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Introduction: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity., Aim: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273)., Methods: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT)., Results: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed., Conclusion: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: The effect of polypharmacy on older patients with cancer is unclear. This study aimed to explore the effect of polypharmacy on the outcomes of treatment in older patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors., Materials and Methods: We retrospectively reviewed the records of older patients (aged ≥65 years) with advanced NSCLC who received PD-1/PD-L1 inhibitors with or without platinum-based chemotherapy as first-line treatment from March 2016 to December 2020. Patients with driver oncogenes or Eastern Cooperative Oncology Group performance status (PS) ≥2 were excluded. Polypharmacy was defined as receiving five or more oral or inhaled medications at baseline. We compared the progression-free survival (PFS), overall survival (OS), and mean cumulative length of hospital stays between the polypharmacy and non-polypharmacy groups., Results: A total of 122 patients, with a median age of 72 years (range, 65-89 years), were included in the analysis. Of the patients, 34 (27.8%) had a PS of 0 and 68 (55.7%) had a PD-L1 tumor proportion score (TPS) of ≥50%. The median number of oral or inhaled medications was 4 (range, 0-12), and 60 (49.1%) patients were taking ≥5 medications (polypharmacy). Age and Charlson Comorbidity Index score were significantly higher in the polypharmacy group (P = 0.01 and P < 0.001, respectively). Compared with the non-polypharmacy group, the polypharmacy group had a similar median PFS (6.7 vs. 8.5 months, P = 0.94) and a shorter median OS (17.3 vs. 26.0 months, P = 0.04). In the polypharmacy group, the adjusted hazard ratio for OS (adjusted for age, PS, and PD-L1 TPS) was 1.65 (95% confidence interval, 1.04-2.86, P = 0.03). Patients in the polypharmacy group had longer hospital stays (46.3 ± 7.5 vs. 27.7 ± 4.1 days/person, P < 0.05) and more emergency hospitalizations (1.6 ± 0.3 vs. 0.8 ± 0.1 times/person, P < 0.05) during the first year., Discussion: Polypharmacy was associated with shorter survival time and longer hospitalization in older patients with advanced NSCLC receiving first-line immunotherapy with or without chemotherapy., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships with other individuals or organizations that could inappropriately influence this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We devised a method that combines the 3D-Dixon-gradientecho (GRE) method with an improved motion-sensitized driven-equilibrium (iMSDE) to suppress blood flow signals., Purpose: The purpose of this study was to evaluate the effectiveness of the new method we developed plaque imaging method (3D-Dixon-GRE with the iMSDE method)., Study Type: Retrospective cohort., Population: Thirty-nine patients who underwent cervical plaque imaging., Field Strength/sequence: 3.0 T/3D-GRE., Assessment: Signal intensities of the common carotid artery, aorta, plaque, muscle, and subcutaneous fat were measured through the VISTA and the 3D-Dixon-GRE with iMSDE methods, and each contrast was calculated., Statistical Test: Used the Mann Whitney U test. P-values below 0.05 were considered statistically significant., Results: Plaque and muscle contrast estimated through the VISTA method and 3D-Dixon-GRE with iMSDE method was 1.60 ± 0.96 and 2.04 ± 1.06, respectively, (P < 0.05). The contrast between the flow (common carotid artery and Aorta) and muscle according to the VISTA method and 3D-Dixon-GRE with iMSDE method was 0.24 ± 0.11 and 0.40 ± 0.12, respectively (P < 0.001). Finally, the mean contrast for subcutaneous fat and muscle at six locations was 3.05 ± 1.25 and 0.81 ± 0.23 for the VISTA method and 3D-Dixon-GRE with the iMSDE method, respectively (P < 0.001)., Data Conclusion: Compared to the conventional method (VISTA), the 3D-Dixon-GRE with iMSDE method is preferable in relation to the fat suppression effect, but it is disadvantageous regarding blood flow signal suppression. Therefore, the 3D-Dixon-GRE with the iMSDE method could be considered useful for plaque imaging., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Aspiration pneumonia has a high recurrence rate, and oral care by dentists has been found effective in preventing its onset; however, this has not been evaluated using prospective studies. Therefore, we conducted a prospective study to evaluate the effectiveness of professional oral care by dentists in reducing aspiration pneumonia recurrence in older adult patients., Methods: In this prospective cohort study, we evaluated a dental oral care intervention, using a historical control group (control group). It was conducted at a single-centre regional core hospital in Japan that serves a large number of patients aged older than 80 years. Patients who were hospitalised for aspiration pneumonia were included in this study. During the study period (1 April 2021 to 31 March 2022), the clinical group received weekly professional cleaning by a dentist and the control group received standard oral care by a nurse as usual from 1 April 2020 to 31 March 2021. The dentist oral care group received weekly professional oral care from a dentist and was followed prospectively for 1 year. A Kaplan-Meier analysis was used to evaluate the timing of recurrent aspiration pneumonia or death. A Cox proportional hazards model was used to obtain a hazard ratio and determine the 95% confidence intervals., Results: There were 91 participants in the clinical group and 94 in the control group. The mean age of participants was 85 years, and 75 (40.5%) were female. The recurrence rate was 27.5% in the clinical group and 44.7% in the control group (P = .005). Professional cleaning by a dentist reduced the risk of recurrence of aspiration pneumonia by approximately 50% (adjusted hazard ratio, 0.465; 95% confidence interval, 0.278-0.78)., Conclusions: Professional cleaning by a dentist was associated with a lower rate of aspiration pneumonia recurrence than nurse-provided conventional oral care., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Factors that determine clinical responses to vonoprazan remain unknown. This study aimed to characterize plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Fifty-three patients who were receiving vonoprazan for at least 3 days were enrolled. Blood samples for determination of plasma vonoprazan and its metabolite (ODA-VP) were obtained. Plasma 4β-hydroxycholesterol (4β-OHC), CYP3A5 and ABCB1 genotypes, and plasma gastrin were determined. CYP3A recognition for vonoprazan was evaluated using recombinant CYP3A proteins. Plasma vonoprazan levels exhibited a large interindividual variation. The absolute plasma concentration of vonoprazan was correlated with its dose-normalized value, and had a positive correlation with the inverse value of its metabolic ratio. A negative correlation was observed between plasma vonoprazan and 4β-OHC levels. The metabolic ratio of vonoprazan was positively correlated with the plasma 4β-OHC level. Genetic variants of CYP3A5 and ABCB1 were not associated with the plasma concentration of vonoprazan and its metabolic ratio. Possible saturated metabolism of vonoprazan to its major metabolite was observed at a therapeutic dose. Although the CYP3A5 genotype did not alter plasma vonoprazan, CYP3A activity based on plasma 4β-OHC partially explained the variation in plasma vonoprazan in patients with digestive system disorders., (Copyright © 2024 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to clarify nursing students' self-assessed levels of nursing skills at a nursing university at graduation and discuss how education and clinical experiences for students and post-licensure nurses should be improved, especially focusing on oncology nursing., Methods: The study population comprised fourth-year students from 2017 to 2019 at the Faculty of Health Science and Nursing, Juntendo University, who had completed all stipulated clinical placements. The Japanese government determined 141 nursing skills and their target levels. Students subjectively evaluated their achieved levels for the 141 nursing skills after the final clinical placement., Results: Of the 141 nursing skills, 81 (57%) were rated as "skills with easy-to-achieve targets" and five were rated as "skills with difficult-to-achieve targets." All nursing skills in the two subcategories of environmental adjustment skills and comfort management skills were rated as "skills with easy-to-achieve targets." Nursing skills with low target achievement rates were for patients with oral intake difficulties, unstable respiratory status, and those requiring glycemic control. These skills are also important in oncology nursing., Conclusions: It cannot be concluded that the nursing university students fully achieved the target levels of nursing skills, as determined by the Japanese government. These findings may facilitate discussions on teaching nursing skills and their target levels at the time of graduation from nursing universities or post-employment., (© 2024 The Author(s).)

Introduction: Risk factors for severe COVID-19 associated with people living with HIV (PLWH) have not been well studied in Japan. In this study, we aim to reveal how having AIDS and comorbidities affect adverse COVID-19 outcomes., Methods: This observational, retrospective study examined the clinical outcomes for PLWH hospitalized as COVID-19 inpatients in Japan, using data extracted from hospitals with the Diagnosis Procedure Combination (DPC) system between January 2020 and December 2021. From 4672 records of HIV patients receiving antiretroviral therapy, 85 adult PLWH became hospitalized with COVID-19. The associations between patients' AIDS diagnosis, comorbidities, and their adverse COVID-19 outcomes (mild/moderate and severe/death) were analyzed., Results: Among 85 studied patients, 78 were male (91.8%) with mean (SD) age of 48 (14.4) years. 75 (88.2%) were found to be COVID-19 mild/moderate; 9 (10.6%) were severe; 1 (1.2%) died. Older age (p = 0.002) and hypertension (p = 0.032) were significantly associated with progressing to severe COVID-19 or death. AIDS and other AIDS-defining illnesses were not found to be significant risk factors in this study., Conclusions: While interpretation of the results from this hospital claim database study warrants caution, we found that among PLWH hospitalized as COVID-19 inpatients in Japan, those who are older or with hypertension have a higher risk for progression to severe COVID-19 outcomes, suggesting a careful monitoring of clinical course for these patients., Competing Interests: Declaration of competing interest None., (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: This study aimed to investigate the performance of oral assessment and health care education at nursing schools across Japan to identify problems and the need for oral health professional support., Methods: The participants were the academic staff in charge of oral health care education in the basic, adult, gerontological, and home nursing fields of 295 schools in Japan that offered a bachelor's degree in nursing. A questionnaire was sent to 1180 heads of the nursing fields of these schools. They were requested to have oral health care educators complete the survey; data on the performance of oral assessment and health care education and human resources allocated were collected through a questionnaire., Results: A total of 311 (26%) questionnaires were returned, 196 (63%) of which were completed by oral health care educators. Regarding the performance of oral assessment education, the majority (71%) of them spent less than 2 hours in teaching, and only 24.5% taught the usage of oral assessment tools. Regarding the performance of oral health care education, more than 90% spent less than 2 hours in lecture-based and practical oral health care education, respectively. Less than half taught the association of periodontal diseases with diabetes and cardiovascular diseases and use of fluoride for caries prevention in the lectures, and only approximately 30% taught the usage of an interspace brush or dental floss. Moreover, less than 10% of oral health professionals taught oral health care in lectures or practical oral health care., Conclusions: This study revealed problems associated with oral assessment and health care education in Japanese nursing schools. To address these, support from oral health care professionals is required. Further studies are also required to reveal problems in oral assessment and health care education in other nursing schools that do not offer a bachelor's degree programme in Japan and other countries., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction/background: The proper duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains unclear. Previously, sponsor-initiated clinical trials have more often used either a maximum 2-year fixed duration of ICI treatment or continuous treatment until documented disease progression. The study aimed to evaluate the association between ICI treatment duration (2-year fixed or continuous) and prognosis in patients with advanced NSCLC., Patients and Methods: The medical records of 425 patients with NSCLC who received ICI before August 31, 2019 were retrospectively reviewed., Results: No differences in time to treatment failure > 24 months (TTF-24) were detected between patients who underwent ICI treatment for > 2 years and patients who stopped ICI treatment at 2 years. Treatment-related adverse events tended to be higher in the patients with ICI treatment > 2 years., Conclusion: ICI treatment > 2 years did not significantly prolong the TTF compared with ICI treatment = 2 years, but it did increase the incidence of treatment-related adverse events., Competing Interests: Competing Interest Haruki Kobayashi reports personal fees from Eli Lilly, Novartis, Taiho Pharmaceutical, Chugai pharma, AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb Japan, outside the submitted work. Kazushige Wakuda reports grants from AstraZeneca, Chugai pharma, Novartis, Abbvie, AMGEN, Daiichi Sankyo, Dizal Pharma; personal fees from Chugai pharma, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono Pharmaceutical, Daiichi Sankyo, Jassen Pharmaceutial, Takeda, Nippon Kayaku, outside the submitted work. Tateaki Naito reports grants from Otsuka Pharmaceutical; personal fees from Ono Pharmaceutical, HELSINN SA, outside the submitted work. Nobuaki Mamesaya reports grants from Boehringer Ingelheim; personal fees from Chugai pharma, AstraZeneca, Boehringer Ingelheim, Taiho Pharmaceutical, MSD, Ono Pharmaceutical, outside the submitted work. Ryo Ko reports grants from MSD, AstraZeneca; personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Pfizer, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Takeda, MSD, outside the submitted work. Akira Ono reports personal fees from Chugai pharma, AstraZeneca, Ono Pharmaceutical, outside the submitted work. Hirotsugu Kenmotsu reports grants from Ono Pharmaceutical, Novartis, Eli Lilly, AstraZeneca, Loxo Oncology; personal fees from AMGEN, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai pharma, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, outside the submitted work. Haruyasu Murakami reports grants from AstraZeneca, Chugai pharma, Takeda, Abbvie, Daiichi Sankyo, IQvia; personal fees from AstraZeneca, Chugai pharma, Takeda, Abbvie, Daiichi Sankyo, MSD, Ono Pharmaceutical, Bristol-Myers Squibb Japan, Pfizer, Novartis, Eli Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, Eisai, Nippon Kayaku, outside the submitted work. Tetsuo Shimizu reports personal fees from Eli Lilly, Taiho Pharmaceutical, Chugai Pharma, AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb Japan, Takeda, outside the submitted work. Yasuhiro Gon reports personal fees from Chugai pharma, outside the submitted work. Toshiaki Takahashi reports grants from AstraZeneca, Chugai Pharma, Eli Lilly Japan, Ono Pharmaceutical, MSD, Pfizer, AMGEN, Boehringer Ingelheim, Merck Biopharma; personal fees from AstraZeneca, Chugai Pharma, Eli Lilly Japan, Ono Pharmaceutical, MSD, Pfizer, Boehringer Ingelheim, Roche Diagnostics, Takeda, Yakult, outside the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Particle packed columns used for liquid chromatography (LC) can suppress a column internal band broadening (hereinafter referred to as band broadening) by packing monodisperse particles homogenously. However, a quantitative evaluation for the effects of particle shape and packed state on band broadening needs to be more investigated. In this study, we fabricated a model of particle packed bed using microfluid LC columns that have pillar array structure prepared by microfabrication technology, evaluating how structural factors inside of a column affect its band broadening. At first, microfluid LC columns was prepared using Si-quartz glass (Si-Q column) for the optimization of LC measurement system. Through the evaluation, it showed 11.6 times higher pressure tolerance compared to that of PDMS-soda lime glass (PDMS-g column). Then, an optimized LC measurement system was constructed using a microfluidic LC column made of Si-Q column, and it was confirmed that the measurement error was small enough and the LC measurement could be performed with high repeatability. Additionally, the effect of a distribution of structural size on band broadening was evaluated. It was confirmed that wide distribution of the structural size provided large band broadening in actual measurements. Comparing two columns having different structural log-normal distributions of 0 and 0.22 showed approximately 1.8 times difference in both real LC measurement. Lastly, the relationship between packed state and band broadening was evaluated. As packed state, we employed void arrangement and structural arrangement in the columns. Different location arrangements of 50 and 100 µm pillar sizes afforded different band broadening. Well-homogenized array showed approximately two times worse band broadening compared to that of delocalized array. Based on these results, the developed packed bed of particles model was able to evaluate the relation between structural factors and band broadening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Although pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension, not all patients are eligible. While balloon pulmonary angioplasty is an alternative for such patients, its efficacy and safety may differ between patients with and without surgically accessible lesions., Methods: This study involved 344 patients treated with balloon pulmonary angioplasty who were ineligible for pulmonary endarterectomy. Based on the angiographical lesion location, patients were divided into the surgically accessible (Group 1) and inaccessible (Group 2) groups, and percent changes in hemodynamics and clinical parameters before and after balloon pulmonary angioplasty were investigated. We also conducted survival analyses using Kaplan-Meier analysis., Results: While no differences in baseline characteristics were identified between the groups, balloon pulmonary angioplasty significantly improved hemodynamics in both groups, without any difference regarding the incidence of complications. Meanwhile, the percent changes in the mean pulmonary arterial pressure, pulmonary vascular resistance, 6-min walk distance, right ventricular area index on echocardiography, and the achievement rate of World Health Organization functional class I after balloon pulmonary angioplasty were significantly lower in Group 1 than in Group 2. The cumulative survival rates at 1, 5, and 10 years after balloon pulmonary angioplasty were not significantly different between the two groups (Group 1: 92.5%, 86.1%, 84.3%; and Group 2: 96.5%, 92.9%, 90.1%, respectively)., Conclusions: The outcome of balloon pulmonary angioplasty in inoperable patients with surgically accessible proximal lesions was acceptable; however, further investigations are necessary to clarify the optimal treatment for such patients., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Long-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function., Methods: Thirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed., Results: The serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes., Conclusions: Plasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To report the role of prostaglandin-associated periorbitopathy (PAP) severity in the surgical effectiveness of trabeculectomy (LEC)., Design: Retrospective observational case series., Participants: A total of 139 consecutive eyes of 139 Japanese subjects (74 men, 65 women; mean age ± standard deviation, 65.7 ± 10.6 years) who underwent LEC were included. All had primary open-angle glaucoma (POAG), no history of conjunctival incisional surgery, completed all postoperative visits for 12 months, and information on the PAP severity using the Shimane University PAP Grading System (SU-PAP)., Methods: Data were collected from a medical chart review at 2 hospitals., Main Outcome Measures: Comparison of surgical success rates among groups stratified by SU-PAP grades 0 to 3 by survival curve analysis using the definitions of failure based on surgical intervention other than laser suture lysis (LSL), intraocular pressure (IOP) reduction below 20%, postoperative IOP exceeding 15 mmHg (definition A) or 12 mmHg (definition B), and a postoperative IOP below 6 mmHg., Results: Twelve months postoperatively, the success rates of grades 0, 1, 2, and 3 were 86%, 68%, 40%, and 0%, respectively, for definition A (P < 0.0001, log-rank test) and 86%, 61%, 36%, and 0%, respectively, for definition B (P < 0.0001). Interventions other than LSL (P < 0.0001, Cochran-Armitage trend test), IOP reduction less than 20% (P = 0.010), and IOP exceeding 15 mmHg (P = 0.016) or 12 mmHg (P < 0.0001) were associated with surgical failure; IOP under 6 mmHg was not (P = 0.31). The proportional hazard model for definition A showed that compared with grade 0, grade 2 (risk ratio [RR], 5.82, P = 0.0043) and grade 3 (RR, 12.2, P = 0.0003) were associated with surgical failure. For definition B, grade 1 (RR, 3.53, P = 0.040), grade 2 (RR, 6.65, P = 0.0021), and grade 3 (RR, 12.0, P = 0.0003) were associated with surgical failure. Differences in age, gender, preoperative IOP and medications, refractive error, and simultaneous cataract surgery were not associated with surgical failure in both models., Conclusions: The preoperative presence of severe PAP worsens the 1-year success rate of LEC in patients with POAG. To retain the surgical effectiveness, treating physicians should prevent patients from progressing to severe PAP, an avoidable side effect, by switching or stopping the causative medications., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Plasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity., Methods: Infectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight., Results: The serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin., Conclusion: The glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflict of interest., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic and people's subsequent behavioral changes have decreased the cases of respiratory infection worldwide. However, research on infectious diseases with other transmission modes is insufficient. The aim was to assess the impact of the COVID-19 pandemic on non-respiratory infectious diseases: infectious enterocolitis, sexually transmitted diseases such as human immunodeficiency virus (HIV) infection and syphilis, and tick-borne diseases., Methods: This retrospective, cohort study used comprehensive surveillance data from the National Institute of Infectious Diseases in Japan from January 1, 2018, to December 31, 2021. The number of cases of infectious diseases before the COVID-19 pandemic (2018-2019) was compared with that during the COVID-19 pandemic (2020-2021). Reduction rates were calculated as the number of disease cases during the COVID-19 pandemic in 2020 and 2021, respectively, divided by the mean number of disease cases in 2018 and 2019., Results: The total numbers of cases of infectious enterocolitis, sexually transmitted diseases, and tick-borne diseases during the study period were 2,507,304 cases, 24,972 cases, and 3012 cases, respectively. The number of cases decreased for infectious enterocolitis and sexually transmitted diseases during the COVID-19 pandemic compared with before the COVID-19 pandemic, with an approximately 40-50% decrease in enterocolitis and 30-55% decreases in sexually transmitted diseases. However, cases of tick-borne diseases changed little, with a 0.2% increase in 2020 and a 6% increase in 2021., Conclusion: The COVID-19 pandemic had a different impact on the number of cases of infectious diseases depending on their mode of transmission., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The incidence of infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria has increased. This study aimed to clarify the risk factors and treatment strategies for febrile urinary tract infection (fUTI) caused by ESBL-producing bacteria in Japanese children., Methods: A retrospective observational study was conducted in 21 hospitals among children aged <16 years diagnosed with an fUTI between 2008 and 2017. Clinical data of children with fUTI caused by ESBL-producing and non-ESBL-producing bacteria were compared., Results: Of the 2049 cases of fUTI, 147 (7.2%) were caused by ESBL-producing bacteria. Children in the ESBL group were more likely to have a history of recent antibiotic use or prophylactic antibiotic use, and experience recurrent UTIs (P <0.001) compared with those in the non-ESBL group. Of the 124 cases of fUTI due to ESBL-producing bacteria that were reviewed, 20 and 100 had concordant and discordant antibiotic use, respectively, and four had unknown antibiotic susceptibility. The median time from the start of treatment to fever resolution was 24 hours and did not differ significantly by therapy group (P = 0.39)., Conclusion: ESBL-producing bacteria should be considered in children with recurrent UTIs and recent antibiotic use. Most children with fUTI experience clinical improvement regardless of the choice of antibiotic., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Two spirometry criteria have been proposed for early chronic obstructive pulmonary disease (COPD) in young smokers: 1) forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) < the lower limit of normal (LLN), and 2) FEV 1 decline ≥60 ml/year. These criteria have yet to be validated. This study explored clinical factors associated with these two spirometry criteria., Methods: This retrospective study analysed medical check-up data from 13,010 consecutive subjects aged <50 years who underwent current and 3 previous spirometry tests in Japan. Current ≥10 pack-year smokers were the main focus of analysis; those meeting one or more spirometry criteria were diagnosed with early COPD. Early COPD was categorized into three subtypes: FEV 1 /FVC < LLN and FEV 1 decline <60 ml/year (type 1), FEV 1 /FVC ≥ LLN and FEV 1 decline ≥60 ml/year (type 2), and FEV 1 /FVC < LLN and FEV 1 decline ≥60 ml/year (type 3)., Results: Of the 1579 current ≥ 10 pack-year smokers, 488 (30.9%) met the early COPD criteria. Multivariate multinomial logistic models adjusted for age, sex, height, body mass index (BMI) and smoking history indicated that past BMI increase and low exercise were associated with higher type 2 early COPD incidence (odds ratio (OR) [95% confidence interval (CI)] = 4.30 [3.10, 6.04], and 0.80 [0.69, 0.93], respectively) but not with higher type 1 incidence. A history of asthma was associated with higher type 3 incidence (OR [95% CI] = 1.98 [1.18, 3.07])., Conclusions: The 3 types of spirometry-based early COPD have different clinical factors. Their trajectories should be explored in longitudinal studies., Competing Interests: Declarations of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH)., Methods: This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated., Results: There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010-2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018)., Conclusions: The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Medication persistence has rarely been studied for integrase strand transfer inhibitor (INSTI)-based regimens among patients living HIV (PLWH) in Asia. This study investigated medication persistence for newly prescribed INSTI-based regimens in Japan by comparing single-tablet regimens (STRs) versus multiple-tablet regimens (MTRs), based on the Medical Data Vision database., Methods: Adult PLWH with ≥2 claims for antiretroviral therapy (ART) of interest between 1 January 2017 and 30 June 2018 were included if they had a ≥3-month continuous enrolment prior to the index date and a ≥6-month follow-up after the index date. Medication persistence was measured as the duration from initiation to discontinuation of the prescribed INSTI-based regimen., Results: Overall, 487 patients were included, with 220 in the STR cohort and 267 in the MTR cohort. Persistence was longer in the STR cohort than in the MTR cohort (mean days on the index regimens: 384.2 vs. 317.3, P < 0.001). MTRs were associated with a higher risk of discontinuation than STRs (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.18-2.52; P = 0.005). Other factors that were associated with discontinuation were backbone (emtricitabine/tenofovir disoproxil fumarate vs. emtricitabine/tenofovir alafenamide: HR, 5.64; 95% CI, 3.68-8.66; P < 0.001), third agent (raltegravir vs. elvitegravir/cobicistat: HR, 2.06; 95% CI, 1.10-3.86; P = 0.024), age (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and the number of non-ART index medications (HR, 1.16; 95% CI, 1.12-1.21; P < 0.001)., Conclusions: Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs., Competing Interests: Declaration of competing interest X. W. was an employee of Gilead Sciences. L. S. is an employee of StatinMED Research. T. N. has received consulting fees from Gilead Sciences., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2-7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10-17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic has shaped the dynamics of many diseases. This study aims to assess how the pandemic affected community-acquired pneumonia admission of all age groups among Japanese hospitals with various size and availability of COVID-19 wards. Our findings revealed a 44%-53% reduction in community-acquired pneumonia admission among 82 hospitals in Japan, from April through September of 2020, compared to the same period of 2019. Decreases were consistently found among hospitals with and without COVID-19 wards. The most significant decrease was found in the age group <20 years old. COVID-19 preventive measures and personal hygiene are considered to be effective measures to prevent the spreading of this disease. As vaccination progresses and the public gradually become less attentive to infection countermeasures, incidence of community-acquired pneumonia may increase in the coming season. Continued monitoring is required., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: With the expanded use of immunotherapy in medical oncology, effective patient education regarding immune-related adverse events (irAEs) is crucial for oncology nursing. Therefore, this study aimed to identify educational needs for preventing unscheduled hospitalizations due to severe irAEs., Methods: We retrospectively reviewed the medical records of 159 consecutive patients with lung cancer who received programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in 2020. We evaluated the frequency, severity, and unscheduled hospitalization due to irAEs based on the PD-1/PD-L1 inhibitor use. Educational needs were assessed based on initial symptoms, reporters, telephone consultation, and the time lag between symptom onset and hospital visit., Results: Among 159 patients evaluable for irAEs, 73 (45.9%) experienced 91 irAEs during the study period. Seventeen patients (10.7%) required unscheduled hospitalization due to severe irAEs after a median duration of 4.1 days from symptom onset, and 52.9% visited hospitals after telephone consultations from caregivers. Pneumonitis (10 events) was the most frequent irAE requiring hospitalization, followed by adrenal insufficiency (three events). The type and severity of irAEs varied based on PD-1/PD-L1 inhibitor use., Conclusions: The frequency of severe irAEs requiring hospitalization was high in patients who received PD-1/PD-L1 inhibitors for advanced lung cancer. The early detection of severe irAEs may be possible through education focusing on common irAEs that are potentially severe. Patients and caregivers should be aware of the importance of reporting slight changes in symptoms after PD-1/PD-L1 therapy initiation in a timely manner. Healthcare professionals need to acknowledge common irAEs and be qualified to implement systematic telephone triage of irAEs., (© 2022 The Authors.)

Objective: This study aimed to investigate nurses' perceptions of oral health care provision to inpatients in Japanese hospitals and the infection control measures taken by them after the coronavirus disease 2019 (COVID-19) lockdown to promote collaborative oral health care., Method: The participants were 1037 nurses working in inpatient wards at 4 hospitals in Fukuoka Prefecture, Japan. Data were collected through a questionnaire survey approximately 6 months after the first COVID-19 lockdown., Results: More than 90% of the 734 nurses participating in this study positively perceived the preventive effect of oral health care on aspiration pneumonia, ventilator-associated pneumonia, and viral infection. However, approximately half of them had negative perceptions about their knowledge and confidence regarding the control of COVID-19 with oral health care provision, and 84.7% expected to be provided with the necessary information by oral health professionals. Further, 537 nurses (73.2%) provided oral health care to their patients; 9 nurses (1.7%) responded that those patients who received oral health care decreased after the lockdown; and 12 (2.4%) responded that they could no longer collaborate with oral health professionals because of the lockdown. Additionally, 41.7% of them used neither protective glasses nor face shields even after the lockdown began., Conclusions: This study showed that almost all the nurses perceived the benefcial effect of oral health care for the prevention of viral infection and pneumonia. However, some nurses perceived that their oral health care provision and collaborative oral health care were negatively affected. It also showed that most nurses' knowledge, confidence, and use of infection control measures were insufficient. The results indicate that oral health professionals should support nurses in providing oral health care by providing them with information on COVID-19 infection control measures to prevent infection transmission., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients' HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00-34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53-20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21-9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43-8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80-6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This scoping review aims to identify the barriers in practice and clinical trials for oncology nurses in cancer cachexia. We used the framework proposed by Arksey and O'Malley and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Studies written in English and published between 2008 and 2021 were retrieved from five databases: MEDLINE, Cochrane Library, CINAHL, PsycINFO, and EMBASE. A total of 1075 studies were identified, and 34 full-text studies were assessed for eligibility by three researchers. Seventeen studies met the inclusion criteria. This review revealed several barriers to nursing practice and clinical trials in cancer cachexia. First, health-care professionals, including nurses, faced individual barriers (insufficient understanding and skills for diagnosis and management) and environmental barriers (lack of standardized screening tools or treatment options, difficulties in collaboration with other professions, and limited human resources) in practice. Second, studies on nurse-led interventions for cancer cachexia were relatively few and different in objectives, making it challenging to integrate the outcomes. Finally, there were no established educational programs for nurses that explicitly focused on cancer cachexia. This scoping review revealed individual and environmental barriers in nursing practice. In addition, there have relatively few clinical trials involving oncology nurses in cancer cachexia. Continuing education for nurses should cover cancer cachexia to improve the quality of oncology care in the future. It is also necessary to standardize practical assessment tools that are easy to assess daily and lead to interventions and develop nurse-led multidisciplinary care., Competing Interests: The corresponding author, Prof. Tateaki Naito, is the associate editor of the journal., (Copyright: © 2021 Ann & Joshua Medical Publishing Co. Ltd.)

Cholesterol, an essential lipid for cell signaling and structural integrity of cellular membranes, is highly enriched in the plasma membrane (PM). However, the regulatory mechanisms that control its biosynthesis and uptake both reside in the endoplasmic reticulum (ER). Thus, the ER needs to constantly monitor the levels of PM cholesterol. This is in part mediated by regulated transport of a biochemically defined pool of cholesterol, termed "accessible" cholesterol, from the PM to the ER via evolutionarily conserved ER-anchored lipid transfer proteins, the GRAMD1s/Asters (GRAMD1a/1b/1c) (Lam/Ltc proteins in yeast). GRAMD1s possess cytosolically exposed GRAM domain and StART-like domain followed by a transmembrane ER anchor. They form homo- and hetero-meric complexes and move to the contacts formed between the ER and the PM by sensing a transient expansion of the accessible pool of cholesterol in the PM via the GRAM domain and facilitate its extraction and transport to the ER via the StART-like domain. The GRAMD1b GRAM domain possesses distinct, but synergistic sites, for recognizing accessible cholesterol and anionic lipids, including phosphatidylserine, within the PM. This property of the GRAM domain contributes to regulated tethering of the PM to ER membrane where GRAMD1s are anchored and fine-tunes StART-like domain-dependent accessible cholesterol transport. Thus, cells use GRAMD1s to sense the levels of cholesterol in the PM and regulate transport of accessible PM cholesterol to the ER in order to maintain cholesterol homeostasis., (Copyright © 2021 Elsevier B.V. All rights reserved.)