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Importance: The resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the prognostic significance of ECG in clinical practice settings., Objective: To investigate the association between ECG abnormalities and CVD outcomes in a working-age population., Design, Setting, and Participants: This nationwide cohort study included individuals aged 35 to 65 years from the Japan Health Insurance Association database, which covers approximately 40% (30 million) of the working-age population in Japan. Data from April 1, 2015, to March 31, 2022, were included, and analysis was conducted from October 1, 2022, to April 11, 2024., Exposures: Baseline ECG status (normal, 1 minor abnormality, ≥2 minor abnormalities, or major abnormality)., Main Outcomes and Measures: The primary outcome was a composite of overall death and CVD hospital admission due to myocardial infarction, stroke, or heart failure. The secondary outcome was developing a new major ECG abnormality over the years of screening., Results: Of 3 698 429 individuals enrolled in the nationwide annual health check program (mean [SD] age, 47.1 [8.5] years; 66.6% male), 623 073 (16.8%) had 1 minor ECG abnormality, 144 535 (3.9%) had 2 or more minor ECG abnormalities, and 56 921 (1.5%) had a major ECG abnormality. During a median follow-up of 5.5 (IQR, 3.4-5.7) years, baseline ECG abnormality was independently associated with an increased incidence of the composite end points of overall death and CVD admission compared with normal ECG (incidence rates per 10 000 person-years: 92.7 [95% CI, 92.2-93.2] for normal ECG, 128.5 [95% CI, 127.2-129.9] for 1 minor ECG abnormality, 159.7 [95% CI, 156.6-162.9] for ≥2 minor ECG abnormalities, and 266.3 [95% CI, 259.9-272.3] for a major ECG abnormality; adjusted hazard ratios: 1.19 [95% CI, 1.18-1.20] for 1 minor ECG abnormality, 1.37 [95% CI, 1.34-1.39] for ≥2 minor ECG abnormalities, and 1.96 [95% CI, 1.92-2.02] for a major ECG abnormality). Furthermore, the presence and number of minor ECG abnormalities were associated with an increased incidence of developing new major ECG abnormalities (incidence rates per 10 000 person-years: 85.1 [95% CI, 84.5-85.5] for normal ECG, 217.2 [95% CI, 215.5-219.0] for 1 minor ECG abnormality, and 306.4 [95% CI, 302.1-310.7] for ≥2 minor ECG abnormalities; and adjusted hazard ratios: 2.52 [95% CI, 2.49-2.55] for 1 minor ECG abnormality and 3.61 [95% CI, 3.55-3.67] for ≥2 minor ECG abnormalities). Associations were noted regardless of baseline CVD risk., Conclusions and Relevance: The findings of this study suggest that the potential role of routine ECG screening for early prevention of CVD events, along with the optimal follow-up strategy, should be examined in future studies.

Purpose: This study evaluated the risk of metachronous colorectal cancer (CRC) after resection of index (first) rectal cancer in patients with Lynch syndrome (LS)., Methods: Clinicopathological data of patients with genetically proven LS were retrospectively analyzed in this multicenter Japanese study. The cumulative incidence of metachronous CRC and the overall survival were compared between patients with index rectal cancer (rectal group) and those with index colon cancer (colon group)., Results: The median age at index CRC surgery was lower in the rectal group than in the colon group (37 vs. 46 years old, P = 0.01). The cumulative 5-, 10-, and 20-year incidences of metachronous CRC were 3.5%, 13.9%, and 21.1%, respectively, in the rectal cancer group and 14.9%, 22.0%, and 57.9%, respectively, in the colon cancer group (P = 0.02). The overall survival curves were not significantly different between two groups (P = 0.23)., Conclusion: This is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS., (© 2024. The Author(s).)

Because of its superior safety profile and improved outcomes, trans-radial percutaneous coronary intervention (TRI) has become the preferred access in percutaneous coronary intervention (PCI) of native coronary disease. This study investigated the impact of TRI on in-hospital outcomes after PCI for coronary artery bypass graft vessels (GV-PCI). We analyzed patients who underwent GV-PCI in 2019-2022 from the Japanese nationwide registry. Patients were categorized into the TRI and trans-femoral PCI (TFI) groups. We assessed the association between TRI and in-hospital outcomes. The primary outcome was a composite of in-hospital death and major bleeding. In this study, 2,295 patients were analyzed.. The primary outcomes occurred in 29 patients (1.3%), including 17 deaths (0.7%). Major bleeding occurred in 12 patients (0.5%), and access site bleeding in 7 patients (0.3%). The TRI group (n = 1,521) showed lower crude rates of the primary outcome (0.9% vs 1.9%, p = 0.039), major bleeding (0.3% vs 1.0%, p = 0.027), and access site bleeding (0.1% vs 0.6%, p = 0.047) compared with the TFI group (n = 774). Univariable logistic regression demonstrated a significant association of TRI with reduced primary outcome (odd ratio [OR] 0.47, 95% confidence interval [CI] 0.22 to 0.98), major bleeding (OR 0.25, 95% CI 0.07 to 0.80), and access site bleeding (OR 0.20, 95% CI 0.03 to 0.94). In the multivariable analysis, TRI was still significantly associated with a decrease in major bleeding events (OR 0.29, 95% CI 0.07 to 0.93). In conclusion, the use of TRI was associated with a reduction in bleeding events when referenced to TFI in the context of GV-PCI., Competing Interests: Declaration of competing interest Dr. Kohsaka reports a relationship with Bristol-Myers Squibb, Pfizer, Novartis, and AstraZeneca that includes: funding grants and speaking and lecture fees. Dr. Ishii reports a relationship with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Kowa, Novartis, Nippon Boehringer Ingelheim, Otsuka Pharma, Pfizer, Mochida Pharma, and Tanabe Mitsubishi that includes: speaking and lecture fees. Dr. Amano reports a relationship with Astellas Pharma, AstraZeneca, Bayer, Daiichi Sankyo, and Bristol-Myers Squibb that includes: speaking and lecture fees. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: One of the disadvantages of medical documentation in Electronic Medical Record (EMR) systems is that records tend to be redundant by "copying and pasting", a writing style to duplicate and revise previous records. In this study, we analyzed the similarity between records to identify the factors affecting the writing style of clinical notes., Method: We analyzed 98,038 records of 4,149 patients from two years in the Department of Obstetricians and Gynecology at Kyoto University Hospital, Japan. We observed the correlation between the distribution of the record similarity and string amounts, as well as the disease codes and ratios of outpatient visit., Results: The patient group with high record similarity and large number of strings was the group with reproductive medicine, followed by the group of malignant tumor follow-up or Women's Healthcare., Discussion: In reproductive medicine, physicians have a demand for an overarching evaluation, and in follow-up malignancies or in Women's Healthcare, they have a demand to check for subtle differences from the last time. These facts along with our data insist that the writing style in EMR systems is related to the patient's status., Conclusion: We declared that the writing style in EMR systems is affected by the patient's status. The writing style of duplicating and revising is preferred (1) when there is a clinical demand for an overarching evaluation, and (2) when there is a clinical demand to check for subtle differences from the last time.

Despite the perceived advantages of health information exchange (HIE), their utilization has been stagnant, and a detailed survey at the regional level is needed to address this issue. We conducted interviews with operators of HIEs in operation in Japan as a pilot study and found that subjective descriptions by healthcare professionals contained in clinical notes are frequently referenced in HIEs. Currently, however, only a limited number of medical institutions in Japan disclose subjective descriptions. In this study, we aim to clarify the factors that influence whether or not to disclose subjective descriptions through an interview survey. Although the final results are yet to be determined, it is anticipated that the non-disclosing medical institutions will show negative aspects of disclosure, such as privacy concerns and misuse of information. Addressing the concerns raised in this study is important for the future dissemination of HIE.

Cataract surgery outcomes in centenarian patients have not previously been explored. This study aimed to examine characteristics and report clinical results of people aged ≥100 years undergoing cataract surgery. This was a retrospective observational study, including patients aged ≥100 years who underwent cataract surgery between 2003 and 2021 at Miyata Eye Hospital in Japan. Medical charts were reviewed for information on cataract severity, surgery type, anesthesia, as well as ocular and medical comorbidities. Using Mann-Whitney test, visual acuity, intraocular pressure, and corneal endothelial cell density were compared before and after surgery. Eight eyes of 5 patients were included in the study (mean age, 101.5 ± 1.2 years). Seven of these eyes (87.5%) belonged to women. All surgeries were performed under topical anesthesia using phacoemulsification and insertion of the intraocular lens fixed in the bag. All patients had multiple preoperative medical comorbidities; however, there were no intraoperative, postoperative ocular, or general complications. The postoperative best-corrected visual acuity was significantly improved compared to that before surgery (1.18 ± 0.74 and 0.29 ± 0.52, respectively, P = .004). Neither intraocular pressure nor corneal endothelial cell density demonstrated a significant difference postoperatively. Cataract surgery can be safely performed under topical anesthesia in centenarians without complications using proper perioperative medical control and preparation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder., Methods: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34; mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored., Results: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis, were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying antirheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively., Conclusions: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Because exacerbation of severe asthma decreases patients' quality of life, this study aimed to identify predictive factors for asthma exacerbation., Methods: Japanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program)., Results: A total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51-72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV 1 (%FEV 1 ) at enrollment were 204 (IQR, 49-436)/μL, 28 (IQR, 15-43) ppb, 172 (IQR, 56-473) IU/mL, and 80.0 (IQR, 61.1-96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV 1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period., Conclusions: Exacerbation during the previous year, low ACT score, and low %FEV 1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor., Competing Interests: Declaration of competing interest HH has received grants from Novartis Pharma K.K., outside the submitted work. AK received speaker fees from AstraZeneca K.K., GlaxoSmithKline K.K., Novartis Pharma K.K., and Sanofi K.K., NM received speaker fees from AstraZeneca K.K., Boehringer Ingelheim K.K., GlaxoSmithKline K.K., Novartis Pharma K.K., and Sanofi K.K.. The rest of the authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for adult T-cell leukaemia/lymphoma (ATL). Specific HLAs are associated with outcomes of immunotherapy and allo-HSCT. We hypothesised that individual HLAs would affect the clinical outcomes of ATL patients after allo-HSCT. Using data from a Japanese registry, we retrospectively analysed 829 patients with ATL who received transplants from HLA-identical sibling donors or HLA-A, -B, -C or -DRB1 allele-matched unrelated donors between 1996 and 2015. We evaluated the overall mortality risk of HLA-A, -B and -DR antigens with frequencies exceeding 3%. Outcomes were compared between transplants with or without specific HLA antigens. Of the 25 HLAs, two candidates were identified but showed no statistically significant differences by multiple comparison. HLA-B62 was associated with a lower risk of mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.51-0.90; p = 0.008), whereas HLA-B60 was associated with a higher risk of mortality (HR, 1.64; 95% CI: 1.19-2.27; p = 0.003). In addition, HLA-B62 was associated with a lower risk of transplant-related mortality (TRM) (HR, 0.52; 95% CI: 0.32-0.85, p = 0.009), whereas HLA-B60 was associated with a higher risk of grades III-IV acute graft-versus-host disease (HR, 2.63; 95% CI: 1.62-4.27; p < 0.001). Neither HLA influenced relapse. The higher risk of acute GVHD in HLA-B60-positive patients and the lower risk of TRM in HLA-B62-positive patients were consistent with previously obtained results from patients with other haematological malignancies. Consideration of HLA in ATL patients may help to predict risk and outcomes after allo-HSCT., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To assess the accuracy of intraocular lens (IOL) power formulas, namely, SRK/T, Haigis, Barrett Universal II, Barrett True-K for keratoconus, Kane formula, and Kane formula for keratoconus, for cataract with keratoconus in Japanese eyes., Setting: Five surgical sites in Japan., Design: A retrospective case series., Methods: Eyes with keratoconus undergoing cataract surgery were included. Postoperative refraction was compared with the prediction by the formulas. Visual acuity, manifest spherical equivalent, prediction error (PE), and mean absolute errors (MAEs) were determined 1 month postoperatively. The PE within 0.50 diopter (D), 1.00 D, and 2.00 D were compared between IOL formulas. Subgroup analysis based on the steepest keratometry (stage 1, ≤ 48 D; stage 2, > 48 D and ≤ 53 D; and stage 3, > 53 D) was performed. The relationship between PE and preoperative biometric data were assessed., Results: Fifty eyes were included. The MAE of the Barrett True-K for keratoconus, Kane keratoconus, and Kane formulas were significantly lower than that of Haigis. A statistically significant difference in the prediction accuracy within ± 0.50 D was found between Kane keratoconus and Haigis. The prediction accuracy of the Barrett True-K for keratoconus, SRK/T, and Kane within ± 1.00 D was statistically significant compared with that of Haigis. In stage 3, the Barrett True-K for keratoconus had a significantly lower MAE than SRK/T and Haigis., Conclusion: Keratoconus-specific formulas were more accurate than existing formulas in Japanese eyes. The Barrett True-K formula for keratoconus had higher prediction accuracy in severe keratoconus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The coronavirus disease 2019 (COVID-19) pandemic exhibited several different waves threatening global health care. During this pandemic, medical resources were depleted. However, the kind of medical resources provided to each wave was not clarified. This study aimed to examine the characteristics of medical care provision at COVID-19 peaks in preparation for the next pandemic., Methods: Using medical insurance claim records in Japan, we examined the presence or absence of COVID-19 infection and the use of medical resources for all patients monthly by age group., Results: The wave around August 2021 with the Delta strain had the strongest impact on the working population in terms of hospital admission and respiratory support. For healthcare providers, this peak had the highest frequency of severely ill patients. In the subsequent wave, although the number of patients with COVID-19 remained high, they were predominantly older adults, with relatively fewer patients receiving intensive care., Conclusions: In future pandemics, we should refer to the wave around August 2021 as a situation of medical resource shortage resulting from the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukuyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The use of rehabilitation after arthroplasty in Japan is unknown. We aimed to identify utilization of postoperative rehabilitation after total hip arthroplasty (THA) and to explore the factors associated with rehabilitation usage., Design: A retrospective cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB)., Setting: Hospitals nationwide., Participants: Patients aged >40 years who underwent primary THA between 2017 and 2018 (N=51,332)., Interventions: Not applicable., Main Outcome Measures: The proportion of patients who underwent postoperative rehabilitation and the number of rehabilitation days were also calculated. Patient demographic characteristics, hospital case volumes, and regions associated with continuing postoperative rehabilitation were analyzed using a Cox proportional hazards model., Results: Eligible patients were selected from 3033 hospitals, of whom 41,192 (80%) were women. Of these, 94% used inpatient rehabilitation, and 20% received outpatient rehabilitation. The mean durations of rehabilitation were 47±72 days for inpatient and 195±109 days for outpatient, respectively. Large-scale hospitals performing more than 200 procedures annually had the shortest duration of inpatient rehabilitation (36-65 days) and the longest duration of outpatient rehabilitation (220-109 days) compared with smaller hospitals. The regression model consistently showed that rehabilitation continued longer at hospitals with over 200 patients per year (HR 0.96, 95% CI 0.93-0.99, P<.007)., Conclusion: The Japanese health care system provided higher access to inpatient rehabilitation after THA than other countries. One limitation of this study is that long-term care insurance data were not analyzed. However, outpatient rehabilitation vary according to hospital case volume. Further research is needed to determine the causes of variation in rehabilitation use and the effect of variation on patient outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to evaluate the short-term outcomes of pancreatoduodenectomy (PD) in older individuals., Methods: Data from the Japanese Diagnosis Procedure Combination database on 62 275 patients who underwent PD from 1 April 2012 to 31 March 2020 were analyzed. Patients were divided into five age groups: <70, 70-74, 75-79, 80-84, and ≥85 years. The associations between postoperative outcomes and age were investigated using multilevel analysis. The mean differences in length of hospital stay and cost were also compared., Results: The rate of PD in older individuals increased annually. Compared with the youngest age group (< 70 years), the incidence rate ratios for in-hospital mortality were 1.52 (95% confidence interval [CI]: 1.30-1.76), 2.07 (1.82-2.37), 2.29 (1.94-2.71), and 2.92 (2.20-3.87) in the 70-74, 75-79, 80-84, and ≥ 85-year-old age groups, respectively (all p < .001). Postoperative complications, length of postoperative hospital stay, and cost increased significantly with increasing age., Conclusions: These real-world data emphasize the higher levels of morbidity, mortality, and cost in older patients. Careful attention should be paid when considering the indication for PD in older individuals., (© 2023 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Coronavirus disease 2019 (COVID-19) affects both life and health. However, the differentiation from other types of pneumonia and effect of kidney disease remains uncertain. This retrospective observational study investigated the risk of in-hospital death and functional decline in ≥ 20% of Barthel Index scores after COVID-19 compared to other forms of pneumonia among Japanese adults, both with and without end-stage kidney disease (ESKD). The study enrolled 123,378 patients aged 18 years and older from a national inpatient administrative claims database in Japan that covers the first three waves of the COVID-19 pandemic in 2020. After a 1:1:1:1 propensity score matching into non-COVID-19/non-dialysis, COVID-19/non-dialysis, non-COVID-19/dialysis, and COVID-19/dialysis groups, 2136 adults were included in the analyses. The multivariable logistic regression analyses revealed greater odds ratios (ORs) of death [5.92 (95% CI 3.62-9.96)] and functional decline [1.93 (95% CI 1.26-2.99)] only in the COVID-19/dialysis group versus the non-COVID-19/non-dialysis group. The COVID-19/dialysis group had a higher risk of death directly due to pneumonia (OR 6.02, 95% CI 3.50-10.8) or death due to other diseases (OR 3.00, 95% CI 1.11-8.48; versus the non-COVID-19/non-dialysis group). COVID-19 displayed a greater impact on physical function than other types of pneumonia particularly in ESKD., (© 2024. The Author(s).)

Background: Patients with familial adenomatous polyposis (FAP) have an increased risk of developing gastric neoplasms. However, the clinical course of FAP with these gastric lesions has not yet been fully clarified. The present study aimed to clarify the changes in the incidence risk of developing gastric adenoma or gastric cancer during the lifespan of patients with FAP., Methods: Four hundred forty-three patients with data regarding gastric adenoma and gastric cancer retrospectively registered in a nationwide Japanese multicenter study were enrolled. The cumulative incidences and hazard rates (HRs) of gastric neoplasms were evaluated., Results: The cumulative incidence rates in 50-year-old patients with FAP were 22.8% for gastric adenoma and 7.6% for gastric cancer, respectively. No significant association was found between gastric neoplasms and the colonic phenotype. The peak age for the HR of gastric adenoma was 65 years, with the highest HR (0.043). Regarding the incidence of gastric cancer, the HR increased moderately up to the age of 40 years, but the increase accelerated from the age of 50 years (HR = 0.0067)., Conclusion: Careful surveillance of the upper gastrointestinal tract in elderly patients with FAP, such as shortening the interval of follow-up according to age, may be helpful for early diagnosis of gastric cancer., (© 2024. The Author(s).)

Background: Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs. Introduction of a physicochemical assay for GmS is needed to help ensure its quality and quantity., Objective: This study aimed to develop quality control measures for GmS that could be complementary to quantitative assays and purity tests specified in the JP., Methods: For each gentamicin C component (C1, C2, and C1a), theoretical potencies were determined based on the quantitative relationship between purity and potency, as measured by quantitative 1H NMR and microbiological assays, respectively. Two lots of the JP reference standard (RS) were used as test samples, with the contents of each component and impurity (sisomicin and garamine) being determined using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS)., Results: The ratios of theoretical potency for C1, C2, and C1a were 1.00, 1.21, and 1.80, respectively. The potencies of the GmS JP RSs, which were estimated based on the contents and theoretical potency of each C component, corresponded well with those determined through microbiological assays. Marked differences in impurities (%) between the two RS lots were highlighted by quantifying sisomicin and garamine., Conclusions: The developed analytical procedure enabled the characterization of two different JP RSs in terms of content ratio, potencies, and impurities., Highlights: Novel analytical procedures useful for routine quality control of GmS were developed using HILIC-MS/MS., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients., Methods: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps., Results: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants., Conclusions: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Guidance/guidelines on drug-drug interactions (DDIs) have been issued in Japan, the United States, and Europe. These guidance/guidelines provide decision trees for conducting metabolizing enzyme-mediated clinical DDI studies; however, the decision trees for transporter-mediated DDIs lack quantitative prediction methods. In this study, the accuracy of a net-effect mechanistic static pharmacokinetics (MSPK) model containing the fraction transported (f t ) of transporters was examined to predict transporter-mediated DDIs. This study collected information on 25 oral drugs with new active reagents that were used in clinical DDI studies as perpetrators (42 cases) from drugs approved in Japan between April 2016 and June 2020. The AUCRs (AUC ratios with and without perpetrators) of victim drugs were predicted using the net-effect MSPK model. As a result, 83 and 95% of the predicted AUCRs were within 1.5- and 2-fold error in the observed AUCRs, respectively. In cases where the victims were statins in which pharmacokinetics several transporters are involved, 70 and 91% of the predicted AUCRs were within 1.5- and 2-fold errors, respectively. Therefore, the net-effect MSPK model was applicable for predicting the AUCRs of victims, which are substrates for multiple transporters., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (© 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

Background: The 3rd edition of the evidence-based clinical practice guidelines for gastroesophageal reflux disease (GERD) 2021 from the Japanese Society of Gastroenterology states that the treatment strategy for potassium-competitive acid blocker (PCAB)-refractory GERD remains unclear. Furthermore, even if GERD improves with the administration of an acid secretion inhibitor, it is feared that GERD may flare up after discontinuation of the drug, resulting in some cases in which patients are forced to take vonoprazan semipermanently (the so-called PCAB-dependent cases). From a global perspective, PCAB is not yet used in all countries and regions, and measures that can be taken now for cases in which a conventional proton pump inhibitor (PPI) is inadequately effective need to be devised., Summary: Endoscopic treatment for GERD may be effective in cases where conventional proton pump inhibitors are ineffective; however, there are insufficient long-term studies to corroborate this, and its cost effectiveness is unknown. Other treatment options for PCAB or PPI-refractory GERD include surgical procedures (Nissen and Toupet operations), which have a longer history than endoscopic treatment for GERD. However, their long-term results are not as good as those of acid secretion inhibitors, and they are not cost effective. Endoscopic treatment for GERD may fill gaps in inadequate surgical treatment. In April 2022, endoscopic anti-reflux mucosal resections (ARMS [anti-reflux mucosectomy] and ESD-G [endoscopic submucosal dissection for GERD]) were approved for reimbursement, making endoscopic treatment of GERD possible throughout Japan., Key Messages: It is important to identify the background factors in cases in which endoscopic treatments are effective., (© 2023 S. Karger AG, Basel.)

Background: It is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data., Methods: This was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021., Results: The mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years., Conclusions: The results suggest that the early detection of breast cancer may reduce medical care costs at the patient level., (© 2023. The Author(s).)

Background: Despite increasing incidences of hypertension, recent trends in mortality and urgent dialysis following acute hypertension (AHT) remain undetermined., Methods: This retrospective observational cohort study evaluated 50 316 hospitalized AHT patients from 2010 to 2019, using an administrative claims database in Japan. We examined trends in incidence, urgent dialysis, mortality, and its risk factors using Poisson regression models. Using International Classification of Disease and Related Health Problems, 10th Revision codes, AHT was categorized into 5 spectrums: malignant hypertension ( n =1792), hypertensive emergency ( n =17 907), hypertensive urgency ( n =1562), hypertensive encephalopathy ( n =6593), and hypertensive heart failure (HHF; n =22 462)., Results: The median age of the patients was 76 years, and 54.9% were women. The total AHT incidence was 70 cases per 100 000 admission year. The absolute death rate increased from 1.83% (95% CI, 1.40-2.40) to 2.88% ([95% CI, 2.42-3.41]; Cochran-Armitage trend test, P< 0.0001). Upward trends were observed in patients aged ≥80, with lean body mass index ≤18.4, and with HHF. Urgent dialysis rates increased from 1.52% (95% CI, 1.12-2.06) to 2.60% (2.17-3.1; Cochran-Armitage trend test; P =0.0071) in 48 235 patients, excluding maintenance dialysis patients. Older age, men, lean body mass, malignant hypertension, HHF, and underlying chronic kidney disease correlated with higher mortality risk; greater hospital volume correlated with lower mortality risk; and malignant hypertension, HHF, diabetes, chronic kidney disease, and scleroderma correlated with a higher risk of urgent dialysis., Conclusions: Mortality and urgent dialysis rates following AHT have increased. Aging, complex comorbidities, and HHF-type AHT contributed to the rising trend of mortality., Competing Interests: Disclosures None.

Background: We evaluated the risk of metachronous colorectal cancer (mCRC) and explored the optimal extent of colectomy in patients with Lynch syndrome (LS) and first colon cancer (fCC) in Japan, where the extent of colectomy for colon cancer (CC) is shorter than that in Western countries., Methods: The clinicopathologic and survival data of patients with LS who developed CC were collected from a nationwide database and analyzed retrospectively. The cumulative incidence of mCRC after actual segmental colectomy was compared with that of mCRC when more extensive colectomy was assumed., Results: There were 142 eligible patients (65 female). The median age at fCC surgery was 46.5 (range: 14-80) years. The cumulative incidence of 5-, 10-, and 20-year mCRC rate was 13.4%, 20.8%, and 53.6%, respectively. The incidence was higher in the left-sided group (splenic flexure to rectosigmoid colon, n = 54) than in the right-sided group (cecum to transvers colon, n = 88) (66.3% vs. 45.3% in 20 years, P < 0.01). Assuming that all patients would have undergone hemicolectomy or total colectomy, the estimated mCRC risk was 41.5% and 9.4% (P < 0.01, vs. actual procedures), respectively. The 20-year overall survival rate of all the patients was 83.3% without difference by fCC sidedness (P = 0.38)., Conclusions: To reduce the incidence of mCRC, patients with genetically diagnosed LS and fCC, preferentially located in the left-sided colon, may need to undergo more extended colectomy than that usually performed in Japan. However, such extended colectomy should be counterbalanced with favorable overall survival and actual risk of mCRC development., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: The purpose of this study was to investigate the association between subjective built environment and the onset of frailty in older adults living in the community. In addition, we examined whether daily walking time, depressive symptoms, and social support from neighbors and friends are mediating factors., Design: This was a longitudinal study using prospective cohort data from the 2013 Japan Gerontological Evaluation Study., Setting and Participants: Participants included 38,829 older adults who were not frail recruited from 22 cities and towns., Methods: The dependent variable, frailty, was assessed using the Kihon checklist. The explanatory variables were 5 items for the subjective built environment. The mediating variables were walking time of at least 30 minutes per day, a Geriatric Depression Scale (GDS) score of at least 5 points, and social support from neighbors and friends. We performed a causal mediation analysis of mediating effects between each built environment and frailty onset. Furthermore, the proportion of mediation was estimated., Results: After 3 years of follow-up, frailty emerged in 2232 adults (6.7%) in 2016. Access to parks and sidewalks, access to fresh food stores, houses or facilities where people feel free to drop in, and fascinating views, or buildings reduced the onset of frailty. Mediators significantly associated with the built environment and onset of frailty were access to parks and sidewalks (walking time: 5.9%, GDS: 22.9%, social support: 5.9%), access to fresh food stores (GDS: 31.9%, social support: 4.0%), hills and steps (GDS: 20.6%), houses or facilities where people feel free to drop in (walking time: 4.0%, GDS 28.0%, social support: 10.4%), and fascinating views, or buildings (walking time: 7.8%, GDS: 42.1%, social support: 12.0%)., Conclusions and Implications: We found that walking time, depression, and social support were mediating factors in the relationship between built environment and the onset of frailty., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Surgical site infections (SSI) are associated with increased morbidity and mortality rates. This study aimed to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery Real-world data collected from 16 university hospitals in Japan were reviewed. The medical records of consecutive 2782 patients (1750 men and 1032 women) who underwent abdominal surgery under general anesthesia at 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. SSI were observed in 275 patients (incidence rate:9.9%), and POM was administered to 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists classification, surgical site, preoperative Prognostic Nutritional Index score, POM, extent of surgery, operation time, and intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U test, P < .01). Multivariate analysis revealed that POM had significant preventive effects against postoperative SSI (estimate: -0.245, standard error: 0.080, P < .01). Surgical site, American Society of Anesthesiologists classification, and operation time were also significant and independent clinical predictors of SSI. The analysis of real-world data from 16 university hospitals revealed that, regardless of the content and degree of the problem, the addition of POM has significant beneficial effects in reducing the risk of SSI in patients who undergo abdominal surgery. Medical records from each hospital and data from the Health Care Payment Fund were collected and analyzed retrospectively., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Immunity is known to persist after vaccination for varicella zoster virus, but the duration of immunity in patients who develop herpes zoster (HZ) remains unknown. To investigate the association between a past history of HZ and its occurrence in the general population. The Shozu HZ (SHEZ) cohort study included data for 12 299 individuals aged ≥50 years with information on their HZ history. Cross-sectional and 3-year follow-up studies were carried out to analyze the associations between a history of HZ (yes <10 years, yes ≥10 years, no) and the proportion of positive varicella zoster virus skin test results (erythema diameter ≥5 mm) and the risk of HZ after adjusting for potential confounding factors including age, sex, body mass index, smoking status, sleep duration, and mental stress. The incidences of positive skin test results were 87.7% (470/536) for individuals with a history of HZ <10 years ago, 82.2% (396/482) for those with a history of HZ ≥10 years, and 80.2% (3614/4509) for those with no history of HZ. The multivariable odds ratios (95% confidence intervals) of erythema diameter ≥5 mm were 2.07 (1.57-2.73) and 1. 39 (1.08-1.80) for individuals with a history <10 years and ≥10 years ago, respectively, compared with no history. The corresponding multivariable hazard ratios of HZ were 0.54 (0.34-0.85) and 1.16 (0.83-1.61), respectively. A past history of HZ <10 years ago may reduce the occurrence of HZ., (© 2023 Japanese Dermatological Association.)

Japan has implemented a cluster-based approach for coronavirus disease 2019 (COVID-19) from the pandemic's beginning based on the transmission heterogeneity (overdispersion) of severe acute respiratory coronavirus 2 (SARS-CoV-2). However, studies analyzing overdispersion of transmission among new variants of concerns (VOCs), especially for Omicron, were limited. Thus, we aimed to clarify how the transmission heterogeneity has changed with the emergence of VOCs (Alpha, Delta, and Omicron) using detailed contact tracing data in Yamagata Prefecture, Japan. We estimated the time-varying dispersion parameter ([Formula: see text]) by fitting a negative binomial distribution for each transmission generation. Our results showed that even after the emergence of VOCs, there was transmission heterogeneity of SARS-CoV-2, with changes in [Formula: see text] during each wave. Continuous monitoring of transmission dynamics is vital for implementing appropriate measures. However, a feasible and sustainable epidemiological analysis system should be established to make this possible., (© 2023. Springer Nature Limited.)

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents., Competing Interests: Declaration of competing interest Issei Tokimatsu received research funding from Asahi Kasei Pharma Corporation, and scholarship donations from Shionogi & Co., Ltd., and Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., and Pfizer Japan Inc. Makoto Miki hold shares in Daiichi Sankyo Co., Ltd., and received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Tomotaro Wakamura is an employee of Sumitomo Pharma Co., Ltd. Daisuke Kurai received research funding from Daiichi Sankyo Co., Ltd., and scholarship donations from Shionogi & Co., Ltd. Hiroki Tsukada received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Nobuki Aoki received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Hiroshige Mikamo received speaker honoraria from Nippon Becton Dickinson Company, Ltd., Astellas Pharma Inc., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Pfizer Japan Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co., Ltd., Gilead Sciences K.K., Saraya Co., Ltd., Tsumura & Co., Meiji Seika Pharma Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., Fukoku Co., Ltd., GlaxoSmithKline K.K., Kowa Company, Ltd., research funding from Fukoku Co., Ltd., Sekisui Medical Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., Saraya Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Roche Diagnostics K.K., ASKA Pharmaceutical Co., Ltd., Tosoh Corporation, Bruker Japan K.K., Abbott Diagnostics Medical Co., Ltd., Ortho Clinical Diagnostics K.K., Kyorin Pharmaceutical Co., Ltd., and scholarship donations from Asahi Kasei Pharma Co., Shionogi & Co., Ltd., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fukoku Co., Ltd., and Morii Co., Ltd. Atsushi Nakamura received speaker honoraria from Kyorin Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. Akira Ukimura received scholarship donations from Shionogi & Co., Ltd. Hiroshi Kakeya received speaker honoraria from MSD K.K., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Shionogi & Co., Ltd., Asahi Kasei Pharma Corporation., Astellas Pharma Inc., and Pfizer Japan Inc. Katsunori Yanagihara received speaker honoraria from Daiichi Sankyo Co., Ltd., MSD K.K., Astellas Pharma Inc., and Taisho Pharma Co., Ltd. (formerly Taisho Toyama Pharmaceutical Co., Ltd.), research funding from Fujifilm Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd., and scholarship donations from Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Kyorin Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: We aimed to investigate the association between repetitive proteinuria and cardiovascular events among the middle-aged and older general Japanese population., Design: Retrospective cohort study., Setting: We used repeated health screening results and medical claim data from one of the largest health insurers in Japan., Participants: Among the middle-aged and older participants (40-74 years, n=179 840), 90 752 were excluded for undergoing health screening fewer than two times and 344 were excluded for having a history of cardiovascular diseases; 88 744 who underwent kidney function screenings at least two times (from April 2011 to March 2015) were included in the analysis. Based on dipstick proteinuria test results, the participants were divided into 'Repetitively-positive' (positive two times or more (positive proteinuria was defined as≥1+)), 'Once-positive' and 'All-negative' groups., Primary and Secondary Outcome Measures: The primary outcome of major cardiovascular events from baseline screening to June 2021 was hospitalisation or death due to acute myocardial infarction (AMI), cerebrovascular diseases, heart failure (HF) or peripheral vascular diseases (PVDs). The association between proteinuria and major cardiovascular events was assessed using a Cox proportional hazards model., Results: Of the 88 744 participants, 8775 (9.9%) and 5498 (6.2%) had Once-positive and Repetitively-positive proteinuria, respectively. During the follow-up period of 402 799 person-years (median 5.25 years), 660 cardiovascular events were observed, with an incidence of 1.64 per 1000 person-years (95% CI 1.52 to 1.77). Despite adjusting for major cardiovascular risk factors, we observed a high incidence of cardiovascular events in the Repetitively-positive (HR 2.08, 95% CI 1.67 to 2.59) and Once-positive groups (HR 1.36, 95% CI 1.07 to 1.72). We found similar associations for AMI, cerebrovascular disease, HF and PVD., Conclusions: Proteinuria is often repeatedly detected during annual renal screening in the general population. Repetitive proteinuria is a risk factor for major cardiovascular events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heart failure is common and is associated with high rates of hospitalization. Home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in Japan in 2006 and 2012, respectively., Objective: This study aimed to examine the effect of post-discharge care by conventional or enhanced HCSCs on readmission, compared with general clinics., Design: Retrospective cohort study using the Japanese nationwide health insurance claims database., Participants: Participants were ≥65 years of age, admitted for heart failure and discharged between July 2014 and August 2015 and received a home visit within a month following the discharge (n=12,393)., Main Measures: The exposure was the type of medical facility that provides post-discharge home healthcare: general clinics, conventional HCSCs, and enhanced HCSCs. The primary outcome was all-cause readmission for 6 months after the first visit; the incidence of emergency house calls was a secondary outcome. We used a competing risk regression using the Fine and Gray method, in which death was regarded as a competing event., Key Results: At 6 months, readmissions were lower in conventional (38%) or enhanced HCSCs (38%) than general clinics (43%). The adjusted subdistribution hazard ratio (sHR) of readmission was 0.87 (95% CI: 0.78-0.96) for conventional and 0.86 (0.78-0.96) for enhanced HCSCs. Emergency house calls increased with conventional (sHR: 1.77, 95% CI:1.57-2.00) and enhanced HCSCs (sHR: 1.93, 95% CI: 1.71-2.17)., Conclusions: Older Japanese patients with heart failure receiving post-discharge home healthcare by conventional or enhanced HCSCs had lower readmission rates, possibly due to compensation with more emergency house calls. Conventional and enhanced HCSCs may be effective in reducing the risk of rehospitalization. Further studies are necessary to confirm the medical functions performed by HCSCs., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective　This study aimed to qualitatively analyze changes in the health status and factors affecting technical intern trainees over time during their first year in Japan and examined the necessary support for healthy living.Methods　The study targeted sixteen technical intern trainees who had been living in Japan for almost four months. The study was conducted quarterly in a year, using semi-structured interviews to measure physical and mental health conditions, injury or illness, subjective symptoms, and training and daily life conditions. Dietary content was assessed using photographs taken by participants. Health-check results were collected when available. Data were classified into the six components of the International Classification of Functioning, Disability and Health (ICF), and further qualitative data were analyzed inductively for health-affecting factors using qualitative longitudinal analysis.Results　The types and timing of illnesses, injuries, subjective symptoms, and health-affecting factors varied. Stress and concerns were experienced by more than 56.3% of each study's participants and more than 44.4% had the possibility of a mood or anxiety disorder. The participants with heavy labor had musculoskeletal disorders in the first half of the study period. The health-check results were in Japanese and some participants did not fully understand them. Fifteen categories were extracted as health-affecting factors:《sleeping conditions》,《joy of independence and anxiety》,《decreased vitality and fatigue》,《undertaking the training》,《communication skills and efforts to learn Japanese》,《efforts for self-health care》,《adaptation to Japanese lifestyle》,《leisure and interaction with Japanese people》,《religious activities》,《training environment》,《living environment》,《support from friends, family and workplace》,《natural environment and economic trends》,《saving-oriented lifestyle》, and《motive for coming to Japan and self-evaluation after one year》.Conclusion　The technical intern trainees experienced various physical and psychological symptoms. Support in maintaining and promoting positive aspects of health-affecting factors and removing negative aspects is important for the health of trainees. In addition, it is important to support the improvement of the health literacy of trainees by offering information on exercise facilities and medical institutions providing health-check services in multiple languages, and improving means of communications through cooperation with related organizations and the use of regular channels by trainees. Furthermore, involving healthcare professionals in "regional councils" is necessary.

Breakthrough candidemia (BrC) is a significant problem in immunocompromised patients, particularly those with hematological disorders. To assess the characteristics of BrC in patients with hematologic disease treated with novel antifungal agents, we collected clinical and microbiological information on said patients from 2009 to 2020 in our institution. Forty cases were identified, of which 29 (72.5%) received hematopoietic stem cell transplant (HSCT)-related therapy. At BrC onset, the most administered class of antifungal agents were echinocandins, administered to 70% of patients. Candida guilliermondii complex was the most frequently isolated species (32.5%), followed by C. parapsilosis (30%). These two isolates were echinocandin-susceptible in vitro but had naturally occurring FKS gene polymorphisms that reduced echinocandin susceptibility. Frequent isolation of these echinocandin-reduced-susceptible strains in BrC may be associated with the widespread use of echinocandins. In this study, the 30-day crude mortality rate in the group receiving HSCT-related therapy was significantly higher than in the group not receiving it (55.2% versus 18.2%, P = .0297). Most patients affected by C. guilliermondii complex BrC (92.3%) received HSCT-related therapy and had a 30-day mortality rate of 53.8%; despite treatment administration, 3 of 13 patients had persistent candidemia. Based on our results, C. guilliermondii complex BrC is a potentially fatal condition in patients receiving HSCT-related therapy with echinocandin administration., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: To meet the increasing demand for home healthcare in Japan, as part of the national healthcare system, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012 respectively. This study aimed to evaluate whether HCSCs has succeeded in providing 24-h home care services through the end of life., Methods: A retrospective cohort study was conducted using the national database in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and September 2015, and used general clinics, conventional HCSCs, or enhanced HCSCs. Each patient was followed up for 6 months after the first visit. The outcome measures were (i) emergency house call(s), (ii) hospitalization(s), and (iii) end-of-life care defined as in-home death. Multivariable logistic regression analyses were performed for statistical analysis., Results: The analysis included 160,674 patients, including 13,477, 64,616, and 82,581 patients receiving regular home visits by general clinics, conventional HCSCs, and enhanced HCSCs respectively. Compared to general clinics, the use of conventional and enhanced HCSCs was associated with an increased likelihood of emergency house calls (adjusted odds ratio [aOR] and 95% confidence intervals [CIs] of 1.62 [1.56-1.69] and 1.86 [1.79-1.93], respectively) and a decreased likelihood of hospitalizations (aOR [95% CIs] of 0.86 [0.82-0.90] and 0.88 [0.84-0.92] respectively). Among 39,082 patients who died during the follow-up period, conventional and enhanced HCSCs had more in-home deaths (aOR [95% CIs] of 1.46 [1.33-1.59] and 1.60 [1.46-1.74], respectively) compared to general clinics., Conclusions: HCSCs (especially enhanced HCSCs) provided more emergency house calls, reduced hospitalization, and enabled expected deaths at home, suggesting that further promotion of HCSCs (especially enhanced HSCSs) would be advantageous., (© 2023 The American Geriatrics Society.)

Background: Japan has conducted a nationwide annual health check-up program since 2008, focusing on metabolic syndrome and subsequent health guidance in individuals at high risk for cardiovascular disease. However, the adherence rate to health guidance invitations was assumed to be low in previous reports. Therefore, this study aimed to characterize adherence patterns in the program and identify major predictors of adherence to health guidance invitations., Methods: We studied 186,316 adults (aged 40-74 years) who were included in a nationwide employer-sponsored insurer's database in Japan at the beginning of the fiscal year 2017. We first described adherence to health check-ups, the proportion of individuals with high cardiovascular risk, and adherence to health guidance invitations. Predictors of adherence to the invitation were then identified among eligible high-risk individuals., Results: In 2017, 71.7% of the study population (n = 133,573) underwent health check-ups, among whom 23.2% (n = 30,979) were invited for health guidance because of their high cardiovascular risk. Among those individuals, 35.2% (n = 10,614) received health guidance. Predictors of improved adherence to health guidance invitation were older age, more concerning blood pressure or laboratory data results, and self-reported motivation for a lifestyle change., Conclusion: Though 70% of eligible adults attended Japan's annual cardiovascular risk check-ups, only 35% of individuals with high cardiovascular risk adhered to health guidance invitations. Future policy reforms to improve adherence to this program should target younger individuals and those with mild stages of hypertension, diabetes, or dyslipidemia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The adverse effects of hard contact lenses (HCL) on the corneal endothelium have been studied in the short term; however, long-term effects remain still unclear. In this study, we analyzed the effect of long-term HCL use on corneal endothelial cell density (ECD) and morphology in healthy Japanese individuals. This cross-sectional observational study included individuals using HCL for refractive errors examined at a single specialty eye hospital. Patient age, duration of HCL usage, ECD, coefficient of variation of the cell area (CV), and rate of appearance of hexagonal cells (6A) obtained via non-contact specular microscopy were assessed. We analyzed 8604 eyes (mean age: 35.6 ± 10.0 years, 837 males, 3465 females). The mean duration of HCL usage was 14.7 ± 9.1 (range, 1-50) years. Multivariate analysis revealed that ECD significantly correlated with age (P < 0.001) but not with duration of usage; however, CV and 6A significantly correlated with both factors (P < 0.001). Univariate analysis revealed that CV and 6A correlated with duration of usage (all, P < 0.001). According to our results, CV and 6A correlated with the duration of HCL usage in ophthalmologically healthy Japanese individuals. Therefore, it is important to monitor corneal endothelial morphology in long-term HCL wearers., (© 2023. The Author(s).)

Purpose: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD)., Design: Prospective observational cohort study., Participants: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society., Methods: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant., Main Outcome Measures: The best-corrected visual acuity (BCVA) 6 months after surgery., Results: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10 -7 ; -0.076, P = 1.6 × 10 -3 , respectively). On the other hand, there were no statistically significant differences for the other comparisons., Conclusions: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

HCT recipients reportedly have a high mortality rate after developing COVID-19. SARS-CoV-2 vaccination is generally useful to prevent COVID-19. However, its safety and efficacy among HCT recipients remain elusive. This large-scale prospective observational study including 543 HCT recipients with 37-months interval from transplant demonstrated high safety profiles of mRNA vaccine: only 0.9% of patients avoided the second dose due to adverse event or GVHD aggravation following the first dose. Regarding the efficacy, serological response with a clinically relevant titer (≥250 BAU/mL) was obtained in 397 (73.1%) patients. We classified the remaining 146 patients as impaired responders and compared the clinical and immunological parameters between two groups. In allogeneic HCT recipients, multivariable analysis revealed the risk factors for impaired serological response as follows: age (≥60, 1 points), HLA-mismatched donor (1 points), use of systemic steroids (1 points), absolute lymphocyte counts (<1000/μL, 1 points), absolute B-cell counts (<100/μL, 1 points), and serum IgG level (<500 mg/dL, 2 points). Notably, the incidence of impaired serological response increased along with the risk scores: patients with 0, 1-3, and 4-7 points were 3.9%, 21.8%, and 74.6%, respectively. In autologous HCT recipients, a shorter interval from transplant to vaccination was the only risk factor for impaired serological response. Our findings indicate that two doses of SARS-CoV-2 vaccine are safe but insufficient for a part of HCT recipients with higher risk scores. To improve this situation, we should consider additional treatment options, including booster vaccination and prophylactic neutralizing antibodies during the SARS-CoV-2 pandemic., (© 2022 Wiley Periodicals LLC.)

To evaluate the clinical efficacy of a new enzyme-linked immunosorbent assay (ELISA) system for simultaneously detecting three islet cell autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) (3 Screen ICA ELISA) in Japanese patients with acute-onset type 1 diabetes (T1D). In addition, clinical factors affecting the 3 Screen ICA ELISA index were investigated. We compared the positivity values of 3 Screen ICA ELISA with that of each autoantibody alone in 97 patients with acute-onset T1D (mean age 48.7 years, 49% male) and 100 non-diabetic subjects (mean age 47.0 years, 50% male). Serum thyroid stimulating hormone receptor antibody, thyroid peroxidase antibody (TPOAb) and thyroglobulin autoantibody levels were also evaluated. The cut-off value of the 3 Screen ICA ELISA was determined based on the 97 th percentile of 100 non-diabetic controls (threshold for positivity, ≥14 index). The mean age of disease onset and duration of diabetes were 34.2 years and 14.5 years, respectively. Among all T1D patients, the positivity of 3 Screen ICA ELISA was 71.1%, while that of GADA, IA-2A, and ZnT8A were 59.8%, 25.8%, and 25.8%, respectively. The median 3 Screen ICA index was 121.9 (8.7-468.2) and was associated with titers of each autoantibody, most so with GADA, and was significantly higher in TPOAb-positive patients than in TPOAb-negative patients. Our findings suggests that the 3 Screen ICA ELISA may be a time-saving diagnostic tool for evaluating islet autoantibodies in acute-onset T1D patients.

Background: Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer., Methods: In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment)., Results: Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths., Conclusions: In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs., Gov Identifier: NCT03343054., (© 2022. The Author(s).)

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Second or subsequent allogeneic HCT using unrelated cord blood has been performed for adult patients with AML who have relapsed after a previous allogeneic HCT. Although outcomes after unrelated cord blood transplantation (CBT) as the first allogeneic HCT have significantly improved in recent years, it is unclear whether survival and engraftment improve after CBT as the second or subsequent allogeneic HCT for adult AML patients relapsing after a previous allogeneic HCT. The objective of this retrospective study was to evaluate trends of survival and other transplantation outcomes after single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT over the past 19 years in Japan. We retrospectively assessed survival trends and other outcomes of single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT according to the time period of CBT (2001-2007, 2008-2013, or 2014-2019) using a nationwide Japanese database. The median age was 45 years among 1109 CBTs, and 844 (78.6%) patients were not in complete remission at the time of CBT. Over the 3 time periods, there was a progressive increase in higher cryopreserved cord blood total nucleated cell dose and myeloablative conditioning regimens. The 2-year overall survival was 14.0% in 2001-2007, 19.9% in 2008-2013, and 24.4% in 2014-2019 (P <.001 by log-rank trend test). The 2-year relapse-related mortality was 54.0% in 2001-2007, 44.4% in 2008-2013, and 39.1% in 2014-2019 (P < 0.001 by Gray's test), but nonrelapse mortality was not significantly different across the time periods (P = 0.557 by Gray's test). The 42-day neutrophil engraftment also significantly improved (62.9% in 2001-2007, 69.7% in 2008-2013, and 79.9% in 2014-2019; P < 0.001 by Gray's test). Our data demonstrate significant improvements in overall and relapse-related mortality, as well as neutrophil engraftment, after single-unit unrelated CBT as a second or subsequent allogeneic HCT for adult patients with AML relapsed after previous allogeneic HCT over the past 19 years., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, donor grafts are frequently cryopreserved to ensure that a graft is available before starting a conditioning regimen. However, there have been conflicting reports on the effect of cryopreservation on transplantation outcomes. Also, the impact of cryopreservation may differ in bone marrow (BM) transplantation (BMT) and peripheral blood stem cell (PBSC) transplantation (PBSCT). In this retrospective study, we analyzed the clinical data of both cryopreserved unrelated BMTs (n = 235) and PBSCTs (n = 118) and compared these with data from a large control cohort without cryopreservation including 4133 BMTs and 720 PBSCTs. Among the patients with cryopreserved grafts, 10 BMT recipients (4.3%) and 3 PBSCT recipients (2.5%) did not achieve neutrophil engraftment after transplantation, including 4 of the former and all 3 of the latter who died early before engraftment. In a multivariate analysis, cryopreservation was not associated with neutrophil engraftment in BMT but significantly delayed neutrophil engraftment in PBSCT (hazard ratio [HR], .82; 95% confidence interval [CI], .69 to .97; P = .023). There was an interaction with borderline significance between cryopreservation and the stem cell source (P = .067). Platelet engraftment was delayed by cryopreservation after both BMT and PBSCT. Only 2 cryopreserved grafts (<1%) were unused during the study period. The cryopreservation of unrelated donor BM and PBSC grafts is associated with a slight delay in neutrophil and platelet engraftment but an acceptable rate of graft failure. PBSC grafts may be more sensitive to cryopreservation than BM grafts. Cryopreservation is a reasonable option during COVID-19 pandemic, provided that the apheresis and transplantation centers are adept at cryopreservation. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., Competing Interests: Conflict of interest statement There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: The frequency, mortality, and morbidity of very low birth weight (VLBW) infants with congenital heart disease (CHD) in Asian countries are limited. In addition, little is known about the risk factors of death in these infants., Methods: A retrospective, multicenter cohort study was conducted. VLBW infants with CHD born between 2006 and 2010, and followed to 5 years of age, were included in the analysis. Multiple logistic regression analysis was performed to identify the risk factors of death., Results: Among 3247 VLBW infants, 126 various CHDs (3.9 %) were identified. The most common lesions were ventricular septal defect, tetralogy of Fallot (TOF), and coarctation of the aorta/interrupted aortic arch, in that order. The proportions of left-sided and right-sided outflow obstruction (TOF, pulmonary stenosis) were 15.1 % and 15.9 %, respectively. Trisomy 18 and trisomy 13 were present in 32 (25.4 %) of 126 VLBW infants with CHD. Nine patients were lost to follow-up. Overall, 45 patients (35.7 %) died up to 5 years of age. Serious CHD [odds ratio (OR), 19.2; 95 % confidential interval (CI), 3.94-93.11; p < 0.0001], sepsis (OR, 42.3; 95 % CI, 5.39-332.22; p < 0.0001), chromosomal /named anomalies (OR, 7.50; 95%CI, 2.09-26.94; p = 0.001), and no-invasive treatments (OR, 9.89; 95%CI, 2.28-42.91; p = 0.001) were associated with death. On excluding chromosomal anomalies, twelve of 71 patients (16.9 %) died, and only sepsis (OR, 35.5, 95%CI, 2.63-477.1; p = 0.0008) was an independent risk factor., Conclusions: Trisomy 18 and trisomy 13 of chromosomal anomalies are frequently associated with VLBW infants with CHD. The mortality of VLBW infants with CHD is high, even when chromosomal anomalies are excluded. Sepsis has a significant impact on death in VLBW infants with CHD., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

ABCC10/MRP7, an ATP-binding cassette (ABC) transporter, has been implicated in the extracellular transport of taxanes. Our group reported that the ABCC10 single nucleotide polymorphism (SNPs), rs2125739, influences docetaxel cytotoxicity in lung cancer cell lines as well as its side effects in clinical practice. In this study, we investigated whether the rs2125739 variant could affect paclitaxel (PTX) cytotoxicity in lung cancer cell lines. We also investigated the effect of rs2125739 on the efficacy and safety of nanoparticle albumin-bound PTX (nab-PTX) in clinical practice. The association between rs2125739 genotypes and the 50% inhibitory concentration (IC 50 ) of PTX was investigated in 18 non-small cell lung cancer (NSCLC) cell lines, HeLa cells, and genome-edited HeLa cells. Next, blood samples from 77 patients with NSCLC treated with carboplatin plus nab-PTX were collected and analyzed for six SNPs, including rs2125739. The clinical outcomes among the different genotype groups were evaluated. In NSCLC cell lines, HeLa cells, and genome-edited HeLa cells, the IC 50 was significantly higher in the ABCC10 rs2125739 T/T group than in the T/C and C/C groups. In 77 patients with NSCLC, there were no significant differences in clinical outcomes between the T/T and T/C groups. However, the rs2125739 T/T genotype was associated with a higher frequency of Grades 3/4 neutropenia. In contrast, there was no association between other SNPs and clinical efficacy or neutropenia. Our results indicate that the ABCC10 rs2125739 variant is associated with neutropenia in response to nab-PTX treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study assessed the epidemiological characteristics of 45 congenital rubella syndrome cases in Japan following the 2012-2013 rubella epidemic. Rubella still poses significant health burdens and the uptake of rubella-containing vaccines among women of childbearing age should be improved., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Isavuconazonium sulfate is the water-soluble prodrug of the novel, broad-spectrum, triazole antifungal agent isavuconazole. A size 0 elongated hard capsule containing 100 mg equivalent of isavuconazole is the currently marketed oral formulation in countries where it is approved. An alternative oral formulation, based on a lower-strength and smaller-size capsule, is required for pediatric and adolescent patients, as well as for some adult Japanese patients, especially those with difficulties swallowing larger capsules. This study was conducted to evaluate the bioequivalence of a size 0 elongated capsule containing 100 mg equivalent of isavuconazole and a size 3 capsule containing 40 mg equivalent of isavuconazole, after administration of 200 mg equivalent of isavuconazole (5 size 3 capsules or 2 size 0 elongated capsules) under fasted conditions. Bioequivalence of isavuconazole between the formulations was demonstrated, since point estimates (90%CI) for the ratio of the size 0 elongated capsules vs the size 3 capsules for maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration were within the acceptable range of 0.8 to 1.25. It was confirmed that both formulations were well tolerated, and no new safety signals were observed in healthy Japanese adult male subjects., (© 2022 Asahi Kasei Pharma Corporation. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance. A randomized controlled trial with a 4-week consumption of barley or control food was conducted. We conducted an integrated analysis of the intestinal microbiome and metabolome and analyzed the relationship with improvement of glucose tolerance. (3) Results: We found that metabolites such as azelate were significantly increased after barley consumption. Furthermore, the subjects whose glucose tolerance was slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. (4) Conclusions: Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment.

Background: The impact of body mass index on incidence of herpes zoster is unclear. This study investigated whether body mass index was associated with a history of herpes zoster and incidence during a 3-year follow-up, using data from a prospective cohort study in Japan., Methods: In total, 12,311 individuals were included in the cross-sectional analysis at baseline, of whom 1,818 with a history of herpes zoster were excluded from the incidence analysis, leaving 10,493 individuals. Body mass index (kg/m 2 ) was classified into three categories (underweight: <18.5; normal: 18.5 to <25; and overweight: ≥25). To evaluate the risk of herpes zoster, we used a logistic regression model for prevalence and a Cox proportional hazard regression model for incidence., Results: Being overweight or underweight was not associated with herpes zoster prevalence at baseline. The multivariate hazard ratios of herpes zoster incidence for overweight versus normal-weight groups were 0.67 (95% confidence interval, 0.51-0.90) in all participants, and 0.57 (95% confidence interval, 0.39-0.83) in women, with no significant difference for men., Conclusion: Being overweight was associated with a lower incidence of herpes zoster than being normal weight in older Japanese women.

Purpose: There have been very few reports of secondary malignancies after breast cancer treatment in Asia, particularly in Japan. This study aimed to evaluate the risk of secondary malignancies after radiotherapy (RT) in Japanese breast cancer patients., Methods: This single-center retrospective study included patients who underwent RT between July 1961 and September 2006 for postoperative breast cancer. A total of 702 patients with a follow-up period of more than 5 years were analyzed. All malignancies observed at more than 5 years after the start of RT were defined as secondary malignancies. To calculate the relative risk (RR) of secondary malignancies, we applied data from the National Cancer Center in Japan., Results: The median observation period was 9.7 (interquartile range 7.1-18.2) years. The cumulative person-years of observation were 6879.4. The RR of contralateral breast cancer increased by 1.85-fold (95% confidence interval [CI] 1.05-3.26) among patients compared with that among the general population; however, the difference was not significant (p = 0.053). The RR of secondary malignancies other than breast cancer increased by 2.71-fold (95% CI 1.99-3.70, p < 0.001) among the patients compared with the general population. Even when only malignancies detected more than 10 years after RT were defined as secondary malignancies, the RR of secondary malignancies other than breast cancer was 1.91 (95% CI 1.33-2.73, p < 0.001)., Conclusion: The incidence of secondary malignancies after RT may be somewhat higher in Japanese patients with breast cancer than in the general population., (© 2022. The Author(s).)

This study examined college students' perceptions of the association between smoking and novel coronavirus disease 2019 (COVID-19), changes in smoking behavior, and interest in quitting categorized by smoking device, to identify public health challenges. A questionnaire survey was conducted among 8,547 students in a Japanese university in March and April 2021. In response to "Awareness of the increased risk of COVID-19 infection due to smoking and the tendency to develop severe disease", current smokers (70.2%) were more aware of the risk than non-smokers (49.8%) (p < 0.001), with no significant difference according to smoking device (p = 0.213). "Interest in quitting smoking" (p = 0.323), and "Changes in smoking behavior during the COVID-19 pandemic" (p = 0.146) did not differ by smoking device. However, approximately 50% of the respondents answered that they were not interested in quitting smoking, while two-thirds reported that the number of cigarettes they smoked did not change during the pandemic. During the COVID-19 pandemic, college students were found to be less interested in quitting and not likely to change their smoking behavior, despite the knowledge of the increased risk of COVID-19 transmission and severity of disease from smoking, regardless of smoking device.