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Background: Dialysis patients have a higher COVID-19 fatality rate than the general population and are priority candidates for SARS-CoV-2 vaccination. However, dialysis patients are immunocompromised, suggesting that they may develop a less immune response to COVID-19 vaccination than healthy individuals. Objective and Methods: A total of 358 hemodialysis patients who were twicevaccinated with BNT162b2 were included. SARS-CoV-2 IgG antibody titer was measured within 7 days to 1 month, 1∼2 months, and 3∼4 months after the second vaccination, and factors influencing antibody titer were statistically investigated. SARS-CoV-2 IgG measurement was performed using SARS-CoV-2 IgG II Quant Reagent (Abbott), which is a reagent to quantitatively measure IgG antibodies against the receptor-binding domain of SARS-CoV-2 spike protein. Results: The patients were 240 males (67%) and 118 females, ranging from 37 to 95 years old, with a median age of 70 years. Causes of kidney failure were diabetes mellitus in 35.2%, hypertensive kidney disease in 7.3%, glomerular disease in 30.5%, and polycystic kidney disease in 4.5% of the patients. Comorbidities were hypertension in 64.3% and diabetes in 48.9%. Steroids or immunosuppressive drugs were used in 9% of the patients. SARS-CoV-2 IgG antibody titers at 7 days to 1 month, 1 to 2 months, and 3 to 4 months (median 10, 42, and 98 days) after the second vaccination have the median of 4092 AU/mL(with interquartile range: 1354, 7592), 2199 (927, 4692), and 789 (323, 1559), respectively. Post-vaccination SARS-CoV-2 IgG titers were significantly correlated with Kt/V, the presence of autoimmune diseases, the use of steroids or immunosuppressive drugs, malignancy treatment, and serum albumin and hemoglobin levels. Multivariate analysis showed that the factors that decreased post-vaccination SARS-CoV-2 IgG titer were the use of steroids and immunosuppressive drugs, the presence of malignant tumors under treatment, and hypoalbuminemia. Conclusion: Compared to healthy subjects in previous reports, dialysis patients had lower SARS-CoV-2 IgG titers after COVID-19 vaccination, suggesting that the vaccine may not be sufficiently effective. In addition, SARS-CoV-2 IgG titers are likely to be even lower in patients at high risk for decreased immune response due to medications or comorbidities. Additional vaccination may be essential for hemodialysis patients who are expected to have low SARS-CoV-2 IgG titers.
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Objective: Self-restraint from activities due to the COVID-19 pandemic has limited the range of activities and interpersonal relationships for older persons. Moreover, prolonged restraint has been reported to increase the risk of frailty and sarcopenia. Therefore, we examined the effects of changes in exercise habits on physical function and psychological status of older patients with hypertension throughout their self-restraint lifestyle from 2020 to 2022 in the 1-year follow-up study. Design and Methods: Participants were patients with hypertension aged 65 years or older attending outpatient clinics at our institution who could obtain information on exercise habits, history of falls, comprehensive geriatric assessment, and muscle strength. We conducted the same survey in the first year and one year later. The subjects were classified into four groups by combining their exercise habits in the first year with or without one year later. That is Group A: with exercise habits at both times of the survey;Group B: with exercise habits in the first year and without exercise habits one year later;Group C: without exercise habits in the first year and with exercise habits one year later;and Group D: without exercise habits at both times of the survey. Written consent forms were obtained from all participants. Our institutional review board approved the study protocol. Results: The study participants were 183 patients (Group A: 119, Group B: 26, Group C: 17, Group D: 21). The age of the participants was 76.1 ± 5.5 years, 82 (44.8%) were male, and the duration of hypertension was 18.4 ± 11.5 years. Changes in exercise habits were not associated with physical function, history of falls, and comprehensive geriatric assessment at one year. However, when the results were examined separately for men and women, the geriatric depression scale was significantly higher in women in Group B (Dunnett test, p = 0.0094) than in Group A, suggesting that the tendency toward depression had progressed. Group B women also had more falls one year later (chi-square 12.04, p = 0.0072). Conclusions: In a 1-year follow-up study during the COVID-19 pandemic, a relatively high proportion of older patients with hypertension attending our hospital maintained their exercise habits, but 14% of cases lost their exercise habits. Only women showed the development of depression and increased risk of falls when exercise habits were lost. Women were more susceptible to the effects of environmental changes than men in older patients with hypertension.
