Increasing trends of pharmaceutical payments to breast cancer specialists in Japan: A retrospective study from 2016 to 2019.

INTRODUCTION: The introduction of new drugs often leads to aggressive promotion and potential financial conflicts of interest, which may bias treatment decisions and potentially harm patients. The breast cancer therapeutics market is rapidly evolving globally, and Japan is no exception. This study aimed to analyze trends in pharmaceutical payments to breast cancer specialists in Japan from 2016 to 2019, focusing on company-level data, relationships with new drug introductions, and individual specialist payment patterns. METHODS: This retrospective study examined financial relationships between pharmaceutical companies and breast cancer specialists in Japan from 2016 to 2019. The analysis focused on certified specialists as of May 2023 and used payment data from 93 pharmaceutical companies for activities such as lecturing, writing, and consulting. First, a company-level analysis examined total payments, categories, and trends for all companies and the top 10 individually; second, a specialist-level analysis looked at payment amounts amount and counts. The Gini index was employed to assess the concentration of payments among specialists. RESULTS: Total payments reached USD 13,329,911, growing at 10.1% annually, with 81.4% allocated to lecturing engagements. The top 10 companies, led by Chugai Pharmaceutical, Eisai, and AstraZeneca, accounted for 89.5% of all payments. Companies like Pfizer Japan and Eli Lilly Japan saw notable increases following the introduction of new drugs such as palbociclib and abemaciclib. Payment distribution was highly skewed, with an average of $7,692 per specialist but a median of only $2,884. A Gini index of 0.994 further confirmed that a small group of specialists received a disproportionately large share of the payments. CONCLUSION: From 2016 to 2019, pharmaceutical payments to Japanese breast cancer specialists increased significantly, coinciding with new drug introductions. The concentration of payments among a select group of specialists raises concerns about potential influences on clinical decision-making and guideline recommendations.

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.

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.

Case Report: Difficulties faced by a home oxygen therapy patient who died after the Fukushima Daiichi nuclear power plant accident.

Following the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi nuclear power plant accident in 2011, mandatory evacuation orders were issued to residents living near the nuclear power plant in Fukushima prefecture, including some patients receiving home oxygen therapy. Although the vulnerability of patients with home oxygen therapy (one of the population groups most vulnerable to disasters) has been noted, there is little information on the health effects of evacuation in the event of a radiation disaster. A 90-year-old man diagnosed with chronic obstructive pulmonary disease since the age of 70, and lived in a town located approximately 20 km south of the nuclear power plant, died 8 months after the disaster due to worsening health conditions. This case reveals the potential for both physical and psychological burdens experienced by vulnerable groups like patients undergoing home oxygen therapy during evacuations in times of disaster. Although it is only a case report and the information is limited, severe respiratory distress requiring home oxygen therapy may present a significant risk factor for disaster-related deaths, especially in cases where evacuations are prolonged, such as in nuclear disasters. Due to the challenge of obtaining prompt public support immediately after a disaster, home oxygen therapy patients may need to prioritize self-help and mutual assistance in their disaster preparedness efforts.

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.

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.

Primary care clinic visits in formerly evacuated areas due to radiation disaster following the Great East Japan Earthquake: A retrospective descriptive study.

Radiation disasters pose distinctive medical challenges, requiring diverse care approaches. Beyond radiation exposure assessment, addressing health impacts due to lifestyle changes, especially among vulnerable populations, is vital. Evacuation orders issued in radiation-affected areas introduce unique healthcare dynamics, with their duration significantly influencing the recovery process. Understanding evolving patient demographics and medical needs after lifting evacuation orders is crucial for post-disaster care planning. Minamisoma Municipal Odaka Hospital, located 13 to 20 km from Fukushima Daiichi Nuclear power plant in a post-evacuation zone, was greatly affected by the Great East Japan Earthquake and subsequent radiation disaster. Data were retrospectively collected from patient records, including age, gender, visit date, diagnoses, and addresses. Patient records from April 2014 to March 2020 were analyzed, comparing data before and after the July 2016 evacuation order lift. Data was categorized into pre and post-evacuation order lifting periods, using International Classification of Diseases, Tenth Edition codes, to identify the top diseases. Statistical analyses, including χ-square tests, assessed changes in disease distributions. Population data for Odaka Ward and Minamisoma City fluctuated after lifting evacuation orders. As of March 11, 2011, Odaka Ward had 12,842 residents (27.8% aged 65+ years), dropping to 8406 registered residents and 2732 actual residents by April 30, 2018 (49.7%). Minamisoma City also saw declines, with registered residents decreasing from 71,561 (25.9%) to 61,049 (34.1%). The study analyzed 11,100 patients, mostly older patients (75.1%), between 2014 and 2020. Post-lifting, monthly patient numbers surged from an average of 55.2 to 213.5, with female patients increasing from 33.8% to 51.7%. Disease patterns shifted, with musculoskeletal cases declining from 23.8% to 13.0%, psychiatric disorders increasing from 9.3% to 15.4%, and trauma-related cases decreasing from 14.3% to 3.9%. Hypertension (57.1%) and dyslipidemia (29.2%) prevailed post-lifting. Urgent cases decreased from 1.3% to 0.1%. This study emphasizes the importance of primary care in post-evacuation zones, addressing diverse medical needs, including trauma, noncommunicable diseases, and psychiatric disorders. Changing patient demographics require adaptable healthcare strategies and resource allocation to meet growing demands. Establishing a comprehensive health maintenance system tailored to these areas' unique challenges is crucial for future disaster recovery efforts.

Pneumocystis Pneumonia in Locally Advanced Breast Cancer Despite Prophylactic Use of Trimethoprim-Sulfamethoxazole During Prednisolone Treatment for a Pembrolizumab-Induced Immune-Related Adverse Event: A Case Report.

Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.

Surgical productivity recovery after the COVID-19 pandemic in Japan.

Introduction: Previous studies demonstrated that the surgical productivity regressed in 2020. This study therefore explored whether the COVID-19 pandemic had any significant lasting effect of reducing the surgical productivity in Japan. This is a retrospective observational study which is an extension of the previous ones. Methods: The authors analyzed 18,805 surgical procedures performed during the study period from April 1 through September 30 in 2016-22. A non-radial and non-oriented Malmquist model under the variable returns-to-scale assumptions was employed. The decision-making unit (DMU) was defined as a surgical specialty department. Inputs were defined as (1) the number of assistants, and (2) the surgical duration. The output was defined as the surgical fee. The study period was divided into 42 one-month periods. The authors added all the inputs and outputs for each DMU during these study periods, and computed its Malmquist index, efficiency change and technical change. The outcome measures were its annual productivity, efficiency, and technical changes between the same months in each year. Results: There was no statistically significant difference in annual productivity, efficiency, and technical changes between pre-pandemic and post-pandemic periods. Discussion: No evidence was found to suggest that the COVID-19 pandemic has any significant lasting effect of reducing the surgical productivity.

Predicting CKD progression using time-series clustering and light gradient boosting machines.

Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2. Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m2; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m2; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m2; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m2; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m2). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m2.

Long-term Experience on Breast Cancer-related Lymphedema in the Coastal Area of Fukushima, Japan After the 2011 Triple Disaster.

BACKGROUND/AIM: Disasters can jeopardize breast cancer care and Japan's triple disaster in 2011 (earthquake, tsunami, and nuclear accident) is no exception. However, detailed information is lacking regarding the care of breast cancer related lymphedema (BCRL) following the disaster. We aimed to explore the process by which local patients become aware of BCRL, the problems faced, and the support they require. We also aimed to clarify the effects of the 2011 disaster on experiences related to lymphedema in the target population. PATIENTS AND METHODS: Patients who developed BCRL after breast cancer treatment were recruited from Iwaki city, a municipality located in the southern coastal region of Fukushima (N=16). In-depth, semi-structured, face-to-face interviews were conducted, and the obtained data were appraised using thematic analysis. RESULTS: Five themes related to BCRL were identified: 1) the process of becoming aware of BCRL, 2) troubles or worries/concerns due to BCRL, 3) information sources regarding BCRL management, 4) strategies to cope with BCRL, and 5) the adverse impacts of the 2011 disaster on BCRL management. CONCLUSION: Except for the disaster context, the themes are in line with those of previous studies conducted in the non-disaster context. Nonetheless, there were limited but non-negligible adverse effects of the 2011 disaster on long-term local BCRL management. The findings of this study demonstrate the necessity for individualizing coping strategies against BCRL among healthcare professionals in the Fukushima coastal area and beyond.

Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

Small vessel platelet thrombosis in the peripheral nerves in POEMS syndrome.

INTRODUCTION/AIMS: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M-protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. METHODS: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. RESULTS: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. DISCUSSION: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin-12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder.