Epidemiology and Risk Factors of Eosinophilic Esophagitis in Japan: A Population-Based Study.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) has been increasingly diagnosed globally. However, there have been few general population-based studies in Asia. The aim of this study was to investigate EoE epidemiology in the Japanese general population. METHODS: We analyzed an employer-based health insurance claim database from January 2005 to September 2022. EoE cases were identified on the basis of the International Statistical Classification of Diseases and Health-related Problems, 10th Revision code, K20.0. We calculated the incidence and prevalence of EoE using Poisson regression and binomial distribution, respectively. Using 10 matched controls for each EoE case, a nested case-control study was performed to identify potential risk factors for EoE. RESULTS: Of 15,200,895 individuals, 1010 EoE cases were identified. The incidence and prevalence of EoE were 2.82 (95% confidence interval [CI], 2.44-3.26) per 100,000 person-years and 10.68 (95% CI, 10.01-11.37) per 100,000 people in 2022, nearly 3 and 8 times as high as those in 2017, respectively. Smoking was associated with decreased risk of EoE (odds ratio [OR], 0.45, 0.36-0.56, P < .001), whereas alcohol consumption (OR, 1.51, 1.21-1.88, P < .001) was associated with increased risk of EoE along with several allergic conditions and psychiatric disorders. EoE was not related to either body mass index or lifestyle-related diseases such as hypertension, diabetes mellitus, hyperuricemia, and dyslipidemia. CONCLUSIONS: The incidence and prevalence of EoE in Japan have steadily increased over the past 2 decades. Nevertheless, EoE remains less common in Japan compared with the United States and Western Europe. Factors contributing to the epidemiology of EoE on a global basis may improve our understanding of the contribution of genetic and environmental risk factors.

Evaluating the association of body mass index with COVID-19 severity and mortality using Japanese administrative claims data.

INTRODUCTION: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population. METHODS: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group. RESULTS: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality. CONCLUSION: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population.

Immune Checkpoint Inhibitor Is Associated with Improved Survival in Advanced Non-small Cell Lung Cancer Occurring in Patients with Autoimmune Disease.

The use of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, clinical trials often exclude those with a history of autoimmune diseases (ADs) because of concerns regarding immune-related adverse events. Therefore, the efficacy of ICIs in advanced NSCLC patients with ADs should be evaluated. This study used administrative claims data from advanced treatment centers in Japan and identified patients with advanced NSCLC who began chemotherapy between December 2016 and January 2023. The patients were divided into four groups based on the presence of ADs and types of chemotherapy received. The association between ICI therapy and overall survival in the subgroups with or without ADs, and the association between the presence of AD and overall survival in patients who received ICI therapy and conventional chemotherapy, were analyzed using Cox proportional hazard regression, including therapy and presence of ADs and their interaction as covariates. These results were obtained using the inverse probability of treatment weighting. ICI therapy had a hazard ratio (95% confidence interval) for death in the subgroup of AD and non-AD patients of 0.88 (0.84-0.92) and 0.83 (0.71-0.97), respectively (p = 0.459 for interaction). For some specific ADs, including type 1 diabetes mellitus, the association between ICI therapy and decreased mortality was not observed. In conclusion, our study showed comparable associations between ICI therapy and reduced mortality in AD and non-AD subgroups of patients with advanced NSCLC. However, therapy strategies tailored to each AD type and thorough discussions regarding the risk-benefit profile are crucial.

Seasonal variations for newly prescribed urate-lowering drugs for asymptomatic hyperuricemia and gout in Japan.

Background: Urate-lowering drugs (ULDs) have been approved for treatment of asymptomatic hyperuricemia and gout in Japan. Although serum urate levels and rates of gout onset are known to have seasonal variations, no survey results regarding the seasonality of ULD prescriptions for asymptomatic hyperuricemia and gout have been reported. Methods: A large-scale database of medical claims in Japan filed between January 2019 and December 2022 was accessed. In addition to total size of the recorded population for each month examined, the numbers of patients every month with newly prescribed ULDs for asymptomatic hyperuricemia and gout were noted, based on the International Classification of Diseases, 10th Revision, codes E79.0 and M10. Results: The results identified 201,008 patients with newly prescribed ULDs (median age 49.0 years, male 95.6%). Of those, 64.0% were prescribed ULDs for asymptomatic hyperuricemia and 36.0% for gout. The proportion of new ULD prescriptions was seasonal, with that significantly (p < 0.001) higher in summer (June-August) [risk ratio (RR) 1.322, 95% CI 1.218 to 1.436] and autumn (September-November) (RR 1.227, 95% CI 1.129-1.335) than in winter (December-February), whereas the proportion in spring (March-May) was not significantly different from winter. There was no significant difference after stratification by drug type (uric acid production inhibitor/uricosuric agent) or size of the medical institution, nor subgrouping by age or sex (p for interaction = 0.739, 0.727, 0.886, and 0.978, respectively). On the other hand, the proportions of new ULD prescriptions for asymptomatic hyperuricemia were significantly lower and for gout significantly higher in spring than winter, while those were similar in summer and autumn for both groups (p for interaction<0.001). Conclusion: The present findings indicate that new prescriptions for ULDs to treat asymptomatic hyperuricemia or gout in Japan show seasonal differences, with higher rates noted in summer and autumn as compared to winter.

Lack of Association Between Immunotherapy and Improvement of Survival for Non-small Cell Lung Cancer Patients With Hemodialysis: A Nationwide Retrospective Cohort Study.

BACKGROUND: The number of patients undergoing hemodialysis continues to increase globally, and the incidence of cancer is high among these patients. Immune checkpoint inhibitors are widely used in patients with advanced cancer, especially non-small cell lung cancer (NSCLC); however, their effectiveness in hemodialysis patients is poorly documented. METHODS: This retrospective cohort study used data from a nationwide database. Patients diagnosed with NSCLC, undergoing hemodialysis, and who started chemotherapy between September 2008 and January 2023 were included. In the intention to treat (ITT) analysis, patients were divided into immune checkpoint inhibitor (ICI) and conventional chemotherapy group, and in the chronological analysis, patients were divided into 2 groups before and after ICI approval. Overall survival (OS) was analyzed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards analyses. A propensity score approach was applied to address confounding factors, and analyses were performed by weighting each patient with the inverse of the estimated propensity score. RESULTS: We identified 322 and 389 patients in the ITT and chronological analyses respectively. In both analyses, there were no notable difference of OS between 2 groups (P values by log-rank test 0.933 and 0.248, respectively). The hazard ratios for OS were 0.980 (95% confidence interval [CI]: 0.678-1.415) in the ITT analysis and 0.805 (95% CI: 0.531-1.219) in the chronological analysis. CONCLUSION: The ICI treatment and approval were not significantly associated with improvement of survival in patients with NSCLC undergoing hemodialysis.

Treatment sequencing after failure to alectinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Alectinib is the first-line therapy for anaplastic lymphoma kinase-positive non-small-cell lung cancer. Although some guidelines have recommended using other anaplastic lymphoma kinase inhibitors after alectinib failure, evidence for such regimens in patients who fail to respond to alectinib is limited. This study involved using administrative claims data from acute care hospitals in Japan. We extracted the data of 634 patients diagnosed with lung cancer between September 1, 2014, and January 31, 2023, who received alectinib treatment before treatment with another anaplastic lymphoma kinase inhibitor. We assessed distributions of patients according to their treatment sequencing and prognosis among three periods defined based on the initial marketing dates of lorlatinib and brigatinib. The type of anaplastic lymphoma kinase inhibitors after alectinib failure changed over time. In the most recent period, lorlatinib (58%) and brigatinib (40%) became predominant. Two-year overall survival improved over time (47%-84%), accompanied by an increased 2-year proportion of patients who continuously used anaplastic lymphoma kinase inhibitors after alectinib failure (13%-44%). The times to treatment discontinuation of the regimen between patients treated with lorlatinib and brigatinib were similar, with a hazard ratio of 1.02 (95% confidence interval, 0.64-1.64) in the period after marketing brigatinib. This study provides insights into the evolving treatment landscape for patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer who experience failed alectinib treatment and highlights the need for further studies and data accumulation to determine the optimal treatment strategy.

Renin-angiotensin-aldosterone system inhibitors are associated with improved paclitaxel-induced peripheral neuropathy in lung cancer: a study using administrative claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients' quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin-angiotensin-aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN). METHODS: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine-Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding. RESULTS: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762-0.929). The result was consistent in various sensitivity analyses and important subgroup analyses. CONCLUSIONS: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer.

Association of plasma xanthine oxidoreductase activity with vascular endothelial function independent of serum uric acid level: MedCity21 health examination registry.

Background: Xanthine oxidoreductase (XOR) inhibitor administration, known to reduce uric acid and reactive oxygen species (ROS) production, also improves vascular endothelial function (VEF). This cross-sectional study examined our hypothesis that XOR contributes to impaired VEF through ROS but not uric acid production. Methods: In 395 subjects (196 males, 199 females) without urate-lowering agent administration who underwent a health examination, plasma XOR activity was determined using our highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. For VEF evaluation, flow-mediated dilatation (FMD) in the brachial artery was determined by ultrasound, with physical and laboratory measurements also obtained. Results: The median values for plasma XOR activity, serum uric acid, and FMD were 26.6 pmol/h/mL, 5.4 mg/dL, and 6.2%, respectively. Simple regression analysis showed weak correlations of both log plasma XOR activity and serum uric acid level with FMD (r = -0.213, p < 0.001 and r = -0.139, p = 0.006, respectively). However, multivariable linear regression analyses revealed that log plasma XOR activity but not serum uric acid level remained associated with FMD (ß = -0.116, p = 0.037 and ß = 0.041, p = 0.549, respectively) after adjustments for various clinical parameters, with no remarkable inconsistencies for the association observed in subgroups divided based on sex or uric acid level. Finally, a series of mediation analyses showed that serum uric acid level did not meet the criteria for mediator of the association of plasma XOR activity with FMD (p = 0.538). Conclusions: These findings suggest the possibility that XOR contributes to the pathophysiology of impaired VEF through ROS but not uric acid production.

Inflammation Related to Association of Low Uric Acid and Progression to Severe Disease in Patients Hospitalized for Non-Severe Coronavirus Disease 2019.

Uric acid has antioxidant properties. To examine whether a low uric acid level is associated with severe coronavirus disease 2019 (COVID-19) progression via inflammation, alveolar damage, and/or coagulation abnormality, a retrospective observational study of 488 patients with non-severe COVID-19 and serum uric acid level ≤7 mg/dL at admission was conducted. Serum C-reactive protein (CRP), serum Krebs von den Lungen 6 (KL-6), and plasma D-dimer levels were also measured as markers of inflammation, alveolar damage, and coagulation abnormality, respectively. Median values for uric acid, CRP, KL-6, and D-dimer at admission were 4.4 mg/dL, 3.33 mg/dL, 252.0 U/mL, and 0.8 µg/mL, respectively. Among the total cohort, 95 (19.5%) progressed to severe COVID-19 with a median (interquartile range) time of 7 (4-14) days. Multivariable Cox proportional hazards regression analysis showed that low uric acid level was associated with a higher rate of severe COVID-19 progression. However, uric acid level was inversely associated with CRP level, and the association between the level of uric acid and severe COVID-19 progression was significantly different with and without CRP level inclusion. In contrast, no such association was found for KL-6 or D-dimer level. Low uric acid may contribute to severe COVID-19 progression via increased inflammation in subjects without hyperuricemia.

Reduced Risk of Progression from Non-Severe to Severe COVID-19 in Hospitalized Dialysis Patients by Full COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) vaccination reduces the risk of progression to severe COVID-19 in the general population. To examine that preventive effect in dialysis patients, the association of vaccination status with severe COVID-19 progression was investigated in this retrospective observational study conducted from December 2020 to May 2022 of 100 such patients hospitalized for non-severe COVID-19 at Inoue Hospital (Suita, Japan). Fifty-seven were fully vaccinated, defined as receiving a COVID-19 vaccine second dose at least 14 days prior to the onset of COVID-19, while 43 were not. Among all patients, 13 (13.0%) progressed to severe COVID-19 with a median (interquartile range) time of 6 (2.5-9.5) days, while 87 (87.0%) were discharged after 11 (8-16) days. Kaplan-Meier analysis showed that fully vaccinated patients had a significantly lower rate of progression to severe COVID-19 (p = 0.001, log-rank test). Cox proportional hazard analysis also indicated that full COVID-19 vaccination was significantly associated with reduced instances of progression to severe COVID-19 (hazard ratio 0.104, 95% confidence interval 0.022 to 0.483; p = 0.004) after balancing patient background characteristics using an inverse probability of treatment weight method. These results suggest that full vaccination status contributes to reducing the risk of progression from non-severe to severe COVID-19 in dialysis patients.