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Background. Ensitrelvir is a novel oral SARS-CoV-2 3C-like protease inhibitor, and under late clinical development stage for COVID-19 diseases. Ensitrelvir exhibited an inhibition potency for organic cation transporter 1 (OCT1) and multidrug and toxin extrusion protein 1 (MATE1) in in vitro study and clinical drug-drug interaction (DDI) study is required judging fromDDI guidance.Metformin is widely used for treatment of diabetes, and is a sensitive substrate for OCT1 and MATE1. We evaluated the effect of ensitrelvir on the pharmacokinetics (PK) ofmetformin with physiologically-based pharmacokinetic (PBPK) modeling and simulation and clinical DDI study. Methods. The PBPK model of ensitrelvir was developed based on the physicochemical parameters, in vitro transporter inhibition parameters, and estimated PK parameters for human. DDI simulations between ensitrelvir and metformin were performed. Simcyp PBPK Simulator (Version 20, Certara UK Limited, UK) was used to develop PBPK model and simulate the DDIs. The in vitro 50% inhibitory concentration (IC50) values of each transporter were used as inhibition constant (Ki) for DDI simulations. Based on the PBPK analysis, the clinical DDI study planed. Results. PBPK analysis: As the result of DDI simulation, ensitrelvir increased the area under the curve (AUC) of metformin by 12%. The result suggests that in vivo DDI potency of ensitrelvir via inhibition of OCT1 or MATE1 would be low at a single dose of ensitrelvir 1000 mg. Clinical DDI study: The plasma concentration-time profile of metformin and ensitrelvir were monitored after 96 hours from a single dose of metformin with or without ensitrelvir. Ensitrelvir does not have effect on the PK of metformin (a geometric mean of AUC ratio was 1.02, Japanese healthy subjects, N=14), suggesting no MATE1 and OCT1 inhibition by ensitrelvir at a clinical dose. The PBPK analysis could well predict the clinical DDI study result. Conclusion. The results of PBPK analysis and the clinical DDI study suggest that no OCT1 and MATE1 inhibition by ensitrelvir is in the clinical dose. Therefore, ensitrelvir does not have a clinically meaningful effect on the pharmacokinetic profile of OCT1 and/or MATE1 substrates including metformin.
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Background. Ensitrelvir is a new drug candidate to treat COVID-19 disease. According to the in vitro drug-drug interaction (DDI) study, time-dependent inhibition by ensitrelvir was observed on cytochrome P450 3A (CYP3A). The purpose of this study was to evaluate the effect of ensitrelvir on the pharmacokinetics (PK) of CYP3A substrates by clinial DDI studies and physiologically-based pharmacokinetic (PBPK) analyses. Methods. Clinical studies: The effect of once daily multiple-doses of ensitrelvir with the loading dose on Day 1/ maintenance dose (750/250 mg) for 6 days on the PK of midazolam (MDZ) was assessed. MDZ was administered on Days -2 and 6. The effects of once daily multiple-doses of ensitrelvir with 750/250 mg for 5 days on the PK of dexamethasone (DXS) and prednisolone (PLS) were also assessed because these corticosteroids were also CYP3A substrates. DXS and PLS were administered on Days -2, 5 (co-administration with ensitrelvir), 9 and 14 to evaluate the effects after the last dose of ensitrelvir. PBPK analyses: The effects of once daily multiple-doses of ensitrelvir with another dose regimen (the loading dose/mentenance dose [375/125 mg] for 5 days) on the PK of CYP3A substrates were predicted using Simcyp PBPK Simulator (Version 20, Certara UK Limited, UK). Results. The AUC0-inