Group of longitudinal adverse event patterns after the fourth dose of COVID-19 vaccination with a latent class analysis.

Introduction: Vaccination has been implemented as a useful measure to combat the COVID-19 pandemic. However, there is a tendency for individuals to avoid vaccination due to the possibility of adverse events, making it important to investigate the relationship between COVID-19 vaccines and their adverse events. This study explored longitudinal adverse event patterns and factors that influence adverse events following the second to fourth doses of the COVID-19 vaccine through a latent class analysis. Methods: Participants were recruited from the Fukushima Prefecture and included individuals who had completed four doses of the COVID-19 mRNA vaccine. This study utilized data from questionnaire surveys and blood collection conducted between September 2021 and November 2022. In the questionnaire, factors such as sex, age, medical history, medication, type of vaccine administered, and adverse events following vaccination were recorded. Additionally, in the blood data, serological tests [IgG(S)] and cellular immune responses (T-spot) were measured. Descriptive statistics, latent class analysis, multivariable logistic regression, and multiple regression analyses were performed to identify the longitudinal adverse event patterns and influencing factors. By analyzing adverse events over time, we identified two distinct groups: those less prone to experiencing adverse events (Group 1) and those more susceptible (Group 2) to latent class analysis. Results: A total of 1,175 participants were included after excluding those without any adverse events. The median age of the participants in Group 1 was 70 years, and in Group 2 it was 51 years. The proportion of female participants was 298 in Group 1 and 353 in Group 2. Patients in Group 2 were significantly younger (p < 0.001) and more likely to be female (p < 0.001) than those in Group 1. Furthermore, the median IgG(S) value after the fourth vaccination was 3,233 AU/mL in Group 1 and 4,059.39 AU/mL in Group 2. The median T-spot value was 15.4 in Group 1 and 28.5 in Group 2. Group 2 showed significantly higher IgG(S) and T-spot values after the fourth vaccination (p < 0.001). Discussion: Our findings suggest that factors other than age, particularly sex and a history of allergies, significantly influence the likelihood of experiencing adverse events. Groups categorized by latent class analysis for longitudinal adverse events are expected to be valuable for optimizing vaccination strategies and formulating public health measures.

Health Information Seeking on the Internet Among Patients With and Without Cancer in a Region Affected by the 2011 Fukushima Triple Disaster: Cross-Sectional Study.

BACKGROUND: Health information seeking via the internet among patients with cancer in disaster-affected areas is underresearched. OBJECTIVE: This study aims not only to assess the extent and means of web-based health information seeking among patients with cancer living in the disaster-affected area of the 2011 Fukushima triple disaster but also to compare these patterns with those without cancer, identifying distinct and shared factors influencing their web-based health information behaviors. METHODS: We surveyed 404 patients (263 with and 141 without cancer) from the surgery department outpatient office at Minamisoma Municipal General Hospital, from October 2016 to January 2017. The survey included self-administered questions on internet and digital device use. Descriptive analyses were performed to examine the use patterns of digital devices and the internet and their impact on health information seeking across different age groups of patients with and without cancer. Multivariable logistic regression was used to examine factors associated with web-based health information seeking, stratifying by cancer diagnosis. RESULTS: The proportion of participants who sought health information on the internet was comparable between patients with cancer and patients without cancer (19% vs 17.4%; P=.71). Digital device use varied significantly with age, with peak smartphone use occurring among the youngest cohorts for both groups. Multivariable logistic regression revealed that patients with cancer using smartphones or tablets daily were significantly more likely to gather web-based health information (odds ratio [OR] for smartphones 3.73, 95% CI 1.58-8.80; OR for tablets 5.08, 95% CI 1.27-20.35). Trust in institutional websites also significantly influenced web-based health information gathering among patients with cancer (OR 2.87, 95% CI 1.13-7.25). Conversely, among patients without cancer, unemployment was associated with a lower likelihood of seeking web-based health information (OR 0.26, 95% CI 0.08-0.85), whereas trust in both institutional and personal websites significantly increased this likelihood (OR for institutional websites 6.76, 95% CI 2.19-20.88; OR for personal websites 6.97, 95% CI 1.49-32.58). CONCLUSIONS: This study reveals that a small proportion of both patients with cancer and patients without cancer engage in health information seeking via the internet, influenced by age, digital device use, and trust in institutional websites. Given the growing prevalence of digital literacy, strategies to enhance accessible and reliable web-based health information should be developed, particularly for patients with cancer in postdisaster settings. Future efforts should focus on tailored health communication strategies that address the unique needs of these populations.

Continued cancer drug approvals in Japan and Europe after market withdrawal in the United States: A comparative study of accelerated approvals.

Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross-sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug-indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment.

Spectral and HPLC Analyses of Synthesized Butin and Butein.

Butin and butein are significant bioactive flavanones derived from plants, existing as tautomers of each other. However, their physicochemical attributes, such as their spectral profiles under varying experimental conditions in aqueous solutions and established chromatographic methods for distinguishing between them, remain undetermined. In this study, we determined the basic properties of butin and butein using conventional spectroscopic, reversed-phase, and chiral HPLC analyses. The spectra of the synthesized butin and butein were analyzed using a UV-Vis spectrophotometer in several solvents with different polarities as well as in aqueous solutions at various pH values. Furthermore, the behavior of the measured spectra was reproduced by calculations to reveal the effects of the solvent and pH on the spectra of butin and butein in organic and aqueous solutions. Subsequently, we assessed the structural stability of butin and butein using reversed-phase HPLC, which revealed that butein is unstable compared with butin in a general culture medium. The synthesized butin was effectively separated into R- and S-isomers with positive and negative Cotton effects, respectively, via HPLC using a chiral column. These findings will aid in uncovering the individual properties of both butin and butein that may have been concealed by their tautomerism and enable the synthesis of S-butin, which is typically challenging and time-consuming to isolate.

Long-term evacuation and obesity: a 12-year follow-up comparative study of residents inside and outside Katsurao Village after the Fukushima nuclear disaster.

Objective: Evacuation, owing to a disaster, impacts various aspects of an individual's life, including health status. This study aimed to determine the prevalence of obesity among residents of Katsurao Village, Fukushima Prefecture, after the evacuation order due to the Fukushima nuclear disaster in 2011 was lifted in 2016 and to compare the prevalence of obesity by place of residence (inside or outside the village). Methods: The number of examinees, sex, age, place of residence, body mass index (BMI), exercise habits, smoking habits, drinking habits, and dietary status were extracted from the results of health checkups since 2016. We compared the BMI of the indigenes of Katsurao Village by place of residence (inside or outside the village) over time. Results: Although 7 years have passed since 2016, ~70% of the registered residents of Katsurao Village still live outside the village. The obesity rates have consistently been higher among people living outside the village compared to those inside, and the place of residence was the only factor significantly associated with obesity. Conclusion: The findings of this study suggest early intervention is necessary to prevent health risks associated with disaster evacuation if the evacuation period is prolonged.

Unveiling, Analyzing the Mechanisms of, and Proposing Solutions for Bribery in Japan's Medical Device Sector.

Both public and academic scrutiny of the financial relationships between the medical device industry and the healthcare society occur less frequently than those involving the pharmaceutical industry, and Japan is no exception to these shortcomings. This paper examines the ethical and legal challenges inherent in Japan's medical device industry through the lens of bribery scandals, placing these issues within the broader context of global healthcare corruption. It aims to derive lessons and suggest universal strategies for ethical and legal enhancements. The discussion includes two notable cases: one involving inappropriate transactions between a cancer center and a biliary stent manufacturer, and another concerning a corrupt donation scheme between a medical device company and a university's anesthesiology department, which was found guilty. In our analysis, we also acknowledge the industry's efforts toward compliance and reform to maintain a balanced perspective. The analysis not only highlights the unique culture and structure of the Japanese medical device industry, such as the exploitation of flexible pricing and opaque financial practices but also contrasts these issues with the tightly regulated pharmaceutical industry. This approach reveals both sector-specific challenges and common corruption drivers, enhancing our understanding of why such scandals occur and persist. We propose ethical and compliance-focused business measures such as centralizing donation decisions, limiting the financial independence of marketing divisions, and increasing transparency, alongside adopting mandatory disclosure practices based on successful models from the United States and Europe. By emphasizing integrity and presenting diverse perspectives, this study aims to elevate ethical and legal standards in the medical device industry and improve patient health outcomes worldwide.

The difficulty of nuclear emergency prevention measures during natural disasters: ongoing challenges in Japan.

It is crucial to anticipate nuclear emergency scenarios and implement effective measures. Japan's climate and topography make it vulnerable to natural disasters; thus, it is necessary to address compounding and cascading disaster scenarios involving the simultaneous occurrence of natural and nuclear disasters. On 1 January 2024, an earthquake hit the Noto region of Ishikawa Prefecture, resulting in damage to the area around the Shika Nuclear Power Plant, located 90 km from the epicenter. This earthquake revealed that, in the event of a complex disaster, it is possible that residents living within 30 km of the Shika Nuclear Power Plant will be completely unprepared for a nuclear disaster. In the event of a complex disaster, it is crucial to implement appropriate countermeasures while balancing responses to both nuclear and natural disasters and optimizing radiation disaster prevention measures.

Parental Knowledge and Attitudes Towards Helicobacter Pylori Screening in Adolescents: A School-Based Questionnaire Study Among Guardians of Junior High School Students in Yokosuka City, Japan.

PURPOSE: Helicobacter pylori (HP) infection, a risk factor for gastric cancer, is prevalent in Japan. Consequently, some municipalities across Japan are implementing HP screening and treatment programs for adolescents. However, little is known about parents' attitudes and awareness regarding HP screening for their children. This study aimed to elucidate parental perspectives on HP screening for their children and identify the factors influencing these attitudes. METHODS: This study focused on the parents of first-year junior high school students in Yokosuka City, Kanagawa Prefecture, where an HP screening and treatment program had been implemented for adolescents. The survey questionnaire was distributed among parents in all 23 public junior high schools in Yokosuka City. RESULTS: Among the 618 respondents, 86.4% supported HP screening for their children. Regression analysis identified sufficient knowledge about HP (adjusted odds ratio (aOR) = 5.80; 95% confidence interval (CI), 2.10-16.03) and being in their 40s (aOR = 2.25; 95% CI, 1.35-3.77) as significant factors influencing supportive attitudes. For parents favoring the screening, common reasons included perceiving it as a promising opportunity (53.2%) and considering the test necessary (44.0%). In contrast, those who opposed screening frequently cited it as unnecessary (66.7%) or believed that their children did not have HP. CONCLUSIONS: A significant proportion of parents in Yokosuka City, Japan, demonstrated a good understanding of HP and expressed a high level of interest in HP screening for their children. Further investigation of parents' attitudes is essential for the effective implementation of adolescent HP screening programs.

Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.

Association Between Gender and Payments Received From Pharmaceutical Companies Among Medical Professors and Associate Professors in Japan.

Introduction While prior research showed gender gaps in industry payments for medical professionals in the United States, there are limited data in Japan. So, this study seeks to investigate the potential gender gap in the receipt of pharmaceutical companies (PFCs) across all medical fields in Japan. Based on the results of previous studies, we developed a hypothesis that male doctors get more PFC than female doctors. Materials and methods Data from 92 pharmaceutical companies in Japan, covering 2016 to 2019, were analyzed. The analysis was conducted on professors and associate professors at all national and public medical universities in Japan, with gender as a factor variable and payments as an outcome variable, and variables that may have influenced the factor or outcome variables in previous studies, such as specialization, university type, region, rank and years since graduation, as control variables. Payments were converted to US dollars using the December 31, 2021, rate of 115 yen to the dollar for comparison purposes. Results Out of 1,825 subjects, 1,755 were males and 70 females. Males consistently received higher median payments from pharmaceutical companies (PFCs) than females across categories. In particular, among physicians specializing in internal medicine, the median PFC for men was $25 compared to $8 for women. For physicians affiliated with former imperial universities (the seven former imperial universities founded before World War II), the median PFC for men was $32 compared to $5 for women. Multivariate analysis confirmed significantly higher total benefits for males from 2016 to 2019, with the gender gap widening during this period (incidence rate ratio (IRR) for 2016: 0.51, IRR for 2019: 0.44). Conclusions Japanese male professors and associate professors received significantly higher PFCs than their female counterparts, and this gender gap expanded from 2016 to 2019, highlighting persistent gender inequality in the medical field in Japan, similar to trends observed in the United States.

Understanding Reasons for Vaccination Hesitancy and Implementing Effective Countermeasures: An Online Survey of Individuals Unvaccinated against COVID-19.

This online survey of unvaccinated people living in Japan aimed to identify the reasons for declining vaccination and to develop effective countermeasures. We conducted a hierarchical class analysis to classify participants, examine factors influencing their classification, and provide the information they needed about coronavirus disease 2019 (COVID-19) and trusted sources of COVID-19 information for each group. A total of 262 participants were classified into three groups: Group 1 with no specific reason (28 participants, 10.69%); Group 2 with clear concerns about trust in the vaccine (85 participants, 32.44%), and Group 3 with attitudinal barriers, such as distrust of the vaccine and complacency towards COVID-19, and structural barriers, such as vaccination appointments (149 participants, 56.87%). For each group, females tended to be classified in Group 2 more than Group 1 (Odds ratio (OR) [95% confidential intervals (95%CI)] = 1.64 (0.63 to 2.66), p = 0.001) and in Group 3 more than Group 1 (OR [95%CI] = 1.16 (0.19 to 2.12), p = 0.019). The information that the participants wanted to know about COVID-19 was different among each group (Safety: p < 0.001, Efficacy: p < 0.001, Genetic effects: p < 0.001). Those who did not receive the COVID-19 vaccine also had lower influenza vaccination coverage (8.02%). Additionally, 38 participants (14.50%) were subject to social disadvantages because they had not received the COVID-19 vaccine. Countermeasures should be carefully tailored according to the target population, reasons for hesitancy, and specific context. The findings of this study may help develop individualized countermeasures to address vaccine hesitancy.

Two-Year-Span Breast Cancer Screening Uptake in Japan after the COVID-19 Pandemic and Its Association with the COVID-19 Vaccination.

There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6110 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29-0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62-0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship.

Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling.

Osteoblast adherence to bone surfaces is important for remodeling bone tissue. This study demonstrates that deficiency of TG-interacting factor 1 (Tgif1) in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matrices in vitro. Furthermore, Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (Pak3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased Pak3 expression, which impairs osteoblast spreading. Additionally, Tgif1 is implicated in osteoblast recruitment and activation of bone surfaces in the context of bone regeneration and in response to parathyroid hormone 1-34 (PTH 1-34) treatment in vivo in mice. These findings provide important novel insights in the regulation of the cytoskeletal architecture of osteoblasts.

Using the geriatric nutritional risk index to predict outcomes in older patients with remnant gastric cancer after gastrectomy: a retrospective multicenter study in Japan.

PURPOSE: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). METHODS: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. CONCLUSIONS: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC.

Assistive AI in Lung Cancer Screening: A Retrospective Multinational Study in the United States and Japan.

Purpose To evaluate the impact of an artificial intelligence (AI) assistant for lung cancer screening on multinational clinical workflows. Materials and Methods An AI assistant for lung cancer screening was evaluated on two retrospective randomized multireader multicase studies where 627 (141 cancer-positive cases) low-dose chest CT cases were each read twice (with and without AI assistance) by experienced thoracic radiologists (six U.S.-based or six Japan-based radiologists), resulting in a total of 7524 interpretations. Positive cases were defined as those within 2 years before a pathology-confirmed lung cancer diagnosis. Negative cases were defined as those without any subsequent cancer diagnosis for at least 2 years and were enriched for a spectrum of diverse nodules. The studies measured the readers' level of suspicion (on a 0-100 scale), country-specific screening system scoring categories, and management recommendations. Evaluation metrics included the area under the receiver operating characteristic curve (AUC) for level of suspicion and sensitivity and specificity of recall recommendations. Results With AI assistance, the radiologists' AUC increased by 0.023 (0.70 to 0.72; P = .02) for the U.S. study and by 0.023 (0.93 to 0.96; P = .18) for the Japan study. Scoring system specificity for actionable findings increased 5.5% (57% to 63%; P < .001) for the U.S. study and 6.7% (23% to 30%; P < .001) for the Japan study. There was no evidence of a difference in corresponding sensitivity between unassisted and AI-assisted reads for the U.S. (67.3% to 67.5%; P = .88) and Japan (98% to 100%; P > .99) studies. Corresponding stand-alone AI AUC system performance was 0.75 (95% CI: 0.70, 0.81) and 0.88 (95% CI: 0.78, 0.97) for the U.S.- and Japan-based datasets, respectively. Conclusion The concurrent AI interface improved lung cancer screening specificity in both U.S.- and Japan-based reader studies, meriting further study in additional international screening environments. Keywords: Assistive Artificial Intelligence, Lung Cancer Screening, CT Supplemental material is available for this article. Published under a CC BY 4.0 license.

Nature and Trend of Pharmaceutical Payments to Japanese Board-Certified Neurologists Between 2016 and 2019: A Pre-emergence Analysis Amidst the Development of Next-Generation Alzheimer's Disease Drugs.

OBJECTIVE: There is insufficient data on the financial relationships between Japanese neurologists and pharmaceutical companies prior to the advent of new-generation Alzheimer's disease drugs. The purpose of this study is to evaluate the magnitude, prevalence, and trend of the financial relationship between Japanese neurologists and pharmaceutical companies between 2016 and 2019. METHODS: A cross-sectional study was undertaken to evaluate the financial relationships between all board-certified neurology specialists and pharmaceutical companies in Japan from 2016 and 2019. Descriptive statistics were applied to measure the magnitude and prevalence of payments among specialists, as well as their trends during the study periods. RESULTS: In a four-year analysis, 77 pharmaceutical companies disbursed a total of USD 36,869,204 across 50,050 payments to 2,696 neurologists in Japan, revealing a mean payment of USD 10,809 per specialist. Notably, the Gini index of 0.997 indicated a high inequality in payment distribution, with a minority of specialists receiving a substantial proportion of payments. Trends displayed irregularities, but an overall increase in total payments from 2016 to 2019, with a significant contribution from the top 10 pharmaceutical companies accounting for 74.2% of total payments, with Takeda Pharmaceutical and Eisai Company notably increasing payments in 2019. There were notable geographical variations in neurologist and payment distribution across 47 prefectures. CONCLUSION: Our analysis of neurologist payments from pharmaceutical companies in Japan showed a substantial financial relationship with overall increases, yearly varied increments, and payment inequality. Caution is warranted as financial ties may intensify with the continued development of next-generation Alzheimer's disease drugs.