. The energy intakes per kilogram of standard bodyweight in both sexes and the energy intakes per kilogram of present bodyweight in men increased significantly with age. The protein : fat : carbohydrate (PFC) energy ratio (%E) was 15.2:25.4:59.5 in men, and 15.7:25.8:58.6 in women, respectively. Grain, oil, alcohol and soft drink intakes were higher in men than in women. Potato, fruit and green vegetable intakes were higher in women than in men. Fruit intake showed a significant age-related increase in men. In women, there was an age-related significant decrease of meat intake. An increase of BMI correlated with a significant increase in bodyweight, waist circumference, hip circumference, waist-to-hip ratio, triglycerides and diastolic blood pressure. The mean energy intake of three BMI groups, lean (BMI < 18.5 kg/m(2)), normal (18.5 kg/m(2)

[Comparison of dissolution profile and plasma concentration-time profile of the thalidomide formulations made by Japanese, Mexican and British companies].

PubMed

Fujita, Yukiyoshi; Yamamoto, Koujirou; Aomori, Tohru; Murakami, Hirokazu; Horiuchi, Ryuya

2008-10-01

Thalidomide is an important advance in the treatment of multiple myeloma. In Japan thalidomide is now on the approval step for the treatment of multiple myeloma. The drug has some bothersome side effects such as defect of organogenesis, neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy and is changing multiple myeloma treatment. At this moment, Japanese patients must import the thalidomide preparations from Mexico, Britain and elsewhere, but after approval, they patients will be able to get the new Japanese thalidomide capsules. In order to determine appropriate amounts of Japanese thalidomide capsules in the treatment of multiple myeloma, we compared the dissolution profile and plasma thalidomide concentrations of Japanese and British capsules and Mexican tablets. The dissolution test was performed according to the Japanese and the United States Pharmacopoeia. The pharmacokinetic data for Japanese capsules were obtained from the clinical trial in Japanese subjects and compared with those data published for other formulations. The dissolution rate of the Japanese capsule was the fastest, followed by British and Mexican formulations. The pharmacokinetic profiles of Japanese and British capsules were similar, while the 100 mg Japanese thalidomide capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200 mg Mexican thalidomide tablet (1.7 vs. 1.1 microg/ml), greatly shortened t(max) (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic absorption profiles demonstrated a rank-order correlation. Physicians and pharmacists should be aware of the probable alteration in plasma thalidomide concentration when switching to the Japanese capsule, especially from the Mexican tablet, and should monitor clinical response carefully.

Real-world cardiovascular assessment of mirabegron treatment in patients with overactive bladder and concomitant cardiovascular disease: Results of a Japanese post-marketing study.

PubMed

Katoh, Takao; Kuwamoto, Kana; Kato, Daisuke; Kuroishi, Kentarou

2016-12-01

To assess the effect of 25 or 50 mg mirabegron on cardiovascular end-points and adverse drug reactions in real-world Japanese patients with overactive bladder and cardiovascular disease. Participants had overactive bladder, a history of/coexisting cardiovascular disease and a 12-lead electrocardiogram carried out ≤7 days before initiating 4 weeks of mirabegron treatment. Patients with "serious cardiovascular disease" (class III or IV on the New York Heart Association functional classification and further confirmed by expert analysis) were excluded. Patient demographics, physical characteristics and cardiovascular history were recorded. After 4 weeks, patients underwent another electrocardiogram. Incidence of cardiovascular adverse drug reactions and change from baseline in electrocardiogram parameters (RR, PR, QRS intervals, Fridericia's corrected QT and heart rate) were assessed. Of 316 patients registered, 236 met criteria and had baseline/post-dose electrocardiograms: 61.9% male; 60.2% aged ≥75 years; 93.6% with coexisting cardiovascular disease, notably, arrhythmia (67.8%) and angina pectoris (19.1%). Starting mirabegron daily doses were 25 mg (19.9%) or 50 mg (80.1%). The incidence of cardiovascular adverse drug reactions was 5.51%. After 4 weeks, the mean heart rate increased by 1.24 b.p.m. (statistically significant, but clinically acceptable as per previous trials). No significant changes were observed in PR, QRS or Fridericia's corrected QT. No significant correlations in the total population or age-/sex-segregated subgroups were observed between baseline Fridericia's corrected QT and change at 4 weeks. No correlation for heart rate versus change from baseline heart rate with treatment was observed. Mirabegron was well tolerated in real-world Japanese patients with overactive bladder and coexisting cardiovascular disease. No unexpected cardiovascular safety concerns were observed. © 2016 The Japanese Urological Association.

The EXPAND study: Efficacy and safety of rivaroxaban in Japanese patients with non-valvular atrial fibrillation.

PubMed

Shimokawa, Hiroaki; Yamashita, Takeshi; Uchiyama, Shinichiro; Kitazono, Takanari; Shimizu, Wataru; Ikeda, Takanori; Kamouchi, Masahiro; Kaikita, Koichi; Fukuda, Koji; Origasa, Hideki; Sakuma, Ichiro; Saku, Keijiro; Okumura, Yasuo; Nakamura, Yuichiro; Morimoto, Hideo; Matsumoto, Naoki; Tsuchida, Akihito; Ako, Junya; Sugishita, Nobuyoshi; Shimizu, Shogo; Atarashi, Hirotsugu; Inoue, Hiroshi

2018-05-01

The EXPAND study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients ≥20 years of age (mean, 71.6 ± 9.4 years) who were being or about to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for an average of 897.1 (±206.8) days with a high follow-up rate (99.65%). The mean CHADS 2 score at baseline was 2.1 (1.3) (0-1, 37%; 2, 29%; ≥3, 34%). The total incidence rate of symptomatic stroke and SE (primary efficacy endpoint) was 1.0%/year, and 0.5%, 0.9%, and 1.7%/year for those with CHADS 2 scores of 0-1, 2, and ≥3, respectively. Cumulative incidence rates for major bleeding (primary safety endpoint) and non-major bleeding (secondary safety endpoint) were 1.2%/year and 4.9%/year, respectively. Differences were noted between new and current users only for major bleeding event rate (1.7% vs. 1.1%/year, P = 0.0024). Comparisons with previous studies suggested that rivaroxaban is effective and safe for low-risk patients (0-1 CHADS 2 ), as shown for warfarin in the XANTUS international prospective post-marketing study. The EXPAND study demonstrated that low dosages of rivaroxaban for Japanese NVAF patients in real-world clinical practice, including those with CHADS 2 scores 0-1, resulted in low rates of stroke and SE, and major and non-major bleeding. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of Lifestyle on Asthma Control in Japanese Patients: Importance of Periodical Exercise and Raw Vegetable Diet

PubMed Central

Iikura, Motoyasu; Yi, Siyan; Ichimura, Yasunori; Hori, Ai; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro; Mizoue, Tetsuya; Kobayashi, Nobuyuki

2013-01-01

Background The avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients. Methods The study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted. Results The proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis. Conclusions Periodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients. PMID:23874577

Effect of lifestyle on asthma control in Japanese patients: importance of periodical exercise and raw vegetable diet.

PubMed

Iikura, Motoyasu; Yi, Siyan; Ichimura, Yasunori; Hori, Ai; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro; Mizoue, Tetsuya; Kobayashi, Nobuyuki

2013-01-01

The avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients. The study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted. The proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis. Periodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients.

Three hundred and eight nanometer excimer light therapy for alopecia universalis that is resistant to other treatments: A clinical study of 11 patients.

PubMed

Arakawa, Yukiyasu; Nomiyama, Tomoko; Katoh, Norito

2016-12-01

Three hundred and eight nanometer excimer light therapy has recently been reported to be effective against patchy alopecia areata (AA) in several clinical studies. However, these studies only included a few patients with severe forms of AA, and all of them exhibited poor outcomes. We further investigated the use of excimer light as a therapeutic option for cases of alopecia universalis (AU) that are resistant to other treatments. Eleven treatment-resistant AU patients were treated with a 308-nm excimer light at 2-week intervals for more than 16 sessions. Four patients achieved good responses and two patients exhibited poor responses. Three patients had Japanese skin type 1 and all of them achieved good responses. The radiation dose was increased until the patients exhibited marked erythema. The patients with Japanese skin type 3 who achieved good responses exhibited strong pigmentation at the irradiated sites. In conclusion, 308-nm excimer light therapy has significant effects on some AU patients who are resistant to other treatments and may be an alternative therapeutic option for AU. During the treatment of AU, high doses of radiation should be administrated until a strong inflammatory skin reaction is seen. © 2016 Japanese Dermatological Association.

Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open-label pilot study.

PubMed

Ohnuma, Tohru; Toda, Aiko; Kimoto, Ayako; Takebayashi, Yuto; Higashiyama, Ryoko; Tagata, Yuko; Ito, Masanobu; Ota, Tsuneyoshi; Shibata, Nobuto; Arai, Heii

2016-01-01

This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions. The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).

Prevalence, symptomatic features, and factors associated with sleep disturbance/insomnia in Japanese patients with type-2 diabetes.

PubMed

Narisawa, Hajime; Komada, Yoko; Miwa, Takashi; Shikuma, Junpei; Sakurai, Mamoru; Odawara, Masato; Inoue, Yuichi

2017-01-01

To clarify the prevalence and symptomatic characteristics of sleep disturbance/insomnia among type-2 diabetes mellitus (DM) Japanese patients. A cross-sectional survey of Japanese patients with the disorder was conducted. Participants consisted of 622 type-2 DM patients (mean 56.1±9.56 years) and 622 sex- and age-matched controls. Participants' scores in the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), the Japanese version of the 12-item Center for Epidemiologic Studies Depression Scale (CES-D), the Medical Outcomes Study 8-item Short Form Health Survey (SF-8), and the glycated hemoglobin A1c (HbA1c) of type-2 DM patients were analyzed. There were 253 poor sleepers (43.9%) in the type-2 DM group as a result of dichotomization with the PSQI-J cutoff total score of 5.5. The type-2 DM group recorded a higher mean PSQI-J total score ( P <0.01) and manifested poorer sleep maintenance. Poor sleepers in both groups had lower mental component summary from SF-8 (MCS), physical component summary from SF-8 (PCS), and CES-D than good sleepers, and good sleepers in both groups had higher MCS, PCS, and CES-D than poor sleepers. Higher body mass index, presence of smoking habit, and living alone were significantly associated with sleep disturbance/insomnia symptoms, but HbA1c was not associated with sleep disturbance/insomnia in the type-2 DM group. Individuals affected with type-2 DM are likely to experience sleep problems, characterized by disturbance in sleep maintenance. Sleep disturbance/insomnia symptoms in DM patients might considerably reduce health-related quality of life.

Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study.

PubMed

Kato, Ken; Ura, Takashi; Koizumi, Wasaburo; Iwasa, Satoru; Katada, Chikatoshi; Azuma, Mizutomo; Ishikura, Satoshi; Nakao, Yoshinori; Onuma, Hiroshi; Muro, Kei

2018-03-01

Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 on days 1-4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum-tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients.

PubMed

Oide, T; Ohara, S; Oguchi, K; Maruyama, M; Yazawa, M; Inoue, K; Sekijima, Y; Tokuda, T; Ikeda, S

2004-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) has so far been reported almost exclusively from the USA and Europe. We carried out this study to define the clinical characteristics of this syndrome in Japanese patients. Prospectively, we identified 13 Japanese patients with RS3PE (5 men and 8 women, age 72.7 +/- 11.8 years (mean +/- SD)) without underlying neoplasm. Their clinical features were summarized, pertinent laboratory data including serum/synovial interleukin-6 (IL-6) concentrations were obtained, and extensive radiologic studies using magnetic resonance imaging and 67gallium-citrate (67Ga) whole body scintigram were performed. All patients suffered from proximal arthralgia/myalgia in addition to typical distal symptoms of RS3PE, and all experienced systemic symptoms such as fever, malaise, and weight loss. In laboratory examinations, anemia and elevated inflammatory markers were often remarkable. Magnetic resonance imaging showed severe tenosynovitis of the hands. 67Ga-scintigram revealed radioisotope accumulation in both proximal and distal joints of the extremities. IL-6 activity was markedly elevated both in the serum (mean 82.4 +/- 62.1 (SD) pg/ml, normal range 0.157-2.94) and in the synovial fluid (mean 3350 +/- 633 (SD) pg/ml). Compared with cases reported previously from the USA/Europe, Japanese patients with RS3PE are characterized by more prominent systemic symptoms/signs associated with marked inflammatory responses including elevated IL-6 activity. All patients had proximal as well as distal synovitis which could be demonstrated by 67Ga-scintigram. These clinical features were very similar to those of polymyalgia rheumatica, suggesting that RS3PE and polymyalgia rheumatica are closely related disorders which may have a common pathogenesis.

Japanese encephalitis - the prospects for new treatments.

PubMed

Turtle, Lance; Solomon, Tom

2018-04-26

Japanese encephalitis is a mosquito-borne disease that occurs in Asia and is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus. Although many flaviviruses can cause encephalitis, JEV causes particularly severe neurological manifestations. The virus causes loss of more disability-adjusted life years than any other arthropod-borne virus owing to the frequent neurological sequelae of the condition. Despite substantial advances in our understanding of Japanese encephalitis from in vitro studies and animal models, studies of pathogenesis and treatment in humans are lagging behind. Few mechanistic studies have been conducted in humans, and only four clinical trials of therapies for Japanese encephalitis have taken place in the past 10 years despite an estimated incidence of 69,000 cases per year. Previous trials for Japanese encephalitis might have been too small to detect important benefits of potential treatments. Many potential treatment targets exist for Japanese encephalitis, and pathogenesis and virological studies have uncovered mechanisms by which these drugs could work. In this Review, we summarize the epidemiology, clinical features, prevention and treatment of Japanese encephalitis and focus on potential new therapeutic strategies, based on repurposing existing compounds that are already suitable for human use and could be trialled without delay. We use our newly improved understanding of Japanese encephalitis pathogenesis to posit potential treatments and outline some of the many challenges that remain in tackling the disease in humans.

Personality traits of Japanese patients in remission from an episode of primary unipolar depression.

PubMed

von Zerssen, D; Asukai, N; Tsuda, H; Ono, Y; Kizaki, Y; Cho, Y

1997-07-01

Personality traits were assessed by means of the Munich Personality Test (MPT) in 75 Japanese subjects, 27 patients in remission from an episode of moderate to severe primary unipolar depression, with melancholic features during one episode or more of the disorder, in 24 patients in remission from other non-organic mental disorders and in 24 healthy controls. Compared with healthy controls, unipolar depressives displayed decreased Frustration Tolerance and elevated Rigidity as well as a stronger Orientation towards Social Norms. No significant difference was found between patients in remission from either unipolar depression or other mental disorders. However, the increase in Rigidity in comparison with healthy subjects was significant in the depressives only whereas the other patients, in contrast to the depressives, had significantly lower scores in Extraversion than the healthy subjects. Our results in Japanese patients are similar to findings of previous German studies, including two high risk studies, in which the same assessment instrument was used. This suggests that, beyond cultural differences, Rigidity, possibly in combination with a strong Orientation towards Social Norms and a reduced Frustration Tolerance, is a stable vulnerability marker for at least the more severe forms of primary unipolar depression.

Seasonal allergic conjunctivitis induced by Japanese pear pollen.

PubMed

Yanagisawa, S; Nagaki, Y; Hiraki, S; Kadoi, C; Hayasaka, S; Teranishi, H

1999-01-01

To evaluate the ocular findings in patients with Japanese pear (Pyrus pyrifolia Nakai) pollinosis. Twenty-two farmers working on artificial pollination in Japanese pear orchards were examined for ocular itching, conjunctival conditions, presence of eosinophils in the conjunctival specimen, and nasal symptoms. Serum IgE antibody to Japanese pear pollen was determined in 16 farmers. Of the 22 subjects, 3 (Nos. 3, 4, and 13) exhibited ocular itching, conjunctival hyperemia, eosinophils in the conjunctival specimen, and positive serum IgE antibodies to Japanese pear pollen. In these patients, the conjunctivitis disappeared after treatment with topical cromoglycate. The present study demonstrated that seasonal allergic conjunctivitis may be induced by Japanese pear pollen (entomophilous flower pollen).

Current status of sperm banking for young cancer patients in Japanese nationwide survey.

PubMed

Yumura, Yasushi; Tsujimura, Akira; Okada, Hiroshi; Ota, Kuniaki; Kitazawa, Masahumi; Suzuki, Tatsuya; Kakinuma, Tosiyuki; Takae, Seido; Suzuki, Nao; Iwamoto, Teruaki

2018-02-02

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.

Efficacy and safety of canagliflozin in combination with insulin: a double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus.

PubMed

Inagaki, Nobuya; Harashima, Shin-Ichi; Maruyama, Nobuko; Kawaguchi, Yutaka; Goda, Maki; Iijima, Hiroaki

2016-06-18

Combination therapy with canagliflozin and insulin was investigated in a prescribed substudy of the canagliflozin Cardiovascular Assessment Study (CANVAS); however, it was not evaluated in Japanese patients with type 2 diabetes mellitus (T2DM). Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients, we determined the clinical benefit of such a combination therapy in Japanese patients. Patients who had inadequate glycemic control despite insulin, diet and exercise therapies were randomized into placebo (n = 70) and canagliflozin 100 mg (n = 76) groups that were administered once daily in addition to their prior insulin therapy in this double-blind, placebo-controlled study. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from the baseline to week 16. There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group (-0.97 ± 0.08 %) compared with the placebo group (0.13 ± 0.08 %) at week 16 [last observation carried forward (LOCF)]. The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen (premixed, long-acting and long-acting plus rapid- or short-acting). Compared with the placebo group, canagliflozin significantly decreased fasting plasma glucose levels (-34.1 ± 4.8 vs -1.4 ± 5.0 mg/dL) and body weights (-2.13 ± 0.25 vs 0.24 ± 0.26 %), and significantly increased HDL cholesterol (3.3 ± 1.0 vs -0.5 ± 1.0 mg/dL) and HOMA2- %B (10.15 ± 1.37 vs 0.88 ± 1.42 %). The overall incidence of adverse events was similar between the two groups. The incidence and incidence per subject-year exposure of hypoglycemia (hypoglycemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 % and 7.97) than in the placebo group (29.6 % and 4.51). However, hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by <10 % from the

Four Japanese male patients with juvenile retinoschisis: only three have mutations in the RS1 gene.

PubMed

Hayashi, Takaaki; Omoto, Satoshi; Takeuchi, Tomokazu; Kozaki, Kenichi; Ueoka, Yasuo; Kitahara, Kenji

2004-11-01

To describe the clinical phenotypes of four unrelated Japanese male patients with juvenile retinoschisis and to investigate occurrences of mutations in the RS1 gene. Observational case series and experimental study. Fundus examinations, fluorescein angiography, and single-flash electroretinography (ERG) were carried out. In one patient, optical coherence tomography (OCT) was performed. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction (PCR). The PCR products were purified and directly sequenced. The four affected patients showed cystoid- or wheel-like foveal changes with a little or no fluorescein leakage and negative b-wave patterns in both eyes. The OCT images of foveal retinoschisis disclosed that splitting occurs in the putative fibers of Henle. In three patients, we identified three different missense mutations (p.S73P, p.Y89C, p.R209C) in the functionally important discoidin domain of the RS1 gene. The p.S73P mutation has not been previously reported. In contrast, no nucleotide substitutions were detected in the fourth patient whose parents were unrelated and asymptomatic. No other member of this family for three generations has had juvenile retinoschisis. Because serine 73 is conserved in the mouse ortholog and other discoidin proteins, the proline 73 allele is therefore very likely to encode a defective retinoschisin. Although the inheritance pattern is uncertain in the patient without the RS1 mutation, the clinical and ERG findings were indistinguishable from those of patients with RS1 mutations. This finding points to the genetic heterogeneity of juvenile retinoschisis.

Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

PubMed Central

Seki, Kyoko; Senzaki, Kenzou; Tsuduki, Yasuo; Ioroi, Takeshi; Fujii, Michiko; Yamauchi, Hiroko; Shiraishi, Yukinari; Nakata, Izumi; Nishiguchi, Kohshi; Matsubayashi, Teruhisa; Takakubo, Yoshihide; Okamura, Noboru; Yamamori, Motohiro; Tamura, Takao; Sakaeda, Toshiyuki

2011-01-01

Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions. Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP. Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049). Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy. PMID:21448307

Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

PubMed

Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2015-02-01

The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and

Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.

PubMed

Arai, Yuuki; Maeda, Akiko; Hirami, Yasuhiko; Ishigami, Chie; Kosugi, Shinji; Mandai, Michiko; Kurimoto, Yasuo; Takahashi, Masayo

2015-01-01

The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.

(Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

PubMed Central

Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

2018-01-01

Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

Visual reproduction on the Wechsler Memory Scale-Revised as a predictor of Alzheimer's disease in Japanese patients with mild cognitive impairments.

PubMed

Hori, Takumi; Sanjo, Nobuo; Tomita, Makoto; Mizusawa, Hidehiro

2013-01-01

The Visual Reproduction (VR) test is used to assess mild cognitive impairment (MCI), but the characteristics of visual memory in Japanese MCI patients remain unclear. VR scores of 27 MCI patients were evaluated using the Wechsler Memory Scale-Revised. Scores of MCI, no-dementia, and Alzheimer's disease (AD) groups were then compared. The annual conversion rate of MCI to AD was 18.8%. Mean VR-I and VR-II baseline scores for MCI patients were 33.3 ± 5.6 and 20.5 ± 14.0, respectively. Mean VR-II scores for converted and nonconverted MCI patients were 7.2 ± 8.7 and 29.8 ± 9.3, respectively. It is likely that VR-II and VR-II/I scores are more sensitive for predicting conversion to AD in Japanese than in American MCI patients. Our results indicate that VR is a sensitive and useful measure for predicting the conversion of Japanese MCI patients to AD within 2 years. Copyright © 2013 S. Karger AG, Basel.

Cognitive behavioral therapy for depression in Japanese Parkinson’s disease patients: a pilot study

PubMed Central

Shinmei, Issei; Kobayashi, Kei; Oe, Yuki; Takagishi, Yuriko; Kanie, Ayako; Ito, Masaya; Takebayashi, Yoshitake; Murata, Miho; Horikoshi, Masaru; Dobkin, Roseanne D

2016-01-01

Objectives This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel. Methods Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey). Results Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =−1.02, 95% confidence interval =−1.62 to −0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention. Conclusion This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial. PMID:27354802

Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.

PubMed

Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz M; Tombal, Bertrand; Ueda, Takeshi

2016-05-01

To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL. © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on

Providing written information increases patient satisfaction: a web-based questionnaire survey of Japanese cancer survivors.

PubMed

Sakai, Hitomi; Katsumata, Noriyuki; Takahashi, Miyako

2017-07-01

The Institute of Medicine (IOM) of the United States recommends that all cancer survivors be provided with a survivorship care plan (SCP), which includes a patient treatment summary and a follow-up care plan. However, SCPs have not been widely adopted in Japan. To provide basic data necessary for implementing SCPs in Japan, we aimed to investigate the forms of clinical and survivorship-related information that Japanese cancer survivors receive from their healthcare providers, and to examine whether written information increases their satisfaction. We performed a cross-sectional online survey of cancer survivors who underwent acute cancer treatment and had at least one follow-up with a physician in the past year. Cancer survivors provided the elements and forms (verbally and/or written) of information they received, as well as the degree of satisfaction with the information provided. Responses were obtained from 545 cancer survivors. Information elements such as surgical procedure (98.3%), surgical outcome (98.1%), and names of administered chemotherapy agents (97.8%) were commonly provided, whereas mental care resources and providers (29.7%), effects on marital relationship and sexual health (35.7%), and effects on fertility (43.4%) were less common. A large proportion of cancer survivors received verbal information only. For 18 of 20 elements, except for effects on fertility and duration of hormonal therapy, satisfaction was significantly higher when both forms of information were provided (P < 0.05). Providing written and verbal explanations of clinical and survivorship-related information can better meet the needs of Japanese cancer survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

PubMed

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

Prevalence of scars and "mini-scars", and their impact on quality of life in Japanese patients with acne.

PubMed

Hayashi, Nobukazu; Miyachi, Yoshiki; Kawashima, Makoto

2015-07-01

There have been very few studies on the prevalence and severity of acne scars in Japanese patients. The aim of the present study was to investigate the prevalence of acne scars and their impact on the quality of life (QOL) in Japanese acne patients. Acne scars were classified as mini-scars (atrophic scars of ≥0.5 and <2 mm in diameter) atrophic scars (≥2 mm in diameter), and hypertrophic scars. The severity of acne and acne scars were evaluated. The background of patients and their QOL in relation to acne were assessed. Of 240 subjects, 218 (90.8%) had scars. All patients with scars had mini-scars; 61.2% and 14.2% of 240 had atrophic scars and hypertrophic scars, respectively. Severe scarring was found in patients who had experienced severe acne symptoms, although 15.0% of patients with scars had experienced only mild acne symptoms. The total Dermatology Life Quality Index score was significantly higher in patients with scars than in patients without scars (5.9 ± 4.4 vs 4.2 ± 4.1). Almost all the patients had small atrophic scars with a diameter of 0.5 or more and less than 2 mm, which we have termed "mini-scars". Acne scars had a negative impact on patient QOL. Early initiation of treatment is recommended to avoid acne scars. © 2015 Japanese Dermatological Association.

Effect of low-dose aspirin on primary prevention of cardiovascular events in Japanese diabetic patients at high risk.

PubMed

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Sugiyama, Seigo; Jinnouchi, Hideaki; Waki, Masako; Doi, Naofumi; Horii, Manabu; Kawata, Hiroyuki; Somekawa, Satoshi; Soeda, Tsunenari; Uemura, Shiro; Saito, Yoshihiko

2013-01-01

Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin's benefit in Japanese diabetic patients stratified by cardiovascular risk. In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58-1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after adjusting for potential confounding factors. Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk.

Cheilitis Glandularis: Two Case Reports of Asian-Japanese Men and Literature Review of Japanese Cases

PubMed Central

Yanagawa, Toru; Yamaguchi, Akira; Harada, Hiroyuki; Yamagata, Kenji; Ishibashi, Naomi; Noguchi, Masayuki; Onizawa, Kojiro; Bukawa, Hiroki

2011-01-01

Cheilitis glandularis (CG) is a rare disorder characterized by swelling of the lip with hyperplasia of the labial salivary glands. CG is most frequently encountered in the lower lip, in middle-aged to older Caucasian men; however Asian cases were rarely reported. In this paper we present two cases of CG in Asian-Japanese men. One was a 23-year-old male with CG of the superficial suppurative type. The other was a 54-year-old male with deep suppurative type. We also reviewed the Japanese cases of CG in the literature and discussed about clinical feature of Japanese CG. PMID:21991474

Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery.

PubMed

Imaizumi, Tsuyoshi; Obara, Shinju; Mogami, Midori; Iseki, Yuzo; Hasegawa, Makiko; Murakawa, Masahiro

2017-06-01

Intravenous (i.v.) acetaminophen is administered during surgery for postoperative analgesia. However, little information is available on the pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery under general anesthesia. The study was approved by the Institutional Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to undergo elective surgery under general anesthesia were enrolled after obtaining written informed consent. During surgery, 1 g of i.v. acetaminophen was administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16 samples per case) were measured at time points from 0-480 min after the start of administration (liquid chromatography-mass spectrometry/tandem mass spectrometry; limit of quantitation 0.1 μg/mL). The predictive performance of three published pharmacokinetic models was evaluated. Population pharmacokinetics were also analyzed using a nonlinear mixed-effect model based on the NONMEM program. Data from 12 patients who underwent endoscopic or lower limb procedures were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic model of i.v. acetaminophen reported by Würthwein et al. worked well. Using 185 datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two-compartment model with weight as a covariate but not age, sex, or creatinine clearance. The median prediction error and median absolute prediction error of the final model were -1 and 10%, respectively. A population pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed, with performance within acceptable ranges.

Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt-Hogg-Dubé syndrome.

PubMed

Furuya, Mitsuko; Yao, Masahiro; Tanaka, Reiko; Nagashima, Yoji; Kuroda, Naoto; Hasumi, Hisashi; Baba, Masaya; Matsushima, Jun; Nomura, Fumio; Nakatani, Yukio

2016-11-01

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder characterized by fibrofolliculomas, pulmonary cysts and renal cell carcinomas (RCCs). The affected individuals inherit germline mutations in the folliculin gene (FLCN). We investigated the mutation spectrum and clinicopathologic findings of 312 patients from 120 different families (119 Japanese and 1 Taiwanese). A total of 31 different FLCN sequence variants were identified. The majority were c.1285dupC (n = 34), c.1533_1536delGATG (n = 25), and c.1347_1353dupCCACCCT (n = 19). Almost all patients presented with pulmonary cysts. The incidence of RCCs in FLCN mutation carriers over the age of 40 was 34.8% (40/115). Fifty-five RCC lesions were surgically resected; most were either chromophobe RCC (n = 24; 43.6%) or hybrid oncocytic/chromophobe tumors (19; 34.5%). Seventy-six of 156 FLCN mutation carriers (120 probands and 36 sibs, 48.7%) had skin papules; however, cutaneous manifestations were so subtle that only one patient voluntarily consulted dermatologists. Japanese Asian BHD families have three FLCN mutational hotspots. Recurrent episodes of pneumothoraces are the major symptoms suggestive of a BHD diagnosis in our cohort. Characteristic features of lung and kidney lesions may be more informative than fibrofolliculomas as diagnostic criteria for BHD in the Japanese Asian population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients with type 2 diabetes mellitus.

PubMed

Kanto, Kousei; Ito, Hiroyuki; Noso, Shinsuke; Babaya, Naru; Hiromine, Yoshihisa; Taketomo, Yasunori; Toma, Junko; Niwano, Fumimaru; Yasutake, Sara; Kawabata, Yumiko; Ikegami, Hiroshi

2017-09-30

Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients. A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. Significant dose-dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side-effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. These results show that the efficacy of high-dose metformin is dose-dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Comparison of the efficacy and safety of 10-mg empagliflozin every day versus every other day in Japanese patients with Type 2 Diabetes Mellitus: a pilot trial.

PubMed

Obata, Fumiaki; Tani, Kenji; Yamaguchi, Harutaka; Tabata, Ryo; Bando, Hiroyasu; Imoto, Issei

2017-01-01

The terminal elimination half-life (t1/2) of empagliflozin is 13.1 hours. Accordingly, we hypothesized that the administration of empagliflozin every other day might improve glycemic control in patients with type 2 diabetes mellitus, not being inferior to the therapy every day. We investigated the clinical effects and safety of the addition of empagliflozin every day or every other day to type 2 diabetic patients with a poor control in glycemia. Thirteen Japanese patients diagnosed as type 2 diabetes mellitus recruited to this study. Subjects were divided into two groups; one was treatment with 10 mg of empagliflozin every day (Group A), the other was 10 mg of empagliflozin every other day (Group B). The comparable study of multiple clinical indexes between the 2 groups was made before and 8, 16, and 24 weeks after the treatment. After the treatment for 24 weeks, the HbA1c level was decreased both in group A (from 7.5%±1.1% to 6.5%±0.8%) and in group B (from 7.6%±0.8% to 7.2%±0.5%). This pilot trial suggested the possibility of 10-mg every other day administration with empagliflozin for Japanese patients with type 2 diabetes mellitus. J. Med. Invest. 64: 50-57, February, 2017.

Blood vessel invasion and other variables as predictors of long-term survival in Japanese and British patients with primary invasive breast cancer

PubMed Central

Kato, Takao; Pezzella, Francesco; Steers, Graham; Campo, Leticia; Leek, Russell D; Turley, Helen; Kameoka, Shingo; Nishikawa, Toshio; Harris, Adrian L; Gatter, Kevin C; Fox, Stephen

2014-01-01

This study was undertaken to investigate the associations of blood vessel invasion (BVI), lymphatic vessel invasion (LVI) or other variables and long-term survival in 173 Japanese and 184 British patients with primary invasive breast cancer, and whether they are associated with survival differences between Japanese and British patients. BVI was detected by objective methods, using both factor VIII-related antigen (F-VIII) staining and elastica van Gieson (E v G) staining. BVI was classified into three subtypes. 1) BVI e, BVI detected by E v G staining alone, 2) BVI f, BVI detected by F-VIII staining alone, 3) BVIef, BVI evaluated by combining BVIf and BVIe. LVI was also detected by objective methods, using lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) staining alone. There was a borderline significance between the frequencies for BVIef of British patients and those of Japanese patients (8.2% vs 3.5%; P = 0.06) but not for LVI (P = 0.36). British patients had a significantly worse relapse-free survival (RFS) and overall survival (OS) than Japanese patients (P < 0.01, P < 0.01, respectively) even though their tumors were smaller and more ER-positive with a similar prevalence of lymph-node involvement. LVI was not significantly associated with RFS and OS, however, BVIef positive tumors had a significantly worse RFS and OS compared with BVIef negative patients, after statistical adjustment for the other variables (P = 0.02, P = 0.01, respectively). The present study shows that BVIef variability might contribute to the Japanese and British disparities in breast cancer outcomes. PMID:25550840

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

PubMed Central

Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

PubMed

Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

2014-11-01

The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

ASP8273 tolerability and antitumor activity in TKI-naive Japanese patients with EGFR mutation-positive non-small cell lung cancer.

PubMed

Azuma, Koichi; Nishio, Makoto; Hayashi, Hidetoshi; Kiura, Katsuyuki; Satouchi, Miyako; Sugawara, Shunichi; Hida, Toyoaki; Iwamoto, Yasuo; Inoue, Akira; Takeda, Koji; Ikeda, Satoshi; Nakagawa, Tomoki; Takeda, Kentaro; Asahina, Seitaro; Komatsu, Kanji; Morita, Satoshi; Fukuoka, Masahiro; Nakagawa, Kazuhiko

2018-05-28

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKI). ASP8273 is an orally administered, irreversible EGFR-TKI that inhibits EGFR activating mutations and has demonstrated clinical activity in patients with EGFR mutation-positive NSCLC. EGFR-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, Phase 2 study (NCT02500927). Patients received ASP8273 300mg once daily until discontinuation criteria were met. The primary endpoint was to determine the safety of ASP8273 300mg; secondary endpoint was antitumor activity defined by RECIST v1.1. Thirty-one patients (12M/19F; median age 64 years [range: 31-82]) with EGFR mutation-positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 2 (7%) had L861Q mutation and 5 (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment-emergent adverse event was diarrhea [n=24, 77%]. All patients had at least 1 post-baseline scan; 1 patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Once-daily ASP8273 300 mg was generally well tolerated and demonstrated antitumor activity in TKI-naïve Japanese patients with EGFR mutation-positive NSCLC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

PubMed

Gejyo, Fumitake; Saito, Akira; Akizawa, Tadao; Akiba, Takashi; Sakai, Tatsuya; Suzuki, Masashi; Nishi, Shinichi; Tsubakihara, Yoshiharu; Hirakata, Hideki; Bessho, Masami

2004-12-01

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic

Development of the Japanese DOLOPLUS-2: a pain assessment scale for the elderly with Alzheimer's disease.

PubMed

Ando, Chiaki; Hishinuma, Michiko

2010-09-01

Japanese DOLOPLUS-2 can be used reliably in clinical settings to measure the pain AD patients may be experiencing. However, the final version of the Japanese DOLOPLUS-2 needs to be validated in a larger patient cohort in future studies. © 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.

Evaluation of scoring models for identifying the need for therapeutic intervention of upper gastrointestinal bleeding: A new prediction score model for Japanese patients.

PubMed

Iino, Chikara; Mikami, Tatsuya; Igarashi, Takasato; Aihara, Tomoyuki; Ishii, Kentaro; Sakamoto, Jyuichi; Tono, Hiroshi; Fukuda, Shinsaku

2016-11-01

Multiple scoring systems have been developed to predict outcomes in patients with upper gastrointestinal bleeding. We determined how well these and a newly established scoring model predict the need for therapeutic intervention, excluding transfusion, in Japanese patients with upper gastrointestinal bleeding. We reviewed data from 212 consecutive patients with upper gastrointestinal bleeding. Patients requiring endoscopic intervention, operation, or interventional radiology were allocated to the therapeutic intervention group. Firstly, we compared areas under the curve for the Glasgow-Blatchford, Clinical Rockall, and AIMS65 scores. Secondly, the scores and factors likely associated with upper gastrointestinal bleeding were analyzed with a logistic regression analysis to form a new scoring model. Thirdly, the new model and the existing model were investigated to evaluate their usefulness. Therapeutic intervention was required in 109 patients (51.4%). The Glasgow-Blatchford score was superior to both the Clinical Rockall and AIMS65 scores for predicting therapeutic intervention need (area under the curve, 0.75 [95% confidence interval, 0.69-0.81] vs 0.53 [0.46-0.61] and 0.52 [0.44-0.60], respectively). Multivariate logistic regression analysis retained seven significant predictors in the model: systolic blood pressure <100 mmHg, syncope, hematemesis, hemoglobin <10 g/dL, blood urea nitrogen ≥22.4 mg/dL, estimated glomerular filtration rate ≤ 60 mL/min per 1.73 m 2 , and antiplatelet medication. Based on these variables, we established a new scoring model with superior discrimination to those of existing scoring systems (area under the curve, 0.85 [0.80-0.90]). We developed a superior scoring model for identifying therapeutic intervention need in Japanese patients with upper gastrointestinal bleeding. © 2016 Japan Gastroenterological Endoscopy Society.

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

PubMed

Hatano, Koji; Nishimura, Kazuo; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Uemura, Motohide; Oka, Daizo; Nakayama, Masashi; Takayama, Hitoshi; Shimizu, Kiyonori; Meguro, Norio; Tanigawa, Tsuyoshi; Yamaguchi, Seiji; Tsujimura, Akira; Nonomura, Norio

2013-08-01

A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation.

PubMed

Hirano, Makito; Nakamura, Yusaku; Saigoh, Kazumasa; Sakamoto, Hikaru; Ueno, Shuichi; Isono, Chiharu; Mitsui, Yoshiyuki; Kusunoki, Susumu

2015-03-01

Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

PubMed

Uchiyama, Shinichiro; Ishizuka, Naoki; Shimada, Kazuyuki; Teramoto, Tamio; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Minematsu, Kazuo; Matsumoto, Masayasu; Ikeda, Yasuo

2016-06-01

The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849. © 2016 American Heart Association, Inc.

Wolfram Syndrome in the Japanese Population; Molecular Analysis of WFS1 Gene and Characterization of Clinical Features

PubMed Central

Inoue, Hiroshi; Okuya, Shigeru; Ohta, Yasuharu; Akiyama, Masaru; Taguchi, Akihiko; Kora, Yukari; Okayama, Naoko; Yamada, Yuichiro; Wada, Yasuhiko; Amemiya, Shin; Sugihara, Shigetaka; Nakao, Yuzo; Oka, Yoshitomo; Tanizawa, Yukio

2014-01-01

Background Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene (WFS1). However, the phenotypic pleiomorphism, rarity and molecular complexity of this disease complicate our efforts to understand WFS. To address this limitation, we aimed to describe complications and to elucidate the contributions of WFS1 mutations to clinical manifestations in Japanese patients with WFS. Methodology The minimal ascertainment criterion for diagnosing WFS was having both early onset diabetes mellitus and bilateral optic atrophy. Genetic analysis for WFS1 was performed by direct sequencing. Principal Findings Sixty-seven patients were identified nationally for a prevalence of one per 710,000, with 33 patients (49%) having all 4 components of DIDMOAD. In 40 subjects who agreed to participate in this investigation from 30 unrelated families, the earliest manifestation was DM at a median age of 8.7 years, followed by OA at a median age of 15.8 years. However, either OA or DI was the first diagnosed feature in 6 subjects. In 10, features other than DM predated OA. Twenty-seven patients (67.5%) had a broad spectrum of recessive mutations in WFS1. Two patients had mutations in only one allele. Eleven patients (27.5%) had intact WFS1 alleles. Ages at onset of both DM and OA in patients with recessive WFS1 mutations were indistinguishable from those in patients without WFS1 mutations. In the patients with predicted complete loss-of-function mutations, ages at the onsets of both DM and OA were significantly earlier than those in patients with predicted partial-loss-of function mutations. Conclusion/Significance This study emphasizes the clinical and genetic heterogeneity in patients with WFS. Genotype-phenotype correlations may exist in patients

Blood pressure differences between office and home settings among Japanese normotensive subjects and hypertensive patients.

PubMed

Mori, Hisao; Ukai, Hiroshi; Yamamoto, Hareaki; Yuasa, Shouhei; Suzuki, Yoshiro; Chin, Keiichi; Katsumata, Takuma; Umemura, Satoshi

2017-03-01

This study attempted to clarify the differences in blood pressure (BP) between the office (clinic) and home settings in patients with controlled, sustained, masked or white-coat hypertension. The following formula was used: office mean systolic BP (omSBP)-mean morning home SBP (mmhSBP)/office mean diastolic BP (omDBP)-mean morning home DBP (mmhDBP). The paired t-test was used for statistical analysis. The omSBP-mmhSBP/omDBP-mmhDBP calculation yielded the following results: among normotensive subjects, -1.1±11.2/-1.7±8.5 mm Hg (mean SBP and mean DBP were higher at home than in the office; n=451, P=0.038 in SBP, P=0.000 in DBP); in controlled hypertensive patients, -0.42±10.9/-2.2±8.2 mm Hg (n=1362, P=0.160 in SBP, P=0.000 in DBP); among sustained hypertensive patients, 5.6±14.7/0.048±9.9 mm Hg (n=1370, P=0.000 in SBP, P=0.857 in DBP); in masked hypertensive patients, -15.3±12.9/-9.3±9.5 mm Hg (n=1308, both P=0.000); and among white-coat hypertensive patients, 23.7±13.2/8.2±9.1 mm Hg (n=580, both P=0.000). Our results showed a difference of 5 mm Hg in SBP among sustained hypertensive patients, as recommended by the Japanese Society of Hypertension Guidelines for the Management of Hypertension; however, in other hypertensive patient types, the differences in SBP and DBP between office and home measurements differed by >5 mm Hg. Office and home BP measurements should be interpreted cautiously, keeping in mind the clinical setting.

Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

PubMed

Nakamura, T; Fukunaga, M; Nakano, T; Kishimoto, H; Ito, M; Hagino, H; Sone, T; Taguchi, A; Tanaka, S; Ohashi, M; Ota, Y; Shiraki, M

2017-01-01

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

First experience of using new adaptive servo-ventilation device for Cheyne-Stokes respiration with central sleep apnea among Japanese patients with congestive heart failure: report of 4 clinical cases.

PubMed

Kasai, Takatoshi; Narui, Koji; Dohi, Tomotaka; Takaya, Hisashi; Yanagisawa, Naotake; Dungan, George; Ishiwata, Sugao; Ohno, Minoru; Ymaguchi, Tetsu; Momomura, Shin-ichi

2006-09-01

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in congestive heart failure (CHF) is generally considered a poor prognostic indicator, but treatment of CSR-CSA using an adaptive servo-ventilation (ASV) device has been developed. This is the first evaluation of its use in the management of CSR-CSA in Japanese CHF patients. Four CHF patients with CSR-CSA that was unresponsive to conventional positive airway pressure (CPAP) underwent 3 nights of polysomnography: baseline, CPAP or bi-level PAP, and on the ASV. The apnea - hypopnea index (AHI) and central-AHI (CAHI) were markedly improved on ASV (AHI 62.7+/-10.1 to 5.9+/-2.2 /h, p=0.0006, CAHI 54.5+/-6.7 to 5.6+/-2.3 /h, p=0.007). In addition, the sleep quality improved significantly on ASV, including arousal index (62.0+/-10.5 to 18.7 +/-6.2 /h, p=0.012), percentage of slow-wave sleep (2.6+/-2.6 to 19.4+/-4.8 %, p=0.042). ASV markedly improved CSR-CSA in patients with CHF. It is a promising treatment for Japanese patients with CHF.

Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4-12 Years.

PubMed

Katsunuma, Toshio; Fujisawa, Takao; Mizuho, Nagao; Akira, Akasawa; Nomura, Ichiro; Yamaoka, Akiko; Kondo, Hisashi; Masuda, Kei; Yamaguchi, Koichi; Terada, Akihiko; Ikeda, Masanori; Nishioka, Kenji; Adachi, Yuichi; Kurihara, Kazuyuki

2013-01-01

Few studies have examined the efficacy or safety of a transdermal β2 agonist as add-on medicationto long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients. In this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2 mg daily) or oral sustained-release theophylline (usual dose, 4-5 mg_kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events. Thirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group. These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy. © 2013 Japanese Society of Allergology.

Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small cell lung cancer: AURA3 trial.

PubMed

Akamatsu, Hiroaki; Katakami, Nobuyuki; Okamoto, Isamu; Kato, Terufumi; Kim, Young Hak; Imamura, Fumio; Shinkai, Masaharu; Hodge, Rachel A; Uchida, Hirohiko; Hida, Toyoaki

2018-04-26

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase 3 study comparing the efficacy of osimertinib (80 mg/day) with platinum-based therapy plus pemetrexed (500 mg/m 2 ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary endpoint was progression-free survival (PFS) based on investigator assessment. PFS improvement was clinically meaningful in the osimertinib group (n=41) versus the platinum-pemetrexed group (n=22; hazard ratio 0.27, 95% confidence interval 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in five patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR mutant and T790M NSCLC whose disease has progressed following first-line EGFR-TKI treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessment of mortality by qSOFA in patients with sepsis outside ICU: A post hoc subgroup analysis by the Japanese Association for Acute Medicine Sepsis Registry Study Group.

PubMed

Umemura, Yutaka; Ogura, Hiroshi; Gando, Satoshi; Kushimoto, Shigeki; Saitoh, Daizoh; Mayumi, Toshihiko; Fujishima, Seitaro; Abe, Toshikazu; Ikeda, Hiroto; Kotani, Joji; Miki, Yasuo; Shiraishi, Shin-Ichiro; Shiraishi, Atsushi; Suzuki, Koichiro; Suzuki, Yasushi; Takeyama, Naoshi; Takuma, Kiyotsugu; Tsuruta, Ryosuke; Yamaguchi, Yoshihiro; Yamashita, Norio; Aikawa, Naoki

2017-11-01

Quick sequential organ failure assessment (qSOFA) was proposed in the new sepsis definition (Sepsis-3). Although qSOFA was created to identify patients with suspected infection and likely to have poor outcomes, the clinical utility of qSOFA to screen sepsis has not been fully evaluated. We investigated the number of patients diagnosed as having severe sepsis who could not be identified by the qSOFA criteria and what clinical signs could complement the qSOFA score. This retrospective analysis of a multicenter prospective registry included adult patients with severe sepsis diagnosed outside the intensive care unit (ICU) by conventional criteria proposed in 2003. We conducted receiver operating characteristic (ROC) analyses to assess the predictive value for in-hospital mortality and compared clinical characteristics between survivors and non-survivors with qSOFA score ≤ 1 point (qSOFA-negative). Among 387 eligible patients, 63 (16.3%) patients were categorized as qSOFA-negative, and 10 (15.9%) of these patients died. The area under the ROC curve for the qSOFA score was 0.615, which was superior to that for the systemic inflammatory response syndrome score (0.531, P = 0.019) but inferior to that for the SOFA score (0.702, P = 0.005). Multivariate logistic regression analysis showed that hypothermia might be associated with poor outcome independently of qSOFA criteria. Our findings suggested that qSOFA had a suboptimal level of predictive value outside the ICU and could not identify 16.3% of patients who were once actually diagnosed with sepsis. Hypothermia might be associated with an increased risk of death that cannot be identified by qSOFA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Lifestyle changes of Japanese people on overseas assignment in Michigan, USA.

PubMed

Kitamura, Kazuya; Fetters, Michael D; Sano, Kiyoshi; Sato, Juichi; Ban, Nobutaro

2009-07-16

Temporary work assignments in the United States (US) are widely considered to have negative health outcomes on Asians mostly due to adverse changes in diet and exercise, though there is little research on this phenomenon. This study investigated the impact of lifestyle changes on the biological and psychological health and health behaviours of Japanese people on temporary assignments in the US. In this cross sectional survey, we distributed a 38 item self-administered questionnaire addressing health habits, mental health function, lifestyle changes and dietary habits to adult Japanese patients presenting for general physicals at a family medicine clinic serving Japanese patients. We conducted simple statistics and regression analysis between length of stay and other health outcomes to determine whether length of residence in the US was predictive of negative lifestyle changes. Most participants reported increased caloric intake, weight gain, and less exercise. They also reported increased time with family. More women than men reported physical symptoms and anxiety related to stress. Smoking and alcohol intake were essentially unchanged. No associations were identified between length of residence in the US and health lifestyle habits or other health outcomes. Negative lifestyle changes occur in diet and exercise for overseas Japanese people, but a positive change in increased family time was found. Women appear to be at a greater risk for somatic disorders than men. As duration of stay does not appear predictive of adverse changes, clinicians should advise patients going abroad of these risks regardless of the term of the work assignment.

Influence of facial convexity on facial attractiveness in Japanese.

PubMed

Ioi, H; Nakata, S; Nakasima, A; Counts, Al

2007-11-01

The purpose of this study was to assess and determine the range of the top three most-favored facial profiles for each sex from a series of varying facial convexity, and to evaluate the clinically acceptable facial profiles for Japanese adults. Questionnaire-based study. Silhouettes of average male and female profiles were constructed from the profiles of 30 Japanese males and females with normal occlusions. Chin positions were protruded or retruded by 2 degrees , 4 degrees , 6 degrees , 8 degrees and 10 degrees , respectively, from the average profile. Forty-one orthodontists and 50 dental students were asked to select the three most-favored profiles for each sex, and they were also asked to indicate whether they would seek surgical orthodontic treatment if that image represented their own profile. For males, both the orthodontists and dental students chose the average profile as the most-favored profile. For females, both the orthodontists and dental students chose a slightly more retruded chin position as the most-favored profile. Japanese raters tended to choose class II profiles as more acceptable profiles than class III profiles for both males and females. These findings suggest that Japanese patients with class III profiles tend to seek surgical orthodontic treatment more often.

Clinical significance of the "galaxy sign" in patients with pulmonary sarcoidosis in a Japanese single-center cohort.

PubMed

Koide, Takashi; Saraya, Takeshi; Tsukahara, Yayoi; Bonella, Francesco; Börner, Eda; Ishida, Manabu; Ogawa, Yukari; Hirukawa, Ichiro; Oda, Miku; Shimoda, Masafumi; Ohkuma, Kosuke; Fujiwara, Masachika; Takata, Saori; Yokoyama, Takuma; Kurai, Daisuke; Ishii, Haruyuki; Goto, Hajime; Takizawa, Hajime

2016-10-07

The galaxy sign is an irregularly marginated pulmonary nodule formed by a confluence of multiple small nodules, and it is a diagnostic radiological finding for pulmonary sarcoidosis. However, the clinical significance of the galaxy sign for sarcoidosis has been poorly investigated. This study aimed to investigate the clinical significance and detailed radiological features of the galaxy sign in patients with pulmonary sarcoidosis. We retrospectively reviewed 87 patients with biopsy-proven sarcoidosis and 108 patients with pulmonary tuberculosis. Galaxy sign incidence was assessed on thoracic high-resolution computed tomography (HRCT) images from each group. Correlations of galaxy sign with clinical characteristics and disease outcomes were evaluated for patients with sarcoidosis. HRCT findings were available for 65 of 87 patients with pulmonary sarcoidosis and all 108 patients with pulmonary tuberculosis. Galaxy sign incidence was significantly higher in patients with pulmonary sarcoidosis (n=15, 23.1%) than in those with pulmonary tuberculosis (n=2, 1.9%, p<0.001). Among the 65 patients with pulmonary sarcoidosis, those with galaxy signs (n=15) were significantly younger (median: 32 years, interquartile range [IQR] 28-38 years) than those without (n=50) (median: 62 years, IQR 37.7-73 years). The CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) was also significantly lower in the former group (median: 2.6, IQR 2.0-3.9 vs. median 5.8, IQR 3.7-8.6, p<0.001). Galaxy signs are associated with younger age and low BALF CD4/CD8 ratio but not disease severity.

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

PubMed

Shimura, Shino; Ishimura, Norihisa; Tanimura, Takashi; Yuki, Takafumi; Miyake, Tatsuya; Kushiyama, Yoshinori; Sato, Shuichi; Fujishiro, Hirofumi; Ishihara, Shunji; Komatsu, Taisuke; Kaneto, Eiji; Izumi, Akio; Ishikawa, Noriyoshi; Maruyama, Riruke; Kinoshita, Yoshikazu

2014-01-01

The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive. © 2014 S. Karger AG, Basel.

Factors related to coping strategies during Japanese physical therapy students' clinical practice.

PubMed

Higuchi, Daisuke; Echigo, Ayumi

2017-08-01

[Purpose] This study aimed to identify social skills and support that are related to the coping strategies Janpanese physical therapy students use during their clinical practice. [Subjects and Methods] Third-year students who were finished with their clinical practice participated. Self-administered questionnaires were used, including the daily life skill scale, social support scale, and tri-axial coping scale. Spearman's partial correlation coefficients were calculated between social skills, support of daily living, and coping strategies used during the clinical practice, while controlling for gender. [Results] A total of 56 completed questionnaires (median of age: 21 years; 27 males). Social skills during personal situations-knowledge summarization, self-esteem, and positive thinking-were significantly, positively correlated with planning and affirmative interpreting strategies to approach stressors regarding clinical practice, and negatively related to giving up strategies to avoid stressors. Intimacy, leadership, and empathy (social skills during interpersonal situations) were significantly, positively correlated with the following responses to approach stressors: catharsis, information gathering, and affirmative interpreting. Moreover, emotional/companionship social support was significantly, positively correlated with all avoidant coping strategies. [Conclusion] Japanese physical therapy students who had low personal and interpersonal social skills and excess emotional/companionship support in daily life tend to select avoidance, not approach, coping strategies during clinical practice.

A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia.

PubMed

Tomiyama, Y; Miyakawa, Y; Okamoto, S; Katsutani, S; Kimura, A; Okoshi, Y; Ninomiya, H; Kosugi, H; Nomura, S; Ozaki, K; Ikeda, Y; Hattori, T; Katsura, K; Kanakura, Y

2012-05-01

Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent. To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe. We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 μL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag). The response rate (platelet count of ≥ 50,000 μL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423). © 2012 International Society on Thrombosis and Haemostasis.

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical

Age and Prevalence of Esophageal Reflux Disease in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Ikeda, Yoshio; Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Senba, Hidenori; Yamamoto, Yasunori; Arimitsu, Eiji; Yagi, Sen; Utsunomiya, Hiroki; Tanaka, Keiko; Takeshita, Eiji; Matsuura, Bunzo; Miyake, Yoshihiro; Hiasa, Yoichi

2016-12-01

Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 ≤ age < 56, (2) 56 ≤ age < 64, (3) 64 ≤ age < 71, and (4) 71 ≤ age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score ≥4. The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 ≤ age < 64, 64 ≤ age < 71, and ≥71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H 2 -receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA.

Japanese Competitiveness and Japanese Management.

ERIC Educational Resources Information Center

Minabe, Shigeo

1986-01-01

Analyzes and compares Japanese and American industrial policy and labor practices. Proposes that certain aspects of the Japanese system be adapted by American businesses for purpose of increasing international competitiveness. Proposes specific actions and plans for both the Japanese and American systems. (ML)

Analysis of the Japanese subgroup in LEOPOLD II: a phase 2/3 study of BAY 81-8973, a new recombinant factor VIII product.

PubMed

Fujii, Teruhisa; Hanabusa, Hideji; Shima, Midori; Morinaga, Takeshi; Fukutake, Katsuyuki

2017-03-01

BAY 81-8973, a new full length recombinant FVIII product, has been developed for prophylaxis and on-demand therapy in patients with hemophilia A. LEOPOLD II was a phase 2/3 study comparing prophylaxis versus on-demand treatment with BAY 81-8973. The analysis herein evaluated the clinical profile in Japanese subjects enrolled in LEOPOLD II. The LEOPOLD II was an open-label randomized crossover study. Our analysis evaluated the efficacy using the annualized bleeding rate, safety, and pharmacokinetics in Japanese subjects with severe hemophilia A enrolled in LEOPOLD II. The median annualized bleeding rate was 59.9/year in the on-demand group and 1.9/year in the prophylaxis group for Japanese subjects. There were no study drug-related adverse events in the Japanese subjects. None of the subjects developed FVIII inhibitors. There were no apparent clinical differences in efficacy, safety, and pharmacokinetics between the Japanese and the non-Japanese subjects. Data for the Japanese subjects showed annualized bleeding rates to be remarkably lower in the prophylaxis group compared to the on-demand group and that BAY 81-8973 exhibited a good safety profile and tolerability. These results were similar for the non-Japanese subjects. The results support adoption of BAY 81-8973 for treatment of Japanese subjects with severe hemophilia A.

Relationship between environmental factors, age of onset and familial history in Japanese patients with psoriasis.

PubMed

Bayaraa, Bolortuya; Imafuku, Shinichi

2018-06-01

Psoriasis is a chronic inflammatory disease that often involves the skin and joints. Psoriasis develops at any age and the distribution of age of onset of psoriasis is bimodal in Japan. Also, male predominance is distinct in Japanese psoriatic patients. To clarify the relationship between sex difference and habitual/environmental status, age and incidence of familial psoriasis, we analyzed data from the Fukuoka University Psoriasis Registry. A total of 1120 Japanese patients (751 men, 369 women) were analyzed. The male/female ratio was 2.03:1. Smoking and drinking habit, known as risk factors of psoriasis, were significantly more prevalent in men. Age-specific psoriasis-onset rate standardized by population showed bimodal distribution in both men and women; the younger peak was in their 30s for men and 10s in women; the second peak was in the 50s for both sexes. A familial history of psoriasis was seen in 6.3% of patients overall; however, female patients showed a significantly higher rate (8.7%) compared with men (5.1%, P = 0.024). When stratified by age of onset, the frequency of familial history was much higher among women with onset at less than 30 years (15.4%), compared with 30 years or more (5.3%, P = 0.0026). Our data suggest that genetic factors have a stronger influence in young women who experience fewer environmental factors such as smoking and drinking. This is the first study to show that there is a difference in the incidence of familial psoriasis depending on age of onset of psoriasis in Japan. © 2018 Japanese Dermatological Association.

Tumor development in Japanese patients with Lynch syndrome

PubMed Central

Horiguchi, Shin-ichiro; Yamada, Rin; Takao, Misato; Iijima, Takeru; Wakaume, Rika; Aruga, Tomoyuki; Tabata, Taku; Koizumi, Koichi

2018-01-01

Background Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients. Methods This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Results The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19−65) and 44 (range, 24−66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9−63.3%] for CRC, 17.4% (95% CI, 5.2−35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4−13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this. Conclusion Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients. PMID:29672549

Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients

PubMed Central

Tamura, Yasuhiro; Funaki, Yasushi; Izawa, Shinya; Iida, Akihito; Yamaguchi, Yoshiharu; Adachi, Kazunori; Ogasawara, Naotaka; Sasaki, Makoto; Kaneko, Hiroshi; Kasugai, Kunio

2015-01-01

AIM: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. METHODS: A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. RESULTS: Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. CONCLUSION: Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them. PMID:25945016

Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

PubMed

Tamura, Yasuhiro; Funaki, Yasushi; Izawa, Shinya; Iida, Akihito; Yamaguchi, Yoshiharu; Adachi, Kazunori; Ogasawara, Naotaka; Sasaki, Makoto; Kaneko, Hiroshi; Kasugai, Kunio

2015-04-28

To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

Lack of a significant impact of Gag-Protease-mediated HIV-1 replication capacity on clinical parameters in treatment-naive Japanese individuals.

PubMed

Sakai, Keiko; Chikata, Takayuki; Brumme, Zabrina L; Brumme, Chanson J; Gatanaga, Hiroyuki; Gatanag, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2015-11-19

HLA class I-associated escape mutations in HIV-1 Gag can reduce viral replication, suggesting that associated fitness costs could impact HIV-1 disease progression. Previous studies in North American and African cohorts have reported reduced Gag-Protease mediated viral replication capacity (Gag-Pro RC) in individuals expressing protective HLA class I alleles including HLA-B*57:01, B*27:05, and B*81:01. These studies also reported significant positive associations between Gag-Pro RCs and plasma viral load (pVL). However, these HLA alleles are virtually absent in Japan, and the importance of Gag as an immune target is not clearly defined in this population. We generated chimeric NL4-3 viruses carrying patient-derived Gag-Protease from 306 treatment-naive Japanese individuals chronically infected with HIV-1 subtype B. We analyzed associations between Gag-Pro RC and clinical markers of HIV-1 infection and host HLA expression. We observed no significant correlation between Gag-Pro RC and pVL in Japan in the overall cohort. However, upon exclusion of individuals expressing Japanese protective alleles HLA-B*52:01 and B*67:01, Gag-Pro RC correlated positively with pVL and negatively with CD4 T-cell count. Our results thus contrast with studies from other global cohorts reporting significantly lower Gag-Pro RC among persons expressing protective HLA alleles, and positive relationships between Gag-Pro RC and pVL in the overall study populations. We also identified five amino acids in Gag-Protease significantly associated with Gag-Pro RC, whose effects on RC were confirmed by site-directed mutagenesis. However, of the four mutations that decreased Gag-Pro RC, none were associated with reductions in pVL in Japan though two were associated with lower pVL in North America. These data indicate that Gag fitness does not affect clinical outcomes in subjects with protective HLA class I alleles as well as the whole Japanese population. Moreover, the impact of Gag fitness costs on HIV

Clinical Features of Idiopathic Parotid Pain Triggered by the First Bite in Japanese Patients with Type 2 Diabetes: A Case Study of Nine Patients.

PubMed

Chiba, Masatoshi; Hirotani, Hiroaki; Takahashi, Tetsu

2018-01-01

First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0-10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1-10 min after meals in six patients. IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different.

Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma.

PubMed

Yamazaki, N; Uhara, H; Fukushima, S; Uchi, H; Shibagaki, N; Kiyohara, Y; Tsutsumida, A; Namikawa, K; Okuyama, R; Otsuka, Y; Tokudome, T

2015-11-01

Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients. Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m(2) every 3 weeks for four doses (q3w × 4), followed by DTIC q3w × 4 and then IPI every 12 weeks until disease progression or intolerable toxicity. All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities. IPI 10 mg/kg plus DTIC 850 mg/m(2) was not considered tolerable in the Japanese patient population. ClinicalTrials.gov identifier: NCT01681212.

Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy.

PubMed

Yoshida, Naruo; Hirata, Hirokuni; Watanabe, Mineaki; Sugiyama, Kumiya; Arima, Masafumi; Fukushima, Yasutsugu; Ishii, Yoshiki

2015-07-01

Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P < 0.01) between hornet (R = 0.92) or paper wasp venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients. The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan. Copyright © 2015 Japanese Society of Allergology. Production and hosting by

Development and validation of a new instrument for testing functional health literacy in Japanese adults.

PubMed

Nakagami, Katsuyuki; Yamauchi, Toyoaki; Noguchi, Hiroyuki; Maeda, Tohru; Nakagami, Tomoko

2014-06-01

This study aimed to develop a reliable and valid measure of functional health literacy in a Japanese clinical setting. Test development consisted of three phases: generation of an item pool, consultation with experts to assess content validity, and comparison with external criteria (the Japanese Health Knowledge Test) to assess criterion validity. A trial version of the test was administered to 535 Japanese outpatients. Internal consistency reliability, calculated by Cronbach's alpha, was 0.81, and concurrent validity was moderate. Receiver Operating Characteristics and Item Response Theory were used to classify patients as having adequate, marginal, or inadequate functional health literacy. Both inadequate and marginal functional health literacy were associated with older age, lower income, lower educational attainment, and poor health knowledge. The time required to complete the test was 10-15 min. This test should enable health workers to better identify patients with inadequate health literacy. © 2013 Wiley Publishing Asia Pty Ltd.

Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52-week, phase 3, multicenter, open-label study.

PubMed

Sano, Shigetoshi; Kubo, Hiroshi; Morishima, Hitomi; Goto, Ryosuke; Zheng, Richuan; Nakagawa, Hidemi

2018-05-01

Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open-label study was to evaluate efficacy and safety of guselkumab, a human interleukin-23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end-point was the proportion of patients achieving treatment success (Clinical Global Impression score of "very much improved", "much improved" or "minimally improved") at week 16. Safety evaluations included assessment of treatment-emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end-points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52. © 2018 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PubMed

Sugimoto, T; Sada, M; Miyamoto, T; Yao, H

2003-08-01

autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Tsuji-Akimoto, Sachiko; Hamada, Shinsuke; Yabe, Ichiro; Tamura, Itaru; Otsuki, Mika; Kobashi, Syoji; Sasaki, Hidenao

2010-12-01

Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients' writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.

Factors associated with progression of diabetic nephropathy in Japanese elderly patients with type 2 diabetes: sub-analysis of the Japanese Elderly Diabetes Intervention Trial.

PubMed

Araki, Shin-ichi; Nishio, Yoshihiko; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Iimuro, Satoshi; Ohashi, Yasuo; Uzu, Takashi; Maegawa, Hiroshi; Kashiwagi, Atsunori; Ito, Hideki

2012-04-01

Diabetic nephropathy is a serious complication in patients with type 2 diabetes. The aim of this study was to explore the factors associated with the progression of this complication in elderly patients with type 2 diabetes. This retrospective study of a subgroup of patients registered with the Japanese Elderly Diabetes Intervention Trial included 621 Japanese patients with type 2 diabetes mellitus (age ≥ 65 years, 346 with normoalbuminuria, 190 with microalbuminuria and 85 with overt proteinuria). Multivariate Cox proportional hazard regression model with a backward stepwise procedure was applied to select factors with significant effects on worsening of nephropathy stage and the doubling of serum creatinine. During the follow up (median 52 months), 21% of patients progressed from normoalbuminuria and microalbuminuria to a worse nephropathy stage. Aging, female sex and high-density lipoprotein cholesterol were identified as independent and significant factors that worsen nephropathy stage. Also, 6.1% of patients showed doubling of serum creatinine during follow up. A positive history of cardiovascular disease, hyperuricemia and conventional therapy were identified as significant factors involved in the doubling of serum creatinine. The cumulative incidence of the doubling of serum creatinine was significantly lower in the intensive therapy group than the conventional therapy group (P = 0.016), although that of progression of nephropathy stage was similar in the two groups. We identified several factors associated with the progression of diabetic nephropathy in elderly patients with type 2 diabetes. The results suggest that multiple risk factor intervention seems important in preventing deterioration of renal dysfunction. © 2012 Japan Geriatrics Society.

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Patient safety education at Japanese medical schools: results of a nationwide survey

PubMed Central

2012-01-01

Background Patient safety education, including error prevention strategies and management of adverse events, has become a topic of worldwide concern. The importance of the patient safety is also recognized in Japan following two serious medical accidents in 1999. Furthermore, educational curriculum guideline revisions in 2008 by relevant the Ministry of Education includes patient safety as part of the core medical curriculum. However, little is known about the patient safety education in Japanese medical schools partly because a comprehensive study has not yet been conducted in this field. Therefore, we have conducted a nationwide survey in order to clarify the current status of patient safety education at medical schools in Japan. Results Response rate was 60.0% (n = 48/80). Ninety-eight-percent of respondents (n = 47/48) reported integration of patient safety education into their curricula. Thirty-nine percent reported devoting less than five hours to the topic. All schools that teach patient safety reported use of lecture based teaching methods while few used alternative methods, such as role-playing or in-hospital training. Topics related to medical error theory and legal ramifications of error are widely taught while practical topics related to error analysis such as root cause analysis are less often covered. Conclusions Based on responses to our survey, most Japanese medical schools have incorporated the topic of patient safety into their curricula. However, the number of hours devoted to the patient safety education is far from the sufficient level with forty percent of medical schools that devote five hours or less to it. In addition, most medical schools employ only the lecture based learning, lacking diversity in teaching methods. Although most medical schools cover basic error theory, error analysis is taught at fewer schools. We still need to make improvements to our medical safety curricula. We believe that this study has the implications for

Patient safety education at Japanese medical schools: results of a nationwide survey.

PubMed

Maeda, Shoichi; Kamishiraki, Etsuko; Starkey, Jay

2012-05-10

Patient safety education, including error prevention strategies and management of adverse events, has become a topic of worldwide concern. The importance of the patient safety is also recognized in Japan following two serious medical accidents in 1999. Furthermore, educational curriculum guideline revisions in 2008 by relevant the Ministry of Education includes patient safety as part of the core medical curriculum. However, little is known about the patient safety education in Japanese medical schools partly because a comprehensive study has not yet been conducted in this field. Therefore, we have conducted a nationwide survey in order to clarify the current status of patient safety education at medical schools in Japan. Response rate was 60.0% (n = 48/80). Ninety-eight-percent of respondents (n = 47/48) reported integration of patient safety education into their curricula. Thirty-nine percent reported devoting less than five hours to the topic. All schools that teach patient safety reported use of lecture based teaching methods while few used alternative methods, such as role-playing or in-hospital training. Topics related to medical error theory and legal ramifications of error are widely taught while practical topics related to error analysis such as root cause analysis are less often covered. Based on responses to our survey, most Japanese medical schools have incorporated the topic of patient safety into their curricula. However, the number of hours devoted to the patient safety education is far from the sufficient level with forty percent of medical schools that devote five hours or less to it. In addition, most medical schools employ only the lecture based learning, lacking diversity in teaching methods. Although most medical schools cover basic error theory, error analysis is taught at fewer schools. We still need to make improvements to our medical safety curricula. We believe that this study has the implications for the rest of the world as a

Japanese version of the Family Dermatology Life Quality Index: Translation and validation.

PubMed

Higaki, Yuko; Tanaka, Masaru; Futei, Yuko; Kamo, Toshiko; Basra, Mohammad Khurshid Azam; Finlay, Andrew Yule

2017-08-01

Skin conditions affect the quality of life (QoL) of patients and their family. To assess family members' QoL, a questionnaire uniquely designed for family members is necessary. We translated the Family Dermatology Life Quality Index (FDLQI), originally created and validated by Basra et al., into Japanese, and evaluated its reliability and validity. For psychometric evaluations, 150 dermatology patients and their family members were included. The Japanese version of the FDLQI showed high test-retest reliability (intraclass correlation coefficient = 0.95) and internal consistency reliability (Cronbach's alpha = 0.86). FDLQI scores significantly correlated with DLQI scores (r = 0.58, P < 0.01, Spearman's rho) and global question (GQ) which measured the patient's skin condition on a visual analog scale (r = 0.36, P < 0.01). Family members of patients with inflammatory skin diseases showed higher FDLQI scores than those with isolated lesions, but the difference was not statistically significant (P = 0.062, Mann-Whitney U-test). Responsiveness to change was demonstrated in a group in which the patient's skin condition was assessed as improved (n = 37, r = 0.46, P < 0.01) but not in that in which it became worse. The difference of the change between the two groups was statistically significant (P < 0.01). Additionally, the change in FDLQI scores and GQ were significantly correlated (r = 0.40, P < 0.01). Exploratory factor analysis suggested essential unidimensionality of the instrument. We showed acceptable validity and responsiveness of this Japanese version of FDLQI. Further clinical epidemiological studies are required to confirm this. © 2017 Japanese Dermatological Association.

Clinical Overview of Nephrogenic Diabetes Insipidus Based on a Nationwide Survey in Japan

PubMed Central

Fujimoto, Masanobu; Okada, Shin-ichi; Kawashima, Yuki; Nishimura, Rei; Miyahara, Naoki; Kawaba, Yasuo; Hanaki, Keiichi; Nanba, Eiji; Kondo, Yoshiaki; Igarashi, Takashi; Kanzaki, Susumu

2014-01-01

Background Nephrogenic diabetes insipidus (NDI) is a rare disease whose complications include polyuria, renal dysfunction, growth disorder and mental retardation. The details of NDI’s clinical course have been unclear. To address this uncertainty, we performed a large investigation of the clinical course of NDI in Japan. Methods Between December 2009 and March 2011, we provided a primary questionnaire to 26,282 members of the Japan Endocrine Society, the Japanese Urological Association, the Japanese Society for Pediatric Endocrinology, the Japanese Society for Pediatric Nephrology, the Japanese Society of Nephrology, the Japanese Society of Neurology and the Japanese Society of Pediatric Urology. In addition, we provided a secondary questionnaire to 121 members who reported experience with cases of NDI. We asked about patient’s age at onset, diagnosis, complications, effect of treatment and patient’s genotype. Results We enrolled 173 patients with NDI in our study. Of these NDI patients, 143 were congenital and 30 were acquired. Of the 173, 73 patients (42%) experienced urologic complications. Among the 143 with congenital NDI, 20 patients (14%) had mental retardation. Patients with NDI mainly received thiazide diuretics, and some patients responded to treatment with desmopressin acetate (DDAVP). Gene analyses were performed in 87 patients (61%) with congenital NDI, revealing that 65 patients had an arginine vasopressin receptor type 2 (AVPR2) gene mutation and that 8 patients (9.2%) had an aquaporin 2 (AQP2) gene mutation. Patients with the AVPR2 mutation (D85N) generally showed a mild phenotype, and we found that DDAVP was generally an effective treatment for NDI among these patients. Conclusion We suggest that adequate diagnosis and treatment are the most important factors for improving prognoses. We further suggest that gene analysis should be performed for optimal treatment selection and the early detection of NDI among siblings. PMID:25324589

Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

PubMed

Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Kameda, Hiroyuki; Tamura, Masahiro; Mihara, Hanako; Kaku, Kohei

2016-09-01

Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

A web-based incident reporting system and multidisciplinary collaborative projects for patient safety in a Japanese hospital

PubMed Central

Nakajima, K; Kurata, Y; Takeda, H

2005-01-01



Problem: When patient safety programs were mandated for Japanese health care institutions, a safety culture, a tool for collecting incident reports, an organizational arrangement for multidisciplinary collaboration, and interventional methods for improvement had to be established. Design: Observational study of effects of new patient safety programs. Setting: Osaka University Hospital, a large government-run teaching hospital. Strategy for change: A voluntary and anonymous web-based incident reporting system was introduced. For the new organizational structure a clinical risk management committee, a department of clinical quality management, and area clinical risk managers were established with their respective roles clearly defined to advance the plan-do-study-act cycle and to integrate efforts. For preventive action, alert procedures, staff education, ward rounds by peers, a system oriented approach for reducing errors, and various feedback channels were introduced. Effects of change: Continuous incident reporting by all hospital staff has been observed since the introduction of the new system. Several error inducing situations have been improved: wrong choice of drug in computer prescribing, maladministration of drugs due to a look-alike appearance or confusion about the manipulation of a medical device, and poor after hours service of the blood transfusion unit. Staff participation in educational seminars has been dramatically improved. Ward rounds have detected problematic procedures which needed to be dealt with. Lessons learnt: Patient safety programs based on a web-based incident reporting system, responsible persons, staff education, and a variety of feedback procedures can help promote a safety culture, multidisciplinary collaboration, and strong managerial leadership resulting in system oriented improvement. PMID:15805458

Clinical Features of Idiopathic Parotid Pain Triggered by the First Bite in Japanese Patients with Type 2 Diabetes: A Case Study of Nine Patients

PubMed Central

Hirotani, Hiroaki; Takahashi, Tetsu

2018-01-01

Objective First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. Study Design A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. Results All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0–10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1–10 min after meals in six patients. Conclusions IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different. PMID:29796314

Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat.

PubMed

Hasegawa, Daisuke; Yamato, Osamu; Kobayashi, Masanori; Fujita, Michio; Nakamura, Shinichiro; Takahashi, Kimimasa; Satoh, Hiroyuki; Shoda, Toru; Hayashi, Daisuke; Yamasaki, Masahiro; Maede, Yoshimitsu; Arai, Toshiro; Orima, Hiromitsu

2007-06-01

This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and subsequently died at about 7 months of age. Magnetic resonance imaging just before the death showed an enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2 hyperintensity in the white matter of the whole brain. Histological findings suggested a type of lysosomal storage disease. Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. The findings in the present cases provide useful information about GM2 gangliosidosis variant 0 in Japanese domestic cats.

Polycystic ovary syndrome: association of a C/T single nucleotide polymorphism at tyrosine kinase domain of insulin receptor gene with pathogenesis among lean Japanese women.

PubMed

Kashima, Katsunori; Yahata, Tetsuro; Fujita, Kazuyuki; Tanaka, Kenichi

2013-01-01

To assess whether the insulin receptor (INSR) gene contributes to genetic susceptibility to polycystic ovary syndrome (PCOS) in a Japanese population. We ex-amined the frequency of the His 1058 C/T single nucleotide polymorphism (SNP) found in exon 17 of the INSR gene in 61 Japanese PCOS patients and 99 Japanese healthy controls. In addition, we analyzed the association between the genotype of this SNP and the clinical phenotypes. The frequency of the C/C genotype was not significantly different between all PCOS patients (47.5%) and controls (35.4%). However, among the lean cases (body mass index < or = 20 kg/m2) the frequency of the C/C genotype was significantly increased (p < 0.05) in PCOS patients (65.0%) as compared with controls (36.6%). We concluded that the His 1058 C/T polymorphism at the tyrosine kinase domain of the INSR gene had a relationship to the pathogenesis of lean PCOS patients in a Japanese population.

Clinical outcomes of radiotherapy for esophageal cancer between 2004 and 2008: the second survey of the Japanese Radiation Oncology Study Group (JROSG).

PubMed

Nishimura, Yasumasa; Jingu, Keiichi; Itasaka, Satoshi; Negoro, Yoshiharu; Murakami, Yuji; Karasawa, Katsuyuki; Kawaguchi, Gen; Isohashi, Fumiaki; Kobayashi, Masao; Itoh, Yoshiyuki; Ariga, Takuro

2016-02-01

This second questionnaire-based survey was performed to determine the clinical results of definitive esophageal cancer treatment with radiotherapy (RT) or chemoradiotherapy (CRT) between 2004 and 2008. Clinical results of definitive RT for patients were collected from major Japanese institutions. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated with RT alone or CRT were included. For groups B and C, only those treated with CRT were included. In total, 990 patients (group A 259, group B 333, group C 398 patients) were included from 11 institutions. In group A, 199 patients (78 %) were treated with CRT, and 60 patients (23 %) received RT alone. In groups B and C, 420 patients (57 %) were treated with full-dose cisplatin/5-FU, and 181 patients (25 %) with low-dose protracted-infusion cisplatin/5-FU. The median and range of the 5-year overall survival rate were 73 % (40-94 %) for group A, 40 % (0-57 %) for group B, and 18 % (6-26 %) for group C, respectively. The 5-year overall survival rates were consistently good for five high-volume centers where more than 20 patients/year with esophageal cancer were treated definitively as compared with the remaining six medium-volume centers (5-15 patients/year). The median and range of the incidence of grade ≥3 late toxicities were 10 % and 6-22 %, respectively. A wide disparity in 5-year overall survival rates among the institutions was still apparent in the second survey for groups A and B.

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

PubMed

Sugishita, Mihoko; Imai, Tsuneo; Kikumori, Toyone; Mitsuma, Ayako; Shimokata, Tomoya; Shibata, Takashi; Morita, Sachi; Inada-Inoue, Megumi; Sawaki, Masataka; Hasegawa, Yoshinori; Ando, Yuichi

2016-03-01

Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses.

PubMed

Guy, Bruno; Guirakhoo, Farshad; Barban, Veronique; Higgs, Stephen; Monath, Thomas P; Lang, Jean

2010-01-08

Dengue viruses (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV) are major global health and growing medical problems. While a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (YFV), there is an urgent need for vaccines against dengue or West Nile diseases, and for improved vaccines against Japanese encephalitis. Live-attenuated chimeric viruses were constructed by replacing the genes coding for Premembrane (prM) and Envelope (E) proteins from YFV 17D vaccine strain with those of heterologous flaviviruses (ChimeriVax technology). This technology has been used to produce vaccine candidates for humans, for construction of a horse vaccine for West Nile fever, and as diagnostic reagents for dengue, Japanese encephalitis, West Nile and St. Louis encephalitis infections. This review focuses on human vaccines and their characterization from the early stages of research through to clinical development. Phenotypic and genetic properties and stability were examined, preclinical evaluation through in vitro or animal models, and clinical testing were carried out. Theoretical environmental concerns linked to the live and genetically modified nature of these vaccines have been carefully addressed. Results of the extensive characterizations are in accordance with the immunogenicity and excellent safety profile of the ChimeriVax-based vaccine candidates, and support their development towards large-scale efficacy trials and registration.

Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results).

PubMed

Imagawa, Tomoyuki; Nishikomori, Ryuta; Takada, Hidetoshi; Takeshita, Saoko; Patel, Neha; Kim, Dennis; Lheritier, Karine; Heike, Toshio; Hara, Toshiro; Yokota, Shumpei

2013-01-01

Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS. In this open-label study, 19 Japanese CAPS patients aged ≥2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight ≤ 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24. A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study. Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.

Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

PubMed

Watanabe, Yasuhiro; Beeldman, Emma; Raaphorst, Joost; Izumi, Yuishin; Yoshino, Hiide; Masuda, Michihito; Atsuta, Naoki; Ito, Satoru; Adachi, Tadashi; Adachi, Yoshiki; Yokota, Osamu; Oda, Masaya; Hanashima, Ritsuko; Ogino, Mieko; Ichikawa, Hiroo; Hasegawa, Kazuko; Kimura, Hideki; Shimizu, Toshio; Aiba, Ikuko; Yabe, Hayato; Kanba, Makoto; Kusumi, Kimiyoshi; Aoki, Tetsuya; Hiroe, Yu; Watanabe, Hirohisa; Nishiyama, Kazutoshi; Nomoto, Masahiro; Sobue, Gen; Nakashima, Kenji

2016-08-15

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

The cost effectiveness of rapid-acting insulin aspart compared with human insulin in type 2 diabetes patients: an analysis from the Japanese third-party payer perspective.

PubMed

Pollock, R F; Valentine, W J; Pilgaard, T; Nishimura, H

2011-01-01

The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo Nordisk A/S, Bagsvaerd, Denmark), a rapid-acting insulin analogue. The aim of the present analysis was to evaluate the cost effectiveness of insulin aspart versus regular human insulin from the perspective of a Japanese third-party healthcare payer. A discrete event-simulation model was developed in Microsoft Excel to assess the within-trial cost effectiveness and make longer-term clinical projections in patients treated with regular human insulin or insulin aspart. In addition to severe hypoglycaemia, the model captured myocardial and cerebral infarction events and percutaneous coronary intervention and coronary artery bypass graft procedures. Within-trial mortality, incidence of severe hypoglycaemia and cardiovascular event probabilities were derived from the annual rates observed during the trial period, while post-trial outcomes were calculated using the event rates from the trial, adjusted for increasing patient age. Event costs were accounted from the healthcare payer perspective and expressed in 2008 Japanese yen (JPY), while health-related quality of life (HRQoL) was captured using event and state utilities. Future costs and clinical benefits were discounted at 3% annually. Life expectancy, quality-adjusted life expectancy, cardiovascular event rates and costs were evaluated over 5- and 10-year time horizons and sensitivity analyses were performed to assess variability in model outcomes. Over 5 years of treatment, insulin aspart dominated human insulin both in incremental life expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart was associated with a small improvement in discounted life expectancy of 0.005 years (4.688 vs

Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Kanzaki, Sayaka; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2018-02-01

No studies have investigated the association between nocturia and depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia and depressive symptoms are common in patients with type 2 diabetes, we examined this association in Japanese patients with type 2 diabetes. We studied 762 Japanese patients with type 2 diabetes. A self-administered questionnaire was used to collect information about the variables under study. The subjects were divided into 3 groups according to their nocturnal micturition: 1) no nocturia; 2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more voids per night). Depressive symptoms were defined as being present when a subject had a Self-Rating Depression Scale score higher than 49. The prevalence values of mild nocturia, moderate to severe nocturia and depressive symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and moderate to severe nocturia were independently positively associated with depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to 3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and moderate to severe nocturia were independently associated with depressive symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respectively. In male patients, neither mild nocturia nor moderate to severe nocturia was significantly related to depressive symptoms. In Japanese female patients with type 2 diabetes, nocturia may be positively associated with depressive symptoms. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

Psychometric Properties of the Japanese Version of the STarT Back Tool in Patients with Low Back Pain.

PubMed

Matsudaira, Ko; Oka, Hiroyuki; Kikuchi, Norimasa; Haga, Yuri; Sawada, Takayuki; Tanaka, Sakae

2016-01-01

The STarT Back Tool uses prognostic indicators to classify patients with low back pain into three risk groups to guide early secondary prevention in primary care. The present study aimed to evaluate the psychometric properties of the Japanese version of the tool (STarT-J). An online survey was conducted among Japanese patients with low back pain aged 20-64 years. Reliability was assessed by examining the internal consistency of the overall and psychosocial subscales using Cronbach's alpha coefficients. Spearman's correlation coefficients were used to evaluate the concurrent validity between the STarT-J total score/psychosocial subscore and standard reference questionnaires. Discriminant validity was evaluated by calculating the area under the curves (AUCs) for the total and psychosocial subscale scores against standard reference cases. Known-groups validity was assessed by examining the relationship between low back pain-related disability and STarT-J scores. The analysis included data for 2000 Japanese patients with low back pain; the mean (standard deviation [SD]) age was 47.7 (9.3) years, and 54.1% were male. The mean (SD) STarT-J score was 2.2 (2.1). The Cronbach's alpha coefficient was 0.75 for the overall scale and 0.66 for the psychosocial subscale. Spearman's correlation coefficients ranged from 0.30 to 0.59, demonstrating moderate to strong concurrent validity. The AUCs for the total score ranged from 0.65 to 0.83, mostly demonstrating acceptable discriminative ability. For known-groups validity, participants with more somatic symptoms had higher total scores. Those in higher STarT-J risk groups had experienced more low back pain-related absences. The overall STarT-J scale was internally consistent and had acceptable concurrent, discriminant, and known-groups validity. The STarT-J can be used with Japanese patients with low back pain.

An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

PubMed

Takahashi, Michihiro; Takita, Yasushi; Goto, Taro; Ichikawa, Hironobu; Saito, Kazuhiko; Matsumoto, Hideo; Tanaka, Yasuo

2011-02-01

The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001). This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Clinical Improvement by Switching to an Integrase Strand Transfer Inhibitor in Hemophiliac Patients with HIV: The Japan Cohort Study of HIV Patients Infected through Blood Products.

PubMed

Kawado, Miyuki; Hashimoto, Shuji; Oka, Shin-Ichi; Fukutake, Katsuyuki; Higasa, Satoshi; Yatsuhashi, Hiroshi; Ogane, Miwa; Okamoto, Manabu; Shirasaka, Takuma

2017-01-01

This study aimed to determine improvement in HIV RNA levels and the CD4 cell count by switching to an antiretroviral regimen with an integrase strand transfer inhibitor (INSTI) in patients with HIV. This study was conducted on Japanese patients with HIV who were infected by blood products in the 1980s. Data were collected between 2007 and 2014. Data of 564 male hemophiliac patients with HIV from the Japan Cohort Study of HIV Patients Infected through Blood Products were available. Changes in antiretroviral regimen use, HIV RNA levels, and the CD4 cell count between 2007 and 2014 were examined. From 2007 to 2014, the proportion of use of a regimen with an INSTI increased from 0.0% to 41.0%. For patients with HIV who used a regimen, including an INSTI, the proportion of HIV RNA levels <50 copies/mL significantly increased from 58.3% in 2007 to 90.6% in 2014. Additionally, the median CD4 cell count significantly increased from 380/μL to 438/μL. There is a large effect of switching to an antiretroviral regimen with an INSTI for Japanese patients with HIV who are infected by blood products. This suggests that performing this switch in clinical practice will lead to favorable effects.

X-linked dominant protoporphyria: The first reported Japanese case.

PubMed

Ninomiya, Yukiko; Kokunai, Yasuhito; Tanizaki, Hideaki; Akasaka, Eijiro; Nakano, Hajime; Moriwaki, Shinichi

2016-04-01

A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. The patient's mother had no photosensitivity, however, lesions appearing slightly as small scars were found on the dorsum of her right hand; his elder sister and father showed no rash. The EP levels were elevated in samples from his mother and mildly elevated in those from his elder sister and father. To obtain a definitive diagnosis, genetic analyses were performed using samples from all family members, which revealed no mutations in the ferrochelatase-encoding gene (FECH), which is responsible for EPP. Instead, a pathological mutation of the 5-aminolevulinic acid synthase-encoding gene (ALAS2) was identified in samples from the patient, his mother and his elder sister, confirming a definitive diagnosis of X-linked dominant protoporphyria (XLDPP). This is the first Japanese family reported to have XLDPP, demonstrating evidence of the condition in Japan. In addition, because XLDPP is very similar to EPP in its clinical aspects and laboratory findings, a genetic analysis is required for the differential diagnosis. © 2015 Japanese Dermatological Association.

Exposure-Response Relationship for Ombitasvir and Paritaprevir/Ritonavir in Hepatitis C Virus Subgenotype 1b-Infected Japanese Patients in the Phase 3 Randomized GIFT-I Study.

PubMed

Gopalakrishnan, Sathej; Khatri, Amit; Mensing, Sven; Redman, Rebecca; Menon, Rajeev; Zha, Jiuhong

2016-04-01

The all-oral 2 direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir 25/150/100 mg once a day has been evaluated in hepatitis C virus subgenotype 1b-infected Japanese adults in the GIFT-I study. The aim of this analysis was to evaluate potential relationships between DAA exposures and laboratory abnormalities/adverse events of peripheral edema in patients in GIFT-I. The GIFT-I study consisted of a randomized, double-blind, placebo-controlled substudy in patients without cirrhosis and an open-label substudy in patients with compensated cirrhosis. Patients received ombitasvir/paritaprevir/ritonavir for 12 weeks. Exposure-response relationships between individual components of the ombitasvir/paritaprevir/ritonavir regimen and clinical parameters of interest were explored using pharmacokinetic and clinical data from patients in the study. Graphical analyses were performed. For events that occurred in at least 10 patients (total bilirubin elevation ≥grade 2 and peripheral edema ≥grade 1), multivariate logistic regression analyses were used to identify significant relationships between predictor variables (drug exposures) and response variables (probability of adverse events or laboratory abnormalities), with consideration for the effect of potential covariates and baseline status of response variables. Data from 321 noncirrhotic and 42 compensated cirrhotic patients were analyzed. There were 14 events of peripheral edema (10 at grade 1 and 4 at grade 2) in patients who received concomitant administration of calcium channel blockers and ombitasvir/paritaprevir/ritonavir. There was no apparent relationship between the incidences of peripheral edema and exposures of paritaprevir, ombitasvir, or ritonavir. There was a shallow relationship between total bilirubin elevation and exposures of paritaprevir which is an inhibitor of bilirubin transporter organic anion-transporting polypeptide 1B. Based on graphical analyses, exposures of paritaprevir

Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma

PubMed Central

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Ishizawa, Kenichi; Uike, Naokuni; Uchida, Toshiki; Suzuki, Tatsuya; Aoki, Tomohiro; Watanabe, Takashi; Maruyama, Dai; Yokoyama, Masahiro; Takubo, Takatoshi; Kagehara, Hideaki; Matsushima, Takafumi

2014-01-01

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin

Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

PubMed

Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

2016-02-01

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising <1%, 1 to 40%, or >40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

Sample Size Estimation for Alzheimer's Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging.

PubMed

Fujishima, Motonobu; Kawaguchi, Atsushi; Maikusa, Norihide; Kuwano, Ryozo; Iwatsubo, Takeshi; Matsuda, Hiroshi

2017-01-01

Little is known about the sample sizes required for clinical trials of Alzheimer's disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population. The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker. Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer's Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy. The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures. These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.

Dietary intake habits and the prevalence of nocturia in Japanese patients with type 2 diabetes mellitus.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2018-03-01

No reports have been published on the association between dietary intake habits and nocturia in the diabetes population. We therefore evaluated this issue among Japanese patients with diabetes mellitus. Study participants in the present study were 785 Japanese patients with type 2 diabetes mellitus. Self-administered questionnaires were used to assess each type of dietary intake habit. Vegetable intake habit was assessed by the following question: "Do you have vegetables or seaweed every day?" We used the following two outcomes: (i) nocturia: ≥2 voids per night; and (ii) severe nocturia: ≥3 voids per night. Adjustment was made for age, sex, body mass index, glycated hemoglobin, hypertension, dyslipidemia, smoking, drinking, exercise habit, stroke, ischemic artery disease, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy. The prevalence of nocturia, severe nocturia, and vegetable intake habit was 39.9%, 14.4% and 67.3%, respectively. After adjusting for confounding factors, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted odds ratios were 0.67 (95% confidence interval [CI] 0.48-0.94) and 0.46 (95% CI 0.30-0.71), respectively. Among male patients, vegetable intake habit was independently inversely associated with severe nocturia, but not nocturia: the adjusted OR was 0.51 (95% CI 0.29-0.88). Among female patients, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted ORs were 0.44 (95% CI 0.24-0.79) and 0.34 (95% CI 0.15-0.78), respectively. We found an inverse association between vegetable intake habit and nocturia in Japanese patients with type 2 diabetes mellitus. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

The results of a survey of physicians about the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 and its clinical use.

PubMed

Mogi, Masaki; Hasebe, Naoyuki; Horiuchi, Masatsugu; Shimamoto, Kazuaki; Umemura, Satoshi

2016-09-01

The current study investigated physicians' awareness and use of the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) and is based on the results of a survey performed by the Publicity and Advertisement Committee of JSH. A questionnaire was used to survey physicians' awareness of the JSH2014, their recommended target blood pressure for hypertensive patients with complications and their use of antihypertensive drugs. Physicians who downloaded a PDF version of JSH2014 during the 6 months after its publication (April-September 2014) were asked to complete an online questionnaire. Of the 7872 respondents, 91% were aware of the JSH and complied partially, mostly or completely with it in their practice. With reference to hypertensive patients, ∼70% of physicians who completed the questionnaire recommended a target blood pressure (BP) of 140/90 mm Hg for an office BP value, and 40% recommended 135/85 mm Hg for a home BP value. Physicians recommended target BP levels of 130/80 mm Hg for patients with diabetes or chronic kidney disease (50-63% of physician surveyed) and for elderly patients with diabetes or kidney disease (45-55% of respondents), whereas they recommended 140/90 mm Hg for elderly patients with low cardiovascular disease risk (56-60% of physician surveyed) and for patients with chronic-phase stroke (40-47% of respondents). The most commonly prescribed combination of antihypertensive drugs was angiotensin receptor blocker (ARB) with calcium channel blocker. In addition, physicians' first choice of drug for patients with diabetes or chronic kidney disease was most often ARB. Overall, the survey results showed that the new recommendations from the JSH2014 accurately reflect daily clinical practices for hypertension management used by Japanese physicians.

Worldwide Lineages of Clinical Pneumococci in a Japanese Teaching Hospital Identified by DiversiLab System.

PubMed

Kashiwaya, Kiyoshi; Saga, Tomoo; Ishii, Yoshikazu; Sakata, Ryuji; Iwata, Morihiro; Yoshizawa, Sadako; Chang, Bin; Ohnishi, Makoto; Tateda, Kazuhiro

2016-06-01

Pneumococcal Molecular Epidemiology Network (PMEN) clones are representatives of worldwide-spreading pathogens. DiversiLab system, a repetitive PCR system, has been proposed as a less labor-and time-intensive genotyping platform alternative to conventional methods. However, the utility and analysis parameters of DiversiLab for identifying worldwide lineages was not established. To evaluate and optimize the performance of DiversiLab for identifying worldwide pneumococcal lineages, we examined 245 consecutive isolates of clinical Streptococcus pneumoniae from all age-group patients at a teaching hospital in Japan. The capsular swelling reaction of all isolates yielded 24 different serotypes. Intensive visual observation (VO) of DiversiLab band pattern difference divided all isolates into 73 clusters. Multilocus sequence typing (MLST) of representative 73 isolates from each VO cluster yielded 51 different STs. Among them, PMEN-related lineages accounted for 63% (46/73). Although the serotype of PMEN-related isolates was identical to that of the original PMEN clone in 70% (32/46), CC156-related PMEN lineages, namely Greece(6B)-22 and Colombia(23F)-26, harbored various capsular types discordant to the original PMEN clones. Regarding automated analysis, genotyping by extended Jaccard (XJ) with a 75% similarity index cutoff (SIC) showed the highest correlation with serotyping (adjusted Rand's coefficient, 0.528). Elevating the SIC for XJ to 85% increased the discriminatory power sufficient for distinguishing two major PMEN-related isolates of Taiwan(19F)-14 and Netherlands(3)-31. These results demonstrated a potential utility of DiversiLab for identifying worldwide lineage of pneumococcus. An optimized parameters of automated analysis should be useful especially for comparison for reference strains by "identification" function of DiversiLab. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd

Diseases affecting patients returning from abroad: Experience of a travel clinic in Japan from 2004 to 2014.

PubMed

Yoshimura, Yukihiro; Miyata, Nobuyuki; Miyajima, Makiko; Sakamoto, Yohei; Amano, Yuichiro; Tachikawa, Natsuo

2017-01-01

The number of patients returning from or staying abroad is likely to increase in the future. We performed a retrospective study of patients returning from abroad in our travel clinic in Japan. All patients presenting within 6 months of traveling abroad between 2004 and 2014 were included in the present study. A total of 2374 (mean age, 35 years) patients were seen by doctors specializing in treating infectious diseases. Of these, 918 were females and 87 of them lived abroad. Diagnoses and exposure regions were recorded for all patients. The most frequent region visited before attending our clinic was Southeast Asia (n = 1050, 44%), with a median duration for staying abroad of 8 days. The major purposes for overseas travel were tourism (n = 1302, 55%) and business (n = 684, 29%). Of the 2399 individual diagnoses made, the most frequent were diseases of the gastrointestinal system (n = 1083, 45%), skin and soft tissue (n = 440, 18%), systemic febrile disease without specific systems (419, 18%), and the respiratory system (353, 15%). The relative incidences of specific diseases changed drastically due to significant disease outbreaks, such as pandemic influenza in 2009. Exposure regions remained relatively constant throughout the study period, except for Japan. Vaccine-preventable diseases accounted for 5.3% of all the diseases, and 402 (26%) patients received pre-travel consultation and prophylaxis with vaccines and/or anti-malarial drug. We should make an effort to make more people notice the risk of travel and properly perform prophylaxis. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1.

PubMed

Nakanishi, Hiroshi; Ohtsubo, Masafumi; Iwasaki, Satoshi; Hotta, Yoshihiro; Takizawa, Yoshinori; Hosono, Katsuhiro; Mizuta, Kunihiro; Mineta, Hiroyuki; Minoshima, Shinsei

2010-12-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 1 (USH1), the second common type of USH, is frequently caused by MYO7A and CDH23 mutations, accounting for 70-80% of the cases among various ethnicities, including Caucasians, Africans and Asians. However, there have been no reports of mutation analysis for any responsible genes for USH1 in Japanese patients. This study describes the first mutation analysis of MYO7A and CDH23 in Japanese USH1 patients. Five mutations (three in MYO7A and two in CDH23) were identified in four of five unrelated patients. Of these mutations, two were novel. One of them, p.Tyr1942SerfsX23 in CDH23, was a large deletion causing the loss of 3 exons. This is the first large deletion to be found in CDH23. The incidence of the MYO7A and CDH23 mutations in the study population was 80%, which is consistent with previous findings. Therefore, mutation screening for these genes is expected to be a highly sensitive method for diagnosing USH1 among the Japanese.

Panitumumab in Japanese Patients with Unresectable Colorectal Cancer: A Post-marketing Surveillance Study of 3085 Patients†

PubMed Central

Boku, Narikazu; Sugihara, Kenichi; Kitagawa, Yuko; Hatake, Kiyohiko; Gemma, Akihiko; Yamazaki, Naoya; Muro, Kei; Hamaguchi, Tetsuya; Yoshino, Takayuki; Yana, Ikuo; Ueno, Hiroshi; Ohtsu, Atsushi

2014-01-01

Objective Panitumumab was approved in Japan in April 2010 for the treatment of Kirsten rat sarcoma-2 virus oncogene wild-type unresectable and recurrent colorectal cancer. We conducted a post-marketing surveillance study to evaluate the safety and effectiveness of panitumumab. Methods After panitumumab was commercially available in Japan, all patients to be treated with panitumumab were enrolled. Data on baseline characteristics, treatment outcome, and incidence and severity of adverse drug reactions were collected. Results In total, 3091 patients were registered. In the safety analysis set (n = 3085), panitumumab was administered as monotherapy (40.7%) or combination therapy (59.4%). The median treatment duration was 113 days (range: 1–559 days), and 451 (14.6%) patients received panitumumab for ≥10 months. The overall incidence rate of adverse drug reactions was 84.1%, and the most common adverse drug reaction was skin disorders (78.4%). The incidence rates (all grades) of interstitial lung disease, infusion reaction, electrolyte abnormalities and cardiac disorders were 1.3% (mortality rate: 0.6%), 1.5, 19.3 and 0.2%, respectively. The median survival time of patients treated with panitumumab monotherapy as the third-line, or later, therapy was 10.3 months. Conclusion This post-marketing survey in clinical practice confirmed the safety and effectiveness of panitumumab. The benefit/risk balance for panitumumab in Japanese patients with unresectable colorectal cancer remains favorable. PMID:24526771

One-year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases.

PubMed

Yagami, Akiko; Furue, Masutaka; Togawa, Michinori; Saito, Akihiro; Hide, Michihiro

2017-04-01