Failure In Japan Research Articles

JS1-4 - Drug Therapy of Heart Failure in Japan

Heart failure syndrome (HF) is one of the major public health concerns, since the number of aged people who are susceptible for HF are increasing and donor supply for cardiac transplantation is limited in Japan. Several clinical trials have established that beta-adrenergic receptor blockers are most useful in prolonging life expectancy in general population of HF in addition to renin-angiotensin system blockade. However, several problems remain to be solved. HF is accompanied by multiple comorbidities, especially in elderly patients. Use of evidence-based medicines is limited in such patients. Epidemiological survey has shown that there are considerable differences in general practices by the countries. In addition, couples of novel pharmacologic therapies such as ivabradine and angiotensin-neprilysin inhibitor remain to be approved in our country. Finally, therapeutic strategy for HF with predominantly diastolic dysfunction is another concern. HF with preserved ejection fraction is the most important issue as a new economic burden of coming era. Renin-angiotensin system blockade appears to be promising in patients with HF due to predominantly diastolic dysfunction, which is a common setting in elderly people.

Design of a nationwide survey on palliative care for end-stage heart failure in Japan

BackgroundThe term palliative care has historically been associated with support for individuals with advanced incurable cancer, so cardiologists and cardiac nurses may be unfamiliar with its principles and practice. However, palliative care is now a part of end-stage heart failure management. We conducted the first nationwide survey to investigate the status of palliative care for heart failure in Japan. Methods and resultsA self-reported questionnaire was mailed to all Japanese Circulation Society – authorized cardiology training hospitals (n=1004) in August 2016. The response deadline was December 2016. The survey focused on the following topics: basic information about the facility and multidisciplinary team, patient symptoms for palliative care, positive outcomes after providing palliative care, drug therapy as palliative care for patients with heart failure, advance care planning with patients and their families, and impediments to providing palliative care to patients with heart failure. The results of the survey will be reported in detail elsewhere. ConclusionsCurrent guidelines on palliative care do not specifically address what team members should be involved, what drugs should be used, or when palliative care should be started. This survey collected information to improve the quality of palliative care and provide more specialized palliative care within the limits of resources.

P1490Age-related differences in characteristics and management of acute decompensated heart failure in Japan: insights from the kyoto congestive heart failure registry

P1490Age-related differences in characteristics and management of acute decompensated heart failure in Japan: insights from the kyoto congestive heart failure registry

P3369Impact of optimal medical therapy on one-year outcomes in acute decompensated heart failure in Japan

P3369Impact of optimal medical therapy on one-year outcomes in acute decompensated heart failure in Japan

Efficacy of the endometrial receptivity array for repeated implantation failure in Japan: A retrospective, two-centers study.

AimThis study aimed to assess the efficacy of the endometrial receptivity array (ERA) as a diagnostic tool and the impact of personalized embryo transfer (pET) for the treatment of patients with recurrent implantation failure (RIF) in Japan.MethodsFifty patients with a history of RIF with frozen‐thawed blastocyst transfers were recruited from July, 2015 to April, 2016. Endometrial sampling for the ERA and histological dating and a pET according to the ERA were performed. The receptive (R) or non‐receptive (NR) status of the endometrium as a result of the first ERA, endometrial dating, and pregnancy rates after the pET were analyzed.ResultsOf the patients with RIF, 12 (24%) were NR. Among them, eight (66.7%) were prereceptive. A clinical follow‐up was possible in 44 patients who underwent the pET. The pregnancy rates were 58.8% per patient and 35.3% per first pET in the R patients and 50.0% per patient and 50.0% per first pET in the NR patients. Discrepancies between the ERA results and histological dating were seen more in the NR patients than in the R patients.ConclusionsFor patients with unexplained RIF, there is a significance in searching for their personal window of implantation (WOI) using the ERA, considering the percentage of those who were NR and the pregnancy rates that resulted from the pET. By transferring euploid embryos in a personal WOI, much better pregnancy rates are expected.

Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.

Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice. The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14days after cisplatin injection (16mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured. ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8days after cisplatin injection. ANP significantly increased serum G-CSF levels 1day after cisplatin injection. ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.

Trends and determinant factors in the use of cardiac resynchronization therapy devices in Japan: Analysis of the Japan cardiac device treatment registry database

BackgroundThe choice of cardiac resynchronization therapy device, with (CRT-D) or without (CRT-P) a defibrillator, in patients with heart failure largely depends on the physician׳s discretion, because it has not been established which subjects benefit most from a defibrillator. MethodsWe examined the annual trend of CRT device implantations between 2006 and 2014, and evaluated the factors related to the device selection (CRT-D or CRT-P) for primary prevention of sudden cardiac death in patients with heart failure by analyzing the Japan Cardiac Device Treatment Registry (JCDTR) database from January 2011 and August 2015 (CRT-D, n=2714; CRT-P, n=555). ResultsThe proportion of CRT-D implantations for primary prevention among all the CRT-D recipients was more than 70% during the study period. The number of CRT-D implantations for primary prevention reached a maximum in 2011 and decreased gradually between 2011 and 2014, whereas CRT-P implantations increased year by year until 2011 and remained unchanged in recent years. Multivariate analysis identified age (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.90–0.95, P<0.0001), male sex (OR 1.99, 95% CI 1.28–3.11, P<0.005), reduced left ventricular ejection fraction (LVEF) (OR 0.96, 95% CI 0.94–0.98, P<0.0001), and non-sustained ventricular tachycardia (NSVT) (OR 2.85, 95% CI 1.87–4.35, P<0.0001) as independent factors favoring the choice of CRT-D. ConclusionsYounger age, male sex, reduced LVEF, and a history of NSVT were independently associated with the choice of CRT-D for primary prevention of sudden cardiac death in patients with heart failure in Japan.

Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force.

Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β2-integrin focal bond formation. ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ∼40% increase in neutrophil viscosity and a reduction in the adhesive footprint. A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment.

Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.

In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.

Distribution of core hospitals for patients with fulminant hepatitis and late onset hepatic failure in Japan.

Distribution of core hospitals for patients with fulminant hepatitis and late onset hepatic failure in Japan.

An assessment of the material point method for modelling large scale run-out processes in landslides

This paper demonstrates the predictive capabilities of a numerical model based on continuum mechanics for the simulation of run-out processes during landslides. It assesses a particle-based method that takes advantage of a double Lagrangian-Eulerian discretization and known as the material point method (MPM). Attention is given to the post-failure behaviour and, in particular, to the computation of important quantities such as run-out distance, maximum velocity and energy release. The MPM is a step forward in computational solid mechanics and has the potential to simulate large deformations such as those occurring during landslides. A validation is conducted based on simulations of two case studies of different scales, namely the Tokai-Hokuriku expressway failure in Japan and the Vajont landslide in Italy. The results show a very good agreement with field and other numerical observations.

Outcomes in children with advanced heart failure in Japan: importance of mechanical circulatory support.

The Japanese organ transplant law was revised in July 2010 in order to enable children aged <15years to donate organs. However, the waiting time for orthotopic heart transplantation (HTx) is as long as 636days in children due to a shortage of organ donors. Ventricular assist devices (VADs) have been widely used as a bridge to transplantation in Western countries, whereas experience with VADs is limited in Japan due to a lack of device availability for small children. This study aimed to clarify the clinical profiles and outcomes of children with advanced heart failure in Japan and to investigate the importance of mechanical circulatory support (MCS), VADs, and extracorporeal membrane oxygenation (ECMO) in children. A retrospective chart review of patients with advanced heart failure who were eligible for HTx between January 2006 and May 2015 was performed at the Department of Pediatric Cardiology, Tokyo Woman's Medical University, Japan. Patients were divided into two groups based on need for MCS. Clinical data pre- and post-revision of the Japanese organ transplant law were compared. Preoperative clinical conditions were evaluated based on Interagency Registry for Mechanically Circulatory Support (INTERMACS) profiles. Twenty-two patients were included in the study, 12 of whom required MCS. VADs were implanted in nine patients and ECMO was needed in seven patients. Of the MCS group, 5 deaths occurred in patients with a preoperative INTERMACS profile-1. High total bilirubin was found to be associated with mortality by multivariate logistic regression analysis (OR 7.8, p=0.02). Wait list mortality was 32% and no difference in clinical profiles pre- and post-revision of the Japanese organ transplant law was observed. Approximately 55% of pediatric patients with advanced heart failure required MCS support. Preoperative conditions such as INTERMACS profile-1 and high total bilirubin were associated with poor outcomes. The Japanese organ transplant law revision had no significant influence on patient profiles or outcomes.

