Effect of the Japanese medical office system on job satisfaction, loyalty, engagement, and organizational commitment of medical practitioners: a survey of cardiologists in the acute care setting.

BACKGROUND: In Japan, medical doctors have traditionally been assigned from university medical offices, under the medical office system. The present study examined the effects of the medical office system on job satisfaction, engagement, loyalty, and organizational commitment among cardiologists. METHODS: In this study, a survey of 156 cardiologists was conducted, from April 22, 2023, to May 21, 2023, to examine the effect of the medical office system on employee job satisfaction, employee engagement, and organizational commitment. RESULTS: Compared with the group that belonged to a medical office system (affiliated group, n = 117), the group that did not belong to a medical office system (non-affiliated group, n = 39) was affiliated to hospitals with a smaller number of beds. The results of the factor analysis showed that four types of hospital management styles were generated, namely, environment-, loyalty-building-, treatment-, and philosophy-oriented hospitals. There is an indication that the philosophy-oriented management style was adopted at the workplaces of the non-affiliated group. The treatment-oriented style also tended to be higher in the non-affiliated group than in the affiliated group. Furthermore, the non-affiliated group had higher organizational commitment, indicating that they were more likely to agree with the management philosophy set forth by hospital executives. CONCLUSION: Although the medical office system did not affect job satisfaction, compared with medical doctors with the affiliated group, those with the non-affiliated group tended to work in hospitals that emphasized philosophy-oriented management, and they received moderate compensation while practicing in an environment suitable for their specialty. These results suggest that the medical office system makes it difficult for medical doctors to have high workplace loyalty, engagement, and commitment to the hospital to which they are dispatched.

Transformation of the Cardiovascular Clinics in Japan　- How to Overcome Crisis Due to Changes in the External Environment.

The first percutaneous coronary intervention (PCI) was performed in September 1977, and after 1980 this minimally invasive treatment was established in Japan. To deliver this treatment to a larger population, a number of cardiovascular clinics emerged across the country in the 2000s, and the number of PCI cases performed has been steadily increasing, to >250,000 cases per year. In the early 2000s, a single catheterization unit was profitable, if it performed a certain number of treatments and was adequately staffed without excessive capital investment. In the late 1990s, the price of a balloon catheter medical device used for PCI was approximately JPY300,000, although the price was reduced to JPY32,000, almost one-tenth in price, in the April 2022 revision of the National Health Insurance. The reimbursement of the mainstream drug-eluting stent has also decreased from JPY421,000, when it was first introduced, to JPY136,000 currently. In addition, the consumption tax and reforms in working hours will have a major impact on clinic management. We present a history of cardiovascular clinics in Japan and their present and future positions under the variable external environment.

Bilateral Subclavian Vein Occlusion in a SAPHO Syndrome Patient Who Needed an Implantable Cardioverter Defibrillator.

A 79-year-old Asian man was hospitalized because of progressive exertional dyspnea with decreasing left ventricular ejection fraction and frequent non-sustained ventricular tachycardia. Pre-procedure venography for implantable cardioverter defibrillator (ICD) implantation showed occlusion of the bilateral subclavian veins. In consideration of subcutaneous humps in the sterno-clavicular area and palmoplantar pustulosis, we diagnosed him as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and speculated that it induced peri-osteal chronic inflammation in the sterno-clavicular area, resulting in occlusion of the adjacent bilateral subclavian veins. An automatic external defibrillator (AED) was installed in the patient's house and total subcutaneous ICD was considered. Venous thrombosis in SAPHO syndrome is not frequent but has been reported. To the best of our knowledge, this is the first case of bilateral subclavian vein occlusion in a SAPHO syndrome patient who needs ICD implantation.

Biased Agonism of the Angiotensin II Type I Receptor.

Angiotensin II (AngII) type I receptor (AT1R) recognizes AngII, a cardiovascular peptide hormone that acts as a terminal effector of the renin-angiotensin system (RAS). AT1R belongs to the rhodopsin-like peptidergic family of G protein-coupled receptors (GPCRs) and serves as a therapeutic target for the treatment of cardiovascular diseases, such as hypertension, cardiac hypertrophy and heart failure. Classically, AT1R was considered to signal only through G proteins. However, recent studies have revealed that AT1R is capable of activating G protein-independent signaling that is mediated by ß-arrestins. ß-arrestin is a cytosolic scaffold that is recruited to the activated GPCRs. In vitro and ex vivo studies have demonstrated that the activation of the AT1R-ß-arrestin pathway stimulates contractility and exerts prosurvival effects in cardiomyocytes. TRV027, a potent synthetic ß-arrestin-biased ligand for AT1R, specifically activates AT1R-ß-arrestin signaling without stimulating G proteins. In preclinical studies, TRV027 not only produced vasodilation by antagonizing the AT1R-Gαq pathway but also enhanced cardiac performance by activating AT1R-ß-arrestin signaling. Because of this unique pharmacological profile, TRV027 is now being evaluated in a phase II clinical trial as a novel therapeutic for acute heart failure (AHF).

Acute Myocardial Infarction That Resulted From Poor Adherence to Medical Treatment for Giant Coronary Aneurysm.

Coronary arterial complications associated with Kawasaki disease (KD), such as a giant coronary aneurysm, determine the relative risk of future cardiac events and require lifelong medical treatment. Here, we describe a 24-year-old man who developed myocardial infarction due to poor adherence to medical treatment for a giant coronary aneurysm in the chronic phase of KD. He was hospitalized two hours after the onset of chest pain. The presence of the giant coronary aneurysm made primary percutaneous coronary intervention (PCI) difficult. However, we were able to perform primary PCI successfully utilizing previous coronary computed tomography (CT) angiographic pictures as a reference. This case provides valuable insight for the management of coronary arterial complications associated with KD. Patients in the chronic phase of KD are usually asymptomatic, even in the presence of giant coronary aneurysms which have been reported to have a high risk of morbidity and mortality. Therefore, patient education is critical for preventing poor adherence to medical treatment for coronary arterial complications. In preparation for potential coronary intervention in the future, it is also useful to perform coronary CT angiography, coronary magnetic resonance (MR) angiography, and/or coronary angiography on a regular basis while patients remain free from serious cardiac events.

Selection criteria for anticoagulants: survey of Japanese cardiologists based on their daily clinical practice: the Selection DOAC study.

BACKGROUND: In patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been utilized as an alternative to warfarin, which is known to have several limitations. This study aimed to clarify the selection criteria for anticoagulants, considering both individual patient factors and the differences between various drugs. METHODS: This study conducted a web-based questionnaire from September 20, 2023 to October 3, 2023, among physicians who were members of a cardiology-specific website. RESULTS: In total, 172 respondents were enrolled in this study. Edoxaban was the most frequently selected anticoagulant (39.1%), followed by apixaban (32.7%) and rivaroxaban (16.8%). Logistic regression analysis revealed that increased concern for adherence enhanced the frequency of selecting edoxaban (odds ratio [OR] = 2.42; p = 0.047), with the opposite trend observed for dabigatran (OR = 0.404; p = 0.029). The selection of apixaban is related to whether the patient is able to maintain a regular lifestyle, including adherence to medication schedules (OR = 1.874; p = 0.031). Furthermore, detailing activities from a medical representative, especially regarding a new indication, were found to influence drug selection for rivaroxaban (OR = 2.422; p = 0.047). CONCLUSION: This study revealed that edoxaban is the most frequently selected anticoagulant. Although prescribing cardiologists select drugs based on background factors, adherence to medication and information from medical representatives were also crucial factors in the selection process.

Selection Criteria in the Era of Perfect Competition for Drug-Eluting Stents in Association With Operator Volumes: An Operator-Volume Analysis of the Selection DES Study.

Background: This study aimed to explore the factors influencing the drug-eluting stent (DES) selection criteria of cardiologists in association with percutaneous coronary intervention (PCI) volumes and to determine whether they value further DES improvements and modifications. Methods: The survey was conducted on a group of cardiologist operators from April 10 to 30, 2023. Results: The analysis included 126 operators who answered the questions. Of these, low-, intermediate-, and high-volume operators accounted for 49 (38.9%), 47 (37.3%), and 30 (23.8%), respectively. Overall, Xience™ everolimus-eluting stent (CoCr-EES) was most frequently used, with > 70% of cardiologists using it in > 20% of their PCI practice. The percentage of selection by low-, intermediate-, and high-volume operators among the DESs used demonstrated no difference, except for dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo® stent (DTS). Logistic regression analysis revealed that low-volume operators are less likely to be affected in terms of company/sales representative (odds ratio (OR): 0.402, P = 0.031) and bending lesions (OR: 0.339, P = 0.037) for selecting DES. Low-volume operators less frequently selected Resolute Onyx™ zotarolimus-eluting stents (OR: 0.689, P = 0.043) and DTS (Drug-Eluting Stents) (OR: 0.361, P = 0.006) for PCI. Conclusions: The current study results indicate that patient background, DES performance, and product specifications were not criteria for DES selection in cardiologists with different PCI volumes in routine PCI.

Digital marketing innovation: New business models for pharmaceutical and medical device product marketing.

Background: Within the rapidly evolving healthcare landscape in Japan, digital marketing innovations are transforming pharmaceutical and medical device marketing. This study explores the emergence of new business models in the digital marketing, highlighting a transition from traditional methods to more dynamic, data-driven strategies. Methods: InsighTCROSS® is a business model that qualitatively and quantitatively examines three steps based on stratified persona images: (1) verifying the effectiveness of product marketing promotions, (2) identifying competitors from the users' perspective, and (3) developing marketing strategies to counter competition. To demonstrate the effectiveness of this model, a case study was conducted focusing on the current anticoagulant drugs, including apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin. Results: Rivaroxaban, the only drug prescribed for the prevention of thrombus and embolism formation in patients with peripheral artery disease after lower limb revascularization, garnered the most interest from interventional cardiologists performing peripheral vascular interventions, as determined by InsighTCROSS® factor analysis, confirming that the manufacturer's marketing activities have effectively penetrated the market. A survey conducted between 20 September 2023 and 3 October 2023, among members of a cardiology website, identified edoxaban as the market leader with a 39.1% share, followed by apixaban (32.7%) and rivaroxaban (16.8%). The main competitor of edoxaban was warfarin, whereas that of rivaroxaban was apixaban. Decision tree analysis was conducted using InsighTCROSS®, highlighting the strengths and weaknesses of each anticoagulant, providing strategic approaches to exploit competitive weaknesses. For edoxaban, increased use was driven by elderly and poorly adherent patients; for apixaban, high-volume percutaneous coronary intervention centers; and for rivaroxaban, the influence of medical representative detailing. It is recommended to avoid markets where these drugs have a strong presence and to focus marketing activities on leveraging their specific strengths. Conclusion: The findings suggest that digital marketing enhances product visibility and patient engagement, providing valuable insights into market behavior and consumer preferences.

Selection criteria in the era of perfect competition for drug-eluting stents - a survey of interventional cardiologists in Japan: the selection-DES study.

BACKGROUND: More than 20 years have passed since the first company introduced drug-eluting stent (DES) in 2002, but competing companies still have improved their DESs under regulatory approval. This study aimed to investigate the criteria for interventional cardiologists performing percutaneous coronary intervention (PCI) in selecting a DES. RESEARCH DESIGN AND METHODS: From 10 April 2023, to 30 April 2023, 3,422 cardiologists were requested to complete a questionnaire, of whom 126 responded to the survey. RESULTS: Overall, 86.5% of the respondents used Xience cobalt-chromium everolimus-eluting stent (Xience) in > 10% of PCI procedures. For Xience, brand loyalty and calcified lesions were important independent variables for the DES selection criteria. Ultimaster sirolimus-eluting stent (Ultimaster) was not affected by the clinical data delivered by the company, whereas the respondents were shown to seek support for their activities from the Ultimaster supplier. The relationship with the company and/or sales representative and the planned surgical procedure affected the use of Coroflex ISAR NEO sirolimus-eluting polymer-free stent. CONCLUSIONS: Patient background and lesion characteristics had little impact on the DES selection criteria, suggesting that DES performance has already reached its physical limitations to the extent that respondents may not value further improvements in performance or characteristics of DES.

CXCR7 ameliorates myocardial infarction as a ß-arrestin-biased receptor.

Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through ß-arrestin as a biased receptor. As several ß-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a ß-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited ß-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a ß-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.

Understanding Vascular Diseases: Lessons From Premature Aging Syndromes.

Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called "progerin," at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population.

A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling.

Oxidative stress has been implicated in cardiac remodeling (cardiac fibrosis and hypertrophy), which impairs cardiac function and metabolism; therefore, it is anticipated antioxidative compounds will have protective properties against cardiac remodeling. Luteolin (3',4',5,7-tetrahydroxyflavone), a widely distributed flavonoid found in many herbal extracts including celery, green pepper, perilla leaves and seeds, and chamomile, is a known to be a potent antioxidant and was previously demonstrated to exert an antifibrotic effect in the lungs and the liver. In this study, we clearly demonstrate that oral pretreatment with the higher-luteolin diet (0.035% (wt/wt)) protected against cardiac fibrosis and hypertrophy as well as a hyperoxidative state in Ang II-infused rats. In cardiac tissue, increased gene expression levels of TGFß1, CTGF, Nox2, Nox4, ANP, and BNP induced by Ang II were restored by oral pretreatment of this high-luteolin diet. In cultured rat cardiac fibroblasts, H2O2-induced TGFß1 expression and the phosphorylation of JNK were suppressed by luteolin pretreatment. In conclusion, food-derived luteolin has protective actions against Ang II-induced cardiac remodeling, which could be mediated through attenuation of oxidative stress.

Monitoring ß-arrestin recruitment via ß-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors.

Identification of cognate ligands for G protein-coupled receptors (GPCRs) provides a starting point for understanding novel regulatory mechanisms. Although GPCR ligands have typically been evaluated through the activation of heterotrimeric G proteins, recent studies have shown that GPCRs signal not only through G proteins but also through ß-arrestins. As such, monitoring ß-arrestin signaling instead of G protein signaling will increase the likelihood of identifying currently unknown ligands, including ß-arrestin-biased agonists. Here, we developed a cell-based assay for monitoring ligand-dependent GPCR-ß-arrestin interaction via ß-lactamase enzyme fragment complementation. Inter alia, ß-lactamase is a superior reporter enzyme because of its cell-permeable fluorescent substrate. This substrate makes the assay non-destructive and compatible with fluorescence-activated cell sorting (FACS). In a reporter cell, complementary fragments of ß-lactamase (α and ω) were fused to ß-arrestin 2 and GPCR, respectively. Ligand stimulation initiated the interaction of these chimeric proteins (ß-arrestin-α and GPCR-ω), and this inducible interaction was measured through reconstituted ß-lactamase activity. Utilizing this system, we screened various mammalian tissue extracts for agonistic activities on human bombesin receptor subtype 3 (hBRS3). We purified peptide E as a low-affinity ligand for hBRS3, which was also found to be an agonist for the other two mammalian bombesin receptors such as gastrin-releasing peptide receptor (GRPR) and neuromedin B receptor (NMBR). Successful purification of peptide E has validated the robustness of this assay. We conclude that our newly developed system will facilitate the discovery of GPCR ligands.

Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling.

G protein-coupled receptors (GPCRs) play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling. Thus, endocytic GPCR behavior has a significant impact on various aspects of physiology. In this study, we developed a novel GPCR internalization assay to facilitate characterization of endocytic GPCR behavior. We genetically engineered chimeric GPCRs by fusing HaloTag (a catalytically inactive derivative of a bacterial hydrolase) to the N-terminal end of the receptor (HT-GPCR). HaloTag has the ability to form a stable covalent bond with synthetic HaloTag ligands that contain fluorophores or a high-affinity handle (such as biotin) and the HaloTag reactive linker. We selectively labeled HT-GPCRs at the cell surface with a HaloTag PEG ligand, and this pulse-chase covalent labeling allowed us to directly monitor the relative number of internalized GPCRs after agonist stimulation. Because the endocytic activities of GPCR ligands are not necessarily correlated with their agonistic activities, applying this novel methodology to orphan GPCRs, or even to already characterized GPCRs, will increase the likelihood of identifying currently unknown ligands that have been missed by conventional pharmacological assays.