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  1. Woo SP, Yasin Z, Tan SH, Kajihara H, Fujita T
    Zookeys, 2015.
    PMID: 26798290 DOI: 10.3897/zookeys.545.6415
    Five sea cucumber species including one new species of the genus Stichopus are reported from the shallow coral reefs of Straits of Malacca. The new species Stichopus fusiformiossa has unusual fusiform spicules in the tentacles, which are not found in the other species of the genus. Pseudo-tables and large perforated plates are newly recorded for Stichopus hermanni Semper, 1868 and Stichopus vastus Sluiter, 1887, respectively.
  2. Jamal A, Babazono A, Li Y, Yoshida S, Fujita T
    Medicine (Baltimore), 2020 May;99(18):e19871.
    PMID: 32358355 DOI: 10.1097/MD.0000000000019871
    The presence of comorbid conditions along with heterogeneity in terms of healthcare practices and service delivery could have a significant impact on the patient's outcomes. With a strong interest in social epidemiology to examine the impact of health services and variations on health outcomes, the current study was conducted to analyse the incidence of hemodialysis-associated infection (HAI) as well as its associated factors, and to quantify the extent to which the contextual effects of the care facility and regional variations influence the risk of HAI.A total of 6111 patients with end-stage renal disease who received hemodialysis treatment between 1 October 2015 and 31 March 2016 were identified from the insurance claim database as a population-based, close-cohort retrospective study. Patients were followed for one year from April 1, 2016 to March 31, 2017. A total of 200 HAI cases were observed during the follow-up and 12 patients died within 90 days of the onset of HAI. Increased risks for HAI were associated with moderate (HR 1.73, 95% confidence interval [CI] 1.00-2.98) and severe (HR 1.87, 95% CI 1.11-3.14) comorbid conditions as well as malignancy (HR 1.36, 95% CI 1.00-1.85). Increased risk was also seen among patients who received hemodialysis treatment from clinics (HR 2.49, 95% CI 1.1-5.33). However, these statistics were no longer significant when variations at the level of care facilities were statistically controlled. In univariate analyses, no statistically significant association was observed between 90-day mortality and baseline patients, and the characteristics of the care facility.The results of the multivariate, multilevel analyses indicated that HAI variations were only significant at the care facility level (σ 2.07, 95% CI 1.3-3.2) and were largely explained by the heterogeneity between care facilities. The results of this study highlight the need to look beyond the influence of patient-level characteristics when developing policies that aim at improving the quality of hemodialysis healthcare and service delivery in Japan.
  3. Ise Y, Woo SP, Tan SH, Fujita T
    Zootaxa, 2019 Aug 20;4657(3):zootaxa.4657.3.3.
    PMID: 31716770 DOI: 10.11646/zootaxa.4657.3.3
    Two new species of thinly encrusting sponge Hamacantha (Demospongiae, Merliida, Hamacanthidae) are described from Japan. Hamacantha (Vomerula) mamoi sp. nov. was collected from Sagami Bay, and Hamacantha (Vomerula) umisachii sp. nov. from off Hachijo Island. This is the first record of Hamacantha and the Hamacanthidae from Japan. H. (V.) mamoi sp. nov. is characterized by having styles, two types of diancistras and one of sigmas. Only two known species have the same spicule composition: H. (V.) acerata Lévi, 1993 and H. (V.) esperioides Ridley Dendy, 1886, described from New Caledonia, and south-west Africa and south-east South America, respectively. H. (V.) acerata has larger diancistras and much smaller sigmas compared with those of H. (V.) mamoi sp. nov. H. (V.) esperioides can be separated by having larger styles and smaller sigmas than those of H. (V.) mamoi sp. nov. H. (V.) umisachii sp. nov is characterized by having styles, diancistras, cyrtancistra-like diancistras and sigmas. Hamacantha (V.) carteri Topsent, 1904 seems to have similar spicule composition, however the size of all spicule types is different.
  4. Fujita T, Babazono A, Kim SA, Jamal A, Li Y
    BMC Geriatr, 2021 12 15;21(1):707.
    PMID: 34911495 DOI: 10.1186/s12877-021-02685-x
    BACKGROUND: The number of patients with Parkinson's disease among older adults is rapidly increasing. Such patients mostly take medication and require regular physician visits. However, the effect of physician visit frequency for the treatment for Parkinson's disease has not been evaluated. This study aimed to evaluate the impact of physician visit frequency for Parkinson's disease treatment on mortality, healthcare days, and healthcare and long-term care costs among older adults.

    METHODS: This study employed a retrospective cohort design utilizing claims data from the Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare Insurance and Long-Term Care Insurance. Patients aged ≥75 years who were newly diagnosed with Parkinson's disease in 2014 were included in this study, following the onset of Parkinson's disease to March 31, 2019. We calculated the restricted mean survival time to evaluate mortality, focusing on the frequency of physician visits for Parkinson's disease treatment. Inpatient days, outpatient days, and healthcare and long-term care costs per month were calculated using a generalized linear model.

    RESULTS: There were 2224 participants, with 46.5% mortality among those with a higher frequency of physician visits and 56.4% among those with a lower frequency of physician visits. A higher frequency of physician visits was associated with a significant increase in survival time (1.57 months at 24 months and 5.00 months at 60 months) after the onset of Parkinson's disease and a decrease in inpatient days and healthcare costs compared to a lower frequency of physician visits.

    CONCLUSIONS: A higher frequency of physician visits was significantly associated with longer survival time, fewer inpatient days, and lower healthcare costs. Caregivers should support patients with Parkinson's disease to visit physicians regularly for their treatment.

  5. Fujita T, Babazono A, Jiang P, Jamal A, Li Y
    Pharmacoepidemiol Drug Saf, 2022 02;31(2):187-195.
    PMID: 34529297 DOI: 10.1002/pds.5359
    PURPOSE: Smoking is an important public health issue. Although measures to support smoking cessation have been implemented worldwide, smokers often fail to quit smoking after receiving pharmacotherapies for nicotine dependence. The present study evaluated the cost-effectiveness of varenicline for smoking cessation compared with no pharmacotherapy using actual paid medical cost data in Japan.

    METHODS: This was a retrospective cohort study of 3657 subjects who had quit smoking with varenicline or no pharmacotherapy. We extracted health examination and medical claim data from a health insurer database for the period 2012-2015. We calculated the incremental cost-effective ratio (ICER) of varenicline using actual paid medical costs for nicotine dependence and the number needed to treat to maintain smoking cessation compared with no pharmacotherapy, considering sex, age, income, and occupation.

    RESULTS: The 1- and 2-year smoking cessation maintenance rates were 69.7% and 62.4%, respectively. We found that 8.8% of subjects who quit smoking used varenicline for nicotine dependence and the cost per person was Japanese Yen (JPY) 52 177 (U.S. dollars [USD] 474; USD 1 = JPY 110). The ICER of varenicline was dominant when comparing 2-year cessation with 1-year cessation. Male, age <40 years, low income, and manufacturing workers were the most cost-effective variables.

    CONCLUSIONS: The cost-effective variables of varenicline in the real world were investigated. The results of this study strengthen the evidence regarding which type of people should be targeted for measures to support smoking cessation using varenicline.

  6. Li Y, Babazono A, Jamal A, Fujita T, Yoshida S, Kim SA
    Int J Equity Health, 2021 03 16;20(1):80.
    PMID: 33726747 DOI: 10.1186/s12939-021-01415-4
    BACKGROUND: Variation in health care delivery among regions and hospitals has been observed worldwide and reported to have resulted in health inequalities. Regional variation of percutaneous coronary intervention (PCI) was previously reported in Japan. This study aimed to assess the small-area and hospital-level variations and to examine the influence of patient and hospital characteristics on the use of PCI.

    METHODS: Data provided by the Fukuoka Prefecture Latter-stage Elderly Insurance Association was used. There were 11,821 patients aged ≥65 years with acute coronary syndromes who were identified from 2015 to 2017. Three-level multilevel logistic regression analyses were performed to quantify the small-area and hospital variations, as well as, to identify the determinants of PCI use.

    RESULTS: The results showed significant variation (δ2 = 0.744) and increased PCI use (MOR = 2.425) at the hospital level. After controlling patient- and hospital-level characteristics, a large proportional change in cluster variance was found at the hospital level (PCV 14.7%). Fixed-effect estimation results showed that females, patients aged ≥80 years old, hypertension and dyslipidemia had significant association with the use of PCI. Hospitals with high physician density had a significantly positive relationship with PCI use.

    CONCLUSIONS: Patients receiving care in hospitals located in small areas have equitable access to PCI. Hospital-level variation might be originated from the oversupply of physicians. A balanced number of physicians and beds should be taken into consideration during healthcare allocation. A treatment process guideline on PCI targeting older patients is also needed to ensure a more equitable access for healthcare resources.

  7. Jamal A, Babazono A, Li Y, Fujita T, Yoshida S, Kim SA
    PLoS One, 2021;16(5):e0252196.
    PMID: 34033671 DOI: 10.1371/journal.pone.0252196
    Variations in health care outcomes and services potentially indicate resource allocation inefficiency. Therefore, this study was conducted to examine variations in mortality and hospitalization cases among end-stage renal disease (ESRD) patients receiving hemodialysis (HD) care from medical facilities located in 13 secondary medical care areas (SMAs) of Fukuoka prefecture, Japan. The research was designed as a retrospective, cross-sectional study using insurance claims data. The subjects of the study were older patients (over 65 years old) insured by the Fukuoka prefecture's Latter-Stage Elderly Healthcare Insurance. Using an electronic claims database, we identified patients with chronic kidney disease (CKD) who had received HD care from April 1, 2017 to March 31, 2018. The CKD status was identified using International Classification of Disease, 10th revision code, and HD maintenance status was ascertained using specific insurance procedure codes. A total of 5,243 patients met our inclusion criteria and their records were subsequently reviewed. About 73% (n = 3,809) of patients had admission records during the period studied. Thus, the data regarding hospital length of stay (LOS) and admission costs were analyzed separately. Significant differences in terms of increased risks in hospitalization were evident in a number of SMAs. An increase in mortality risk due to heart failure and malignancy was observed in two separate SMAs. Also, analyzed LOS, total hospitalization cost, and cost per day according to SMAs showed statistically significant variations. The findings highlight the magnitude of the burden of CKD and ESRD in the community. The high prevalence of ESRD, associated mortality, and hospitalized HD patients signal the need for clinicians to assume broader roles in measures against chronic kidney disease through involvement in community awareness programs. To improve patient outcomes, improvement of regional health care provision, the level of medical care, and the development of existing human resources are needed.
  8. Jamal A, Babazono A, Li Y, Yoshida S, Fujita T, Kim SA
    Am J Med Qual, 2021 5 20;36(5):345-354.
    PMID: 34010165 DOI: 10.1097/01.JMQ.0000735484.44163.ce
    The authors examined variations in hemodialysis care and quantified the effect of these variations on all-cause mortality. Insurance claims data from April 1, 2017 to March 30, 2018 were reviewed. In total, 2895 hospital patients were identified, among whom 398 died from various causes. Controlling effects of the facility and secondary medical care areas, all-cause mortality was associated with older age, heart failure, malignancy, cerebral stroke, severe comorbidity, and the first and ninth centile of physician density. Multilevel analyses indicated a significant variation at facility level (σ22 0.27, 95% confidence interval: 0.09-0.49). Inclusion of all covariates in the final model significantly reduced facility-level variance. Physician density emerged as an important factor affecting survival outcome; thus, a review of workforce and resource allocation policies is needed. Better clinical management and standardized work processes are necessary to attenuate differences in hospital practice patterns.
  9. Li Y, Babazono A, Ohmori T, Jamal A, Yoshida S, Kim SA, et al.
    Popul Health Manag, 2022 Feb;25(1):23-30.
    PMID: 34076535 DOI: 10.1089/pop.2021.0070
    This study aimed to comprehensively evaluate whether income affects long-term health outcomes for older patients who underwent percutaneous coronary intervention (PCI) provided by a universal health coverage system. Data were from the Latter Stage Elderly Healthcare Insurance database in Fukuoka Prefecture, Japan. A total of 5625 individuals aged ≥65 years who underwent PCI in 2014-2016 were included. Cox proportional hazards models were used to assess the association between income status and the incidence of health outcomes. With a median follow-up of 1095 days, 554 acute myocardial infarction (AMI) cases, 1075 stroke cases, 1690 repeat revascularization cases, and 1094 deaths were observed. Risk of all-cause mortality decreased significantly with increasing income level in both unadjusted and adjusted Cox regression models. Patients in the low-income level had a significantly higher rate of AMI (log-rank P = 0.003), stroke (log-rank P = 0.039), and all-cause mortality (log-rank P = 0.001) compared with patients in the high-income level. Observed rates for repeat revascularization also were high in the first year after PCI. In the Japanese universal health setting, low-income patients had a comparatively higher mortality risk after PCI. Poor long-term outcomes might be attributed to patients' baseline characteristics rather than treatment processes.
  10. Nakamoto H, Fujita T, Origasa H, Isono M, Kurumatani H, Okada K, et al.
    BMC Nephrol, 2014;15:153.
    PMID: 25233856 DOI: 10.1186/1471-2369-15-153
    Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial.
  11. Jamal A, Babazono A, Liu N, Yamao R, Fujita T, Kim SA, et al.
    Metab Syndr Relat Disord, 2024 Feb;22(1):27-38.
    PMID: 38350086 DOI: 10.1089/met.2023.0055
    Background: Serum gamma-glutamyltransferase (γ-GT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels often increase in metabolic diseases. Objective: This study was conducted to determine which liver enzymes are strongly associated with metabolic syndrome (MetS), how they interact to produce different probability estimates, and what cutoff levels should be used to guide clinical decision-making. Methods: The researchers examined the insurance-based medical checkup data of 293,610 employees ≥35 years years of age, who underwent medical checkups between April 1, 2016, and March 31, 2017. Liver enzyme levels were grouped into quartiles. The association and interaction of liver enzymes with MetS were examined using logistic regression, and receiver operating characteristic (ROC) analyses were used to determine the optimal cutoff values for each liver enzyme in detecting the prevalence of MetS. Results: High levels of γ-GT and ALT were more strongly associated with MetS than AST. At various levels, the tested liver enzymes were found interactive, and associated with the likelihood of MetS prevalence. ROC analysis underscored the significance of all liver enzymes in predicting the development of MetS. The cutoff values for each liver enzyme were determined. Conclusion: This findings of this study directly support the identification of MetS risks within the population, prioritize prevention strategies, and potentially inform policy formulation.
  12. Li Y, Babazono A, Jamal A, Liu N, Fujita T, Zhao R, et al.
    Soc Sci Med, 2022 Dec;314:115468.
    PMID: 36327638 DOI: 10.1016/j.socscimed.2022.115468
    Metabolic syndrome (MetS) prevalence has increased globally with considerable morbidity and economic burden at both individual and national levels. Japan is the first and only country that has introduced a nationwide lifestyle guidance intervention program to manage and control MetS. We conducted a quasi-experiment approach-regression discontinuity design-to evaluate the impact of this intervention on health outcomes at the population level. We retrospectively collected data of adults aged ≥35 years who participated in health checkups in 2015. Age in 2015 was used as the assignment variable, and an age of 40 years old was the threshold because those with MetS aged ≥40 were required to receive lifestyle guidance intervention. Among 26,772 MetS adults, those who received the intervention had significant reductions in obesity measurements (bodyweight, waist circumference, and body mass index [BMI]) after 1 year of this intervention. Blood pressure was also significantly reduced in men after 1 year of undertaking the intervention. The results were similar when including demographic, socioeconomic, and behavioral covariates and using alternative functional forms to estimate the impact, or when bandwidths around intervention thresholds were changed. Our results showed that lifestyle guidance intervention for MetS has an important impact on weight loss and blood pressure reduction at the population level. This intervention could address the high burden of obesity and cardiovascular diseases in Japan and other countries with an unmet need for MetS prevention and management.
  13. Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, et al.
    Future Oncol, 2019 Jul;15(21):2489-2501.
    PMID: 31140297 DOI: 10.2217/fon-2019-0143
    Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.
  14. Kumari R, Guo Z, Kumar A, Wiens M, Gangappa S, Katz JM, et al.
    Antiviral Res, 2020 Apr;176:104747.
    PMID: 32092305 DOI: 10.1016/j.antiviral.2020.104747
    Influenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer Binding Protein beta (C/EBPβ) binding site in the RIG-I promoter as a repressor element, and show that NS1 promotes C/EBPβ phosphorylation and its recruitment to the RIG-I promoter as a C/EBPβ/NS1 complex. C/EBPβ overexpression and siRNA knockdown in human lung epithelial cells resulted in suppression and activation of RIG-I expression respectively, implying a negative regulatory role of C/EBPβ. Further, C/EBPβ phosphorylation, its interaction with NS1 and occupancy at the RIG-I promoter was associated with RIG-I transcriptional inhibition. These findings provide an important insight into the molecular mechanism by which influenza NS1 commandeers RIG-I transcriptional regulation and suppresses host antiviral responses.
  15. Nakamoto H, Yu XQ, Kim S, Origasa H, Zheng H, Chen J, et al.
    Ther Apher Dial, 2020 Feb;24(1):42-55.
    PMID: 31119846 DOI: 10.1111/1744-9987.12840
    TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.
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