Revisions made for crizotinib-related cardiac failure in Japan

Revisions made for crizotinib-related cardiac failure in Japan

Clinical Profiles and Prognostic Factors in the Elderly Patients with Heart Failure in Japan - A Report from the CHART-2 Study

Prognostic Impacts and Temporal Changes of Post-Traumatic Stress Disorder after the Great East Japan Earthquake in Patients with Heart Failure A Report from the CHART-2 Study Takeo Onose, Yasuhiko Sakata, Masanobu Miura, Soichiro Tadaki, Ryoichi Ushigome, Takeshi Yamauchi, Kenjiro Sato, Kanako Tsuji, Ruri Abe, Kotaro Nochioka, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa; Tohoku University Graduate School of Medicine, Sendai, Japan

The economic issue of vascular access within the Japanese medical reimbursement system.

We analyzed the current health economics of vascular access (VA) procedures in Japan. Results showed that the yearly VA-related medical expenses were as high as JPY20 billion and accounted for 1.4% of the total healthcare cost for chronic renal failure. The United States Renal Data System (USRDS) statistics showed that in the USA the yearly VA-related medical expenses accounted for 1.2% of the total medical cost for chronic renal failure, indicating that the costs did not differ much between the two countries. Moreover, percutaneous transluminal angioplasty (PTA) accounts for approximately 60% of VA procedures performed in Japan, and this ratio is increasing every year. Due to the aging of society and longer treatment periods, it is thought that PTA will become a significant procedure for the treatment of chronic renal failure in Japan.

Treatment of acute liver failure in Japan

Treatment of acute liver failure in Japan

On‐line hemodiafiltration or high‐flow continuous hemodiafiltration is one of the most effective artificial liver support devices for acute liver failure in Japan

On‐line hemodiafiltration or high‐flow continuous hemodiafiltration is one of the most effective artificial liver support devices for acute liver failure in Japan

Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure in Japan -- report from the CHART Studies.

Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure (HF) remain to be elucidated in Japan. From the Chronic Heart Failure Analysis and Registry in the Tohoku District-1 (CHART-1; 2000-2005, n=1,278) and CHART-2 (2006-present, n=10,219) Studies, we enrolled 1,006 and 3,676 consecutive symptomatic stage C/D HF patients, respectively. As compared with the patients in the CHART-1 Study, those in the CHART-2 Study had similar age and sex prevalence, and were characterized by lower brain natriuretic peptide, higher prevalence of preserved left ventricular ejection fraction (LVEF) and higher prevalence of hypertension, diabetes mellitus and ischemic heart disease (IHD), particularly IHD with LVEF ≥50%. From CHART-1 to CHART-2, use of renin-angiotensin system inhibitors, β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was decreased. Three-year incidences of all-cause death (24 vs. 15%; adjusted hazard ratio [adjHR], 0.73; P<0.001), cardiovascular death (17 vs. 7%; adjHR, 0.38; P<0.001) and hospitalization for HF (30 vs. 17%; adjHR, 0.51; P<0.001) were all significantly decreased from CHART-1 to CHART-2. In the CHART-2 Study, use of β-blockers was associated with improved prognosis in patients with LVEF <50%, while that of statins was associated with improved prognosis in those with LVEF ≥50%. Along with implementation of evidence-based medications, the prognosis of HF patients has been improved in Japan. ( clinicaltrials.gov identifier: NCT00418041)

Central Morphology Review of Childhood Bone Marrow Failure in Japan

In the diagnosis of childhood bone marrow failure (BMF), differentiating aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (MDS) is challenging. In addition, inherited BMF (IBMF) should be excluded from acquired BMF. The 2008 WHO classification has proposed a provisional entitiy, “refractory cytopenia of childhood (RCC)”. The spectrum of patients with RCC is wide, ranging from patients with severe hypocellular bone marrow (BM) and mild dysplasia to those with normocellular BM and distinct dysplasia meeting the criteria for refractory cytopenia with multilineage dysplasia (RCMD) in adults. Currently, it is recommended that children who meet the criteria for RCMD should be considered as RCC in the WHO classification until the number of lineages involved have been fully evaluated with regard to their relative importance as prognostic factors in childhood MDS.To enable diagnosis based on the WHO classification, the Japanese Society of Pediatric Hematology and Oncology in February 2009 established a central review system of BM morphology, including peripheral blood (PB) and BM smears and specimens from trephine biopsies in childhood BMF. PB and BM smears were reviewed by two pediatric hematologists, and the specimens from BM trephine biopsies were reviewed by a pathologist. In addition, the telomere length of lymphocytes and paroxysmal nocturnal hemoglobinuria (PNH) clones in PB were measured by flowcytometry for patients with BMF. RCC is defined as persistent cytopenia with <2% and <5% blasts in PB and BM, respectively. BM aspirate smears show dysplastic changes in >2 cell lineages or >10% within one cell lineage. On the other hand, the criteria of RCMD in adult MDS is defined as persistent cytopenia with <1% and <5% blasts in PB and BM, respectively. BM smears show >10% dysplastic changes in >2 cell lineages. We introduced the RCMD criteria in this central review.From February 2009 to October 2013, 1,000 cases including 536 males and 464 females were prospectively reviewed. The median age was six years (range, 0–39 years). Of the 1,000 cases, 575 were classified as BMF, and of them, 137 were classified as AA, 236 as RCC, 103 as RCMD, 38 as hepatitis-related BMF, 3 as PNH and 58 as IBMF. Of the 58 cases with IBMF, 21 were diagnosed as Fanconi anemia, 12 as Shwachman–Diamond syndrome, and 8 as dyskeratosis congenita. Seventeen patients suspected of IBMF were undiagnosed. In 97 advanced cases of MDS, 24 were classified as refractory anemia with excess blasts (RAEB), 6 as secondary MDS, and 21 as therapy-related MDS. To determine the clinical differences among AA, RCC, and RCMD, we compared laboratory and clinical data for 476 patients classified as AA, RCC, and RCMD. Median ages in the AA, RCC, and RCMD groups were 9, 8, and 7 years, respectively (p = 0.007). The male/female ratio in AA, RCC, and RCMD groups was 1.1, 1.2, and 3.6, respectively (p = 0.034). When patients were classified according to the disease severity criteria for AA, 78% of the patients with AA had very severe or severe disease, whereas only 38% of the patients with RCC and 28% of the patients with RCMD had very severe or severe disease (p < 0.001). Chromosomal abnormalities were detected in two patients (1%) with AA (trisomy 8), 10 patients (4%) with RCC (monosomy 7, n = 2; trisomy 8, n = 6; other, n = 2), and 12 patients (12%) with RCMD (monosomy 7, n = 5; trisomy 8, n = 2; other, n = 5) (p = 0.001). Out of the 476 patients, 67 (AA, n = 32; RCC, n = 32; RCMD, n = 3) were administered IST with rabbit antithymocyte globulin (ATG) and cyclosporine. After 6 months, the response rate to IST was not significantly different among the three groups; AA, 41%; RCC, 47%; RCMD, 100% (p = 0.142).In conclusion, the entity of RCMD should be applied to childhood MDS because patients with RCMD exhibited a significantly high frequency of chromosomal abnormalities at the time of diagnosis. To definitively determine whether these three diseases are different entities, it would be necessary to prospectively compare the clinical outcomes and biological findings in a larger number of patients with AA, RCC, and RCMD. DisclosuresNo relevant conflicts of interest to declare.

To globalise or not to globalise? ‘Inward-looking youth’ as scapegoats for Japan's failure to secure and cultivate ‘global human resources’

In Japan in recent years, there has been much discussion of the need for global human resources alongside criticism of Japanese youth as having an ‘inward-looking’ (uchimuki) orientation. Drawing out the contradictions apparent in a youth apparently reluctant to leave Japan and companies, universitiesand government seemingly desperate to nurture and attract global talent, this paper frames the uchimuki discourse as a cover for an insular Japan and its failure to attract and foster ‘global human resources’.As such, the two discourses shed a great deal of light on Japan's complex relationship with globalisation.