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Chisato Izumi,1 Rei Matsuyama,2 Kaoru Yamabe,2 Kosuke Iwasaki,3 Tomomi Takeshima,3 Shannon ME Murphy,4 Lida Teng,5 Ataru Igarashi5,6 1Division of Heart Failure, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; 2Market Access, Edwards Lifesciences Limited, Tokyo, Japan; 3Milliman Inc., Tokyo, Japan; 4Edwards Lifesciences Corporation, Irvine, CA, USA; 5Department of Health Economic and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 6Unit of Public Health and Preventive Medicine Yokohama City University School of Medicine, Kanagawa, JapanCorrespondence: Ataru Igarashi, Department of Health Economic and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan, Tel +81 3 5841 4828, Email atarui1@mac.com Kaoru Yamabe, Market Access, Edwards Lifesciences Limited, Nittochi Nishi-shinjuku Building, 6-10-1, Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81 80 4442 0883, Fax +81 3 6894 0034, Email kaoru_yamabe@edwards.comPurpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis.Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost.Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95– 1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03– 1.07]; p< 0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25– 1.32]; p< 0.001).Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.Graphical Abstract: Keywords: length of stay, medical costs, mortality, etiology, hospital claims, medical data vision

Kaoru Yamabe,1 Ryan Liebert,2 Natalia Flores,2 Chris L Pashos3 1Healthcare Policy and Access, Takeda Pharmaceutical Company Limited, Nihonbashi, Chuouku, Tokyo 103-8668, Japan; 2Health Outcomes Research, Kantar Health, New York, NY 10010, USA; 3Global Outcomes and Epidemiology Research, Data Sciences Institute, Takeda Pharmaceuticals International Inc., Cambridge, MA, 02139, USA Purpose: Previous Japanese studies have not compared health-related quality of life (HRQoL), work productivity and activity impairment, health care resource utilization (HRU), and costs in inflammatory bowel disease (IBD) patients with non-IBD controls, leading to insufficient evidence regarding IBD’s true burden. The aim of this study was to examine the impact of IBD on patient-reported outcomes and costs among Japanese adults (≥18 years). Patients and methods: This retrospective cross-sectional study used data from the 2012–2014 Japan National Health and Wellness Survey (N=83,505). HRQoL (SF-36v2), work productivity and activity impairment (work productivity and activity impairment-General Health Questionnaire), HRU, and annual costs were compared between respondents with IBD (n=441) and non-IBD controls (n=82,944), and within IBD subtypes (Crohn’s disease [CD] and ulcerative colitis [UC]) using chi-square and ANOVA tests. Results: Mental Component Summary (MCS), Physical Component Summary (PCS), and health state utility (Short-Form-6 Dimensions [SF-6D]) scores were significantly lower in IBD respondents than in controls (differences of 2.2 points, 2.6 points, and 0.041 points, respectively; all P

Kaoru Yamabe,1 Ryan Liebert,2 Natalia Flores,2 Chris L Pashos3 1Healthcare Policy and Access, Takeda Pharmaceutical Company Limited, Nihonbashi, Chuouku, Tokyo 103-8668, Japan; 2Health Outcomes Research, Kantar Health, New York, NY 10010, USA; 3Global Outcomes & Epidemiology Research, Data Sciences Institute, Takeda Pharmaceuticals International, Inc., Cambridge, MA 02139, USA Purpose: Depression is associated with substantial health and economic burden. This study examined the impact of diagnosed and undiagnosed depression on health-related outcomes and costs among Japanese adults. Methods: A retrospective, observational study was conducted using 2012–2014 Japan National Health and Wellness Survey (N=83,504) data. Differences between respondents diagnosed with depression (n=2,843) and undiagnosed with depression (weighted n=2,717) and controls without depression (weighted n=2,801) in health-related quality of life, impairment to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire), health care resource utilization, and annual costs were evaluated. Propensity score weighting and weighted generalized linear models were used to compare groups on the outcome variables, after adjusting for covariates. Results: Overall, respondents with undiagnosed depression had significantly better outcomes than those diagnosed with depression, but significantly worse outcomes than controls (for all, P

Kaoru Yamabe,1 Marco D DiBonaventura,2 Chris L Pashos3 1Healthcare Policy and Access, Takeda Pharmaceutical Company Limited, Chuouku, Tokyo 103-8668, Japan; 2Health Outcomes, Kantar Health, New York, NY 10010, USA; 3Global Outcomes and Epidemiology Research. Data Sciences Institute, Takeda Pharmaceutical International, Cambridge, MA 02139, USA Purpose: Multiple sclerosis (MS) imposes a huge burden on patients. This study examined the relationship between MS and health-related and economic burden in Japan; secondarily, health status was compared across patients with MS in Japan, US, and five European Union (5EU) countries (France, Germany, Italy, Spain, and UK).Methods: A retrospective cross-sectional study was conducted using self-reported data from 2009 to 2014 Japan National Health and Wellness Survey (n=145,759). Health status, work productivity loss, activity impairment, health care resource utilization, and annual costs associated with MS (n=85) were compared with controls without MS (n=145,674). Propensity score matching and multivariable linear regressions determined the effect of MS after controlling for confounders. Health status in Japan was also compared with that of 5EU (n=62) and US (n=67) patients with MS.Results: Patients with MS in Japan reported significantly worse health status via mental component summary score (MCS; 40.1 vs 45.8) and physical component summary score (PCS; 41.4 vs 51.2) and health state utility scores (0.63 vs 0.74; all P

Kaoru Yamabe Healthcare Policy and Access, Takeda Pharmaceutical Company Limited, Chuou-ku, Tokyo, JapanThis series presents articles using data collected from the National Health and Wellness Survey1 in Japan to assess the burden of inflammatory bowel disease (IBD), multiple sclerosis (MS), and depression using a common methodology involving cases vs. controls and patient-reported outcome measures (PROMs).

A combinatorial method is used to fabricate work function (WF) tuned Pt-W alloy films, which are used as metal electrodes for Hf[O.sub.2]/Si[O.sub.2]/Si capacitors. The results have shown that the control of bonding states at the metal/Hf[O.sub.2] interfaces on an atomic scale is necessary for the realization of a combination of metal and high-[kappa] dielectric films in metal-oxide-semiconductor devices.

Vacancy-impurity complexes in polycrystalline Si (poly-Si) used as gate electrodes of HfSiON-based metal-oxide-semiconductor field-effect transistor (MOSFET) are detected by using monoenergetic positron beams. The results have suggested that suppression of the oxygen diffusion from high-k gate dielectrics into gate electrodes are necessary for MOSFETs and the positron annihilation parameter is sensitive to change in the vacancy-type defects in poly-Si used as gate electrodes.

The impact of nitridation on open volumes in thin HfSiO(sub x) films fabricated on Si substrates by atomic layer deposition is studied using monoenergetic positron beams. It is found that the size of open volumes increased with increasing nitrogen concentration in HfSiO(sub x) and the change in the size of open volumes is attributed to the trapping of nitrogen by open volumes, and an incorporation of nitrogen into the amorphous matrix of HfSiO(sub x) during postnitridation annealing (PNA).

The thin Hf(sub 0.6)Si(sub 0.4)O(sub x) and Hf(sub 0.3)Al(sub 0.7)O(sub x) films, which are fabricated by metal-organic chemical-vapor deposition and atomic-layer-deposition techniques, are characterized using monoenergetic positron beams. The results show that positron annihilation parameter is sensitive to change in the matrix structure of amorphous high-k materials and can be used to determine process parameters for the fabrication of high-k gate dielectrics.

The effect of annealing on open volumes in strained SiN films deposited on Si by plasma enhanced chemical vapor deposition was studied using monoenergetic positron beams. For compressive SiN, the stress was reduced by postdeposition annealing; this effect was attributed to the relaxation of matrix structures accompanied by an expansion of small open spaces intrinsically existing in the matrix and the introduction of large open volumes. For tensile SiN, although annealing tends to decrease the concentration of large open volumes, the size of the small open spaces and the film stress were almost constant up to 1000 °C annealing. This was attributed to the network structure related to the open spaces remaining stable even at 1000 °C annealing, and this mainly determines the stress in the tensile film. [ABSTRACT FROM AUTHOR]

We have applied a combinatorial technique to fabricate work function (WF) tuned Pt-W alloy films and used the films as metal electrodes for HfO2/SiO2/Si capacitors. As the ratio, RPt, of Pt to W changes from 0 to 1, the WF value varies continuously from 4.7 to 5.5 eV. This tunability enables us to systematically investigate the effect of WF variation on electrical properties. After a forming gas annealing process, the values of flatband voltage (Vfb) from capacitance-voltage properties are almost constant, regardless of the WF variation, because of oxygen vacancy formation that results in Fermi level pinning. On additional oxidizing gas annealing (OGA), the effect of WF value on Vfb becomes dominant. However, the difference in Vfb between W and Pt is 0.34 V, which is much smaller than the observed WF difference of 0.8 eV. We attribute this phenomenon to the lowering of the effective WF due to an electric dipole, induced by oxygen vacancy formation at the metal/HfO2 interface. Moreover, a decrease in Vfb in W-rich regions was observed following the OGA, suggesting the formation of a W-O bond at the interface. These results clearly indicate that the control of bonding states at the metal/HfO2 interfaces on an atomic scale is essential for the realization of a combination of metal and high-k dielectric films in future complementary metal-oxide-semiconductor devices. [ABSTRACT FROM AUTHOR]

The impact of TiN deposition on thin HfO2 films formed on Si substrates was studied using x-ray photoelectron spectroscopy and a monoenergetic positron beam. For the predeposition sample, the positrons implanted into Si were found to diffuse toward the HfO2/Si interface under the influence of the electric field, suggesting the presence of negative charges in HfO2. After TiN was deposited by chemical vapor deposition, no large change in the defect species was observed. After TiN was deposited by physical vapor deposition, however, positive charges were introduced at the TiN/HfO2 interface, which were associated with the incorporation of nitride into HfO2 and/or the plasma damage at the surface of HfO2, and the resultant formation of positively charged oxygen vacancies. [ABSTRACT FROM AUTHOR]

The impact of nitridation on open volumes in thin HfSiOx films fabricated on Si substrates by atomic layer deposition was studied using monoenergetic positron beams. For HfSiOx, positrons were found to annihilate from the trapped state due to open volumes which exist intrinsically in an amorphous structure. After plasma nitridation, the size of open volumes decreased at a nitrogen concentration of about 20 at. %. An expansion of open volumes, however, was observed after postnitridation annealing (PNA) (1050 °C, 5 s). We found that the size of open volumes increased with increasing nitrogen concentration in HfSiOx. The change in the size of open volumes was attributed to the trapping of nitrogen by open volumes, and an incorporation of nitrogen into the amorphous matrix of HfSiOx during PNA. We also examined the role of nitrogen in HfSiOx using x-ray photoelectron spectroscopy and first principles calculations. [ABSTRACT FROM AUTHOR]

Thin Hf0.6Si0.4Ox and Hf0.3Al0.7Ox films fabricated by metal-organic chemical-vapor deposition and atomic-layer-deposition techniques were characterized using monoenergetic positron beams. Measurements of the Doppler broadening spectra of annihilation radiation and the lifetime spectra of positions indicated that positrons annihilated from the trapped state by open volumes that exist intrinsically in amorphous structures of the films. For HfSiOx, the mean size of the open volumes and their size distribution decreased with increasing postdeposition annealing (PDA) temperature. For HfAlOx, although the overall behavior of the open volumes in response to annealing was similar to that for HfSiOx, PDA caused a separation of the mean size of the open volumes. When this separation occurred, the value of the line-shape parameter S increased, suggesting an oxygen deficiency in the amorphous matrix. This fragmentation of the amorphous matrix can be suppressed by decreasing the annealing time. [ABSTRACT FROM AUTHOR]

The annealing behaviors of oxygen vacancies introduced by the epitaxial growth of thin SrTiO3 and Al2O3 films on SrTiO3 substrates were studied by using a monoenergetic positron beam. The films were grown by molecular-beam epitaxy without using an oxidant. The Doppler broadening spectra of the annihilation radiation were measured as a function of the incident positron energy for samples fabricated under various growth conditions. The line-shape parameter S, corresponding to the annihilation of positrons in the substrate, was increased by the film growth, suggesting diffusion of oxygen from the substrate into the film and a resultant introduction of vacancies (mainly oxygen vacancies). A clear correlation between the value of S and the substrate conductivity was obtained. From isochronal annealing experiments, the Al2O3 thin film was found to suppress the penetration of oxygen from the atmosphere for annealing temperatures below 600 °C. Degradation of the film’s oxygen blocking property occurred due to the annealing at 700 °C, and this was attributed to the oxidation of the Al2O3 by the atmosphere and the resultant introduction of vacancy-type defects. [ABSTRACT FROM AUTHOR]

Vacancy-type defects in the CeO[sub 2]/SrTiO[sub 3] structure were studied by means of positron annihilation. Thin CeO[sub 2] films were grown on SrTiO[sub 3] substrates by molecular-beam epitaxy without using an oxidant; oxygen was supplied by diffusion from the substrate (this process is referred to as automatic feeding epitaxy). A preferential epitaxial growth of CeO[sub 2](001) on SrTiO[sub 3](001) was observed, but an increase in the film thickness or annealing in an O[sub 2] atmosphere caused a partial growth of CeO[sub 2](110). The introduction of this phase was found to correlate with the reduction in the concentration of vacancy-type defects. The species of defects introduced into the SrTiO[sub 3] substrate was found to be not only oxygen vacancies but also Sr vacancies or their complexes. We discuss the mechanism that introduced cation vacancies in terms of oxygen nonstoichiometry. We found the trapping rate of positrons by Sr vacancies to depend on the sample temperature. This was associated with the temperature dependence of the dielectric constant near the defects or the presence of shallow trapping centers. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A study on the impact of TiN deposition on thin HfO2 films formed on Si substrates is conducted using x-ray photoelectron spectroscopy and a monoenergetic positron beam. For the predeposition sample, the positrons implanted into Si are found to diffuse toward the HfO2/Si interface under the influence of the electric field, suggesting the presence of negative charges in HfO2.