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Article ; Online: Estimation of the causal effects of time-varying treatments in nested case-control studies using marginal structural Cox models.

Takeuchi, Yoshinori / Hagiwawa, Yasuhiro / Komukai, Sho / Matsuyama, Yutaka

2024 Volume 80, Issue 1

Abstract: When estimating the causal effects of time-varying treatments on survival in nested case-control (NCC) studies, marginal structural Cox models (Cox-MSMs) with inverse probability weights (IPWs) are a natural approach. However, calculating IPWs from the ... ...

Abstract	When estimating the causal effects of time-varying treatments on survival in nested case-control (NCC) studies, marginal structural Cox models (Cox-MSMs) with inverse probability weights (IPWs) are a natural approach. However, calculating IPWs from the cases and controls is difficult because they are not random samples from the full cohort, and the number of subjects may be insufficient for calculation. To overcome these difficulties, we propose a method for calculating IPWs to fit Cox-MSMs to NCC sampling data. We estimate the IPWs using a pseudo-likelihood estimation method with an inverse probability of sampling weight using NCC samples, and additional samples of subjects who experience treatment changes and subjects whose follow-up is censored are required to calculate the weights. Our method only requires covariate histories for the samples. The confidence intervals are calculated from the robust variance estimator for the NCC sampling data. We also derive the asymptotic properties of the estimator of Cox-MSM under NCC sampling. The proposed methods will allow researchers to apply several case-control matching methods to improve statistical efficiency. A simulation study was conducted to evaluate the finite sample performance of the proposed method. We also applied our method to a motivating pharmacoepidemiological study examining the effect of statins on the incidence of coronary heart disease. The proposed method may be useful for estimating the causal effects of time-varying treatments in NCC studies.
MeSH term(s)	Humans ; Proportional Hazards Models ; Probability ; Computer Simulation ; Case-Control Studies ; Research Design ; Models, Statistical
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	213543-7
ISSN	1541-0420 ; 0099-4987 ; 0006-341X
ISSN (online)	1541-0420
ISSN	0099-4987 ; 0006-341X
DOI	10.1093/biomtc/ujae005
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Article: [Medical Statistics as a Foundation of Biomedical Research].

Murakami, Yoshitaka / Takeuchi, Yoshinori

Brain and nerve = Shinkei kenkyu no shinpo

2022 Volume 74, Issue 4, Page(s) 341–351

Abstract: Biomedical research commonly deals with measured values in humans, laboratory animals, and cells. These collections of measured variables, termed data, are analyzed to achieve scientific objectives. In this review, we present an overview of medical ... ...

Abstract	Biomedical research commonly deals with measured values in humans, laboratory animals, and cells. These collections of measured variables, termed data, are analyzed to achieve scientific objectives. In this review, we present an overview of medical statistics, including its concepts, methods, and tips, for biomedical research applications. We first introduce various concepts of medical statistics, such as true values (that would never be seen in the real world), measured values (actual measurements), bias, and random error. Medical statistics deals with the removal of bias and control of random errors to generate scientific evidence. As a statistical method, data description (or data visualization) is the first step that analysts use to examine data. Data descriptions reveal the patterns, trends, and relationships of the variables. Subsequently, data are analyzed using interval estimation (95% confidence intervals) and statistical hypothesis testing to guide conclusions. Herein, we address the limitations of hypothesis testing and the advantages of using 95% confidence intervals. Moreover, we provide a summary of multiple comparison procedures that allow the simultaneous testing of two or more null hypotheses.
MeSH term(s)	Animals ; Biomedical Research ; Humans ; Public Health ; Research Design
Language	Japanese
Publishing date	2022-04-18
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390389-8
ISSN	1344-8129 ; 1881-6096 ; 0006-8969
ISSN (online)	1344-8129
ISSN	1881-6096 ; 0006-8969
DOI	10.11477/mf.1416202041
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Zs.A 398: Show issues

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Article ; Online: The utility of the self-controlled study design for pharmacoepidemiological studies without an active comparator medication using a medical information database: An application to assess the risk of varenicline on cardiovascular outcomes.

Yokoyama, Ryo / Takeuchi, Yoshinori / Kumamaru, Hiraku / Matsuyama, Yutaka

Pharmacoepidemiology and drug safety

2023 Volume 32, Issue 10, Page(s) 1068–1076

Abstract: Purpose: To illustrate the utility of the self-controlled study design for studies without an active comparator, we compared the results of a cohort design study with a non-user comparator with those of a self-controlled design study in evaluating the ... ...

Abstract	Purpose: To illustrate the utility of the self-controlled study design for studies without an active comparator, we compared the results of a cohort design study with a non-user comparator with those of a self-controlled design study in evaluating the risk of varenicline on cardiovascular outcomes, using a Japanese medical claims database. Methods: The participating smokers were identified from health-screening results collected between May 2008 and April 2017. Using a non-user-comparator cohort study design, we estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of varenicline on initial hospitalization with cardiovascular outcomes using Cox's model adjusted for patients' sex, age, medical history, medication history, and health-screening results. Using a self-controlled study design, the within-subject HR was estimated using a stratified Cox's model adjusted for medical history, medication history, and health-screening results. The estimate from a recent meta-analysis was considered the gold standard (risk ratio: 1.03). Results: We identified 460 464 smokers (398 694 males [86.6%]; mean (standard deviation) age: 42.9 [10.8] years) in the database. Of these, 11 561 had been dispensed varenicline at least once, and 4511 had experienced cardiovascular outcomes. The estimate of the non-user-comparator cohort study design exceeded the gold standard (HR [95% CI]: 2.04 [1.22-3.42]), whereas that of the self-controlled study design was close to the gold standard (within-subject HR [95% CI]: 1.12 [0.27-4.70]). Conclusions: The self-controlled study design is useful alternative to a non-user-comparator cohort design when evaluating the risk of medications relative to their non-use, based on a medical information database.
MeSH term(s)	Male ; Humans ; Adult ; Varenicline/adverse effects ; Bupropion ; Smoking Cessation/methods ; Cohort Studies ; Proportional Hazards Models
Chemical Substances	Varenicline (W6HS99O8ZO) ; Bupropion (01ZG3TPX31)
Language	English
Publishing date	2023-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099748-9
ISSN	1099-1557 ; 1053-8569
ISSN (online)	1099-1557
ISSN	1053-8569
DOI	10.1002/pds.5634
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Article ; Online: Genome-wide screening of upstream transcription factors using an expression library.

Yahagi, Naoya / Takeuchi, Yoshinori

F1000Research

2021 Volume 10, Page(s) 51

Abstract: The identification of upstream transcription factors regulating the expression of a gene is generally not an easy process. To facilitate this task, we constructed an expression cDNA library named Transcription Factor Expression Library (TFEL), which is ... ...

Abstract	The identification of upstream transcription factors regulating the expression of a gene is generally not an easy process. To facilitate this task, we constructed an expression cDNA library named Transcription Factor Expression Library (TFEL), which is composed of nearly all the transcription factors in the mouse genome. Genome-wide screening using this library (TFEL scan method) enables us to easily identify transcription factors controlling any given promoter or enhancer of interest in a chromosomal context-dependent manner. Thus, TFEL scan method is a powerful approach to explore transcriptional regulatory networks.
Language	English
Publishing date	2021-01-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.27532.2
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Article ; Online: Genome-wide screening of upstream transcription factors using an expression library [version 2; peer review

Naoya Yahagi / Yoshinori Takeuchi

F1000Research, Vol

2 approved]

2021 Volume 10

Abstract	The identification of upstream transcription factors regulating the expression of a gene is generally not an easy process. To facilitate this task, we constructed an expression cDNA library named Transcription Factor Expression Library (TFEL), which is composed of nearly all the transcription factors in the mouse genome. Genome-wide screening using this library (TFEL scan method) enables us to easily identify transcription factors controlling any given promoter or enhancer of interest in a chromosomal context-dependent manner. Thus, TFEL scan method is a powerful approach to explore transcriptional regulatory networks.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Real-world burden and treatment of chronic rhinosinusitis in Japan: A retrospective claims database analysis.

Yoshikawa, Mamoru / Sunaga, Yoshinori / Koshiba, Ryuji / Inukai, Miho / Takeuchi, Makiko

Laryngoscope investigative otolaryngology

2023 Volume 8, Issue 2, Page(s) 346–356

Abstract: Objectives: Chronic rhinosinusitis (CRS) is a heterogeneous disease, which can be subdivided into CRS with (CRSwNP) or without (CRSsNP) nasal polyps. An intractable form of CRSwNP that is associated with an eosinophil-dominant inflammatory cell ... ...

Abstract	Objectives: Chronic rhinosinusitis (CRS) is a heterogeneous disease, which can be subdivided into CRS with (CRSwNP) or without (CRSsNP) nasal polyps. An intractable form of CRSwNP that is associated with an eosinophil-dominant inflammatory cell infiltration (eosinophilic CRS) has become more prevalent in Japan. There is currently limited information on the burden of CRS in Japan and treatment approaches used in real-world practice. Methods: This retrospective, observational, comparative cohort study used information from the Japanese JMDC insurance claims database (study period April 1, 2015, to March 31, 2020). A CRS cohort was identified and matched with a control group without CRS. The primary objective was to clarify disease burden and treatment approaches by comparing comorbidities, healthcare resource utilization (HRU), and drug prescriptions in the CRS and non-CRS groups. Results: In total, 23,256 individuals with CRS (1762 with CRSwNP and 21,494 with CRSsNP) were matched with 23,256 controls. The mean age was 45 years and the majority of individuals were male (57%). Individuals with CRS had a higher disease burden than controls, with more frequent comorbidities (particularly, type 2 inflammatory disease [e.g., allergic rhinitis and asthma], and those caused by systemic corticosteroids [SCS]), and higher HRU (including outpatient visits, laboratory examinations and surgical procedures). Further, individuals with CRS were prescribed more medications, both for CRS (including SCS) and non-CRS conditions, than controls. Conclusion: In Japan, CRS is associated with a high disease burden, and multiple treatment approaches are used in affected individuals, including long-term SCS, which is generally not recommended. Level of evidence: 3.
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article
ISSN	2378-8038
ISSN	2378-8038
DOI	10.1002/lio2.1027
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Article ; Online: Future health insurance system in an aged society with a low birth rate.

Sasai, Yoshinori / Suzuki, Yusuke / Takeuchi, Yoshimasa

Journal of prosthodontic research

2020 Volume 64, Issue 4, Page(s) 515–516

MeSH term(s)	Birth Rate ; Insurance, Health
Language	English
Publishing date	2020-02-13
Publishing country	Japan
Document type	Letter
ZDB-ID	2470657-7
ISSN	2212-4632 ; 1883-1958
ISSN (online)	2212-4632
ISSN	1883-1958
DOI	10.1016/j.jpor.2019.10.004
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Article: Association Between Ego-Resilience and Social Isolation Among Urban Older People.

Hashimoto, Kazuaki / Takeuchi, Takeaki / Ihara, Kazushige / Obuchi, Shuichi / Kawai, Hisashi / Hirano, Hirohiko / Fujiwara, Yoshinori / Hunkyung, Kim / Watanabe, Yutaka / Hashizume, Masahiro

Gerontology & geriatric medicine

2024 Volume 10, Page(s) 23337214241238069

Abstract: Social isolation among older adults affects their physical and mental health. Ego-resilience is associated with flexible adaptation to various environments and acceptable behaviors. However, its association with social isolation among older people is ... ...

Abstract	Social isolation among older adults affects their physical and mental health. Ego-resilience is associated with flexible adaptation to various environments and acceptable behaviors. However, its association with social isolation among older people is unclear. Therefore, a health survey was conducted with 510 adults aged 65 years or older to assess social isolation, its associated factors, and ego resilience. The results showed that the social isolation group had a lower median ego-resiliency scale score (42.0) compared to the non-social isolation group (38.0). The social isolation group were mostly males without spouses, took time to move, had more depressive moods, and poorer subjective health status. The non-social isolated group had faster maximum walking speed. Low ego-resilience was newly identified as a factor associated with social isolation among older people, as were being male, having no spouse, and depressive symptoms. Mediation analysis revealed that ego-resilience affected social isolation and was partially mediated by depressive symptoms.
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844974-5
ISSN	2333-7214 ; 2333-7214
ISSN (online)	2333-7214
ISSN	2333-7214
DOI	10.1177/23337214241238069
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Article ; Online: Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds.

Takeuchi, Reon / Fujimoto, Junko / Taguchi, Yoshinori / Ide, Ryuji / Kyan, Ryuji / Sato, Kohei / Mase, Nobuyuki / Yokoyama, Masaru / Harada, Shigeyoshi / Narumi, Tetsuo

Chemical & pharmaceutical bulletin

2024 Volume 72, Issue 3, Page(s) 330–335

Abstract: A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we ... ...

Abstract	A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.
MeSH term(s)	Oleanolic Acid/chemistry ; HIV-1
Chemical Substances	Oleanolic Acid (6SMK8R7TGJ)
Language	English
Publishing date	2024-02-16
Publishing country	Japan
Document type	Journal Article
ZDB-ID	213307-6
ISSN	1347-5223 ; 0009-2363
ISSN (online)	1347-5223
ISSN	0009-2363
DOI	10.1248/cpb.c23-00891
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Article: SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA.

Morita, Naoko / Tanaka, Yukie / Takeuchi, Kenji / Kitagawa, Yoshinori / Sakuma, Ryusuke / Koide, Naoki / Komatsu, Takayuki

Frontiers in microbiology

2022 Volume 13, Page(s) 780534

Abstract: Macrophages play a central role in the innate immune response to respiratory viral infections through pro-inflammatory factor secretion and phagocytosis. However, as a countermeasure, viral pathogens have evolved virulence factors to antagonize ... ...

Abstract	Macrophages play a central role in the innate immune response to respiratory viral infections through pro-inflammatory factor secretion and phagocytosis. However, as a countermeasure, viral pathogens have evolved virulence factors to antagonize macrophage function. In our recent
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.780534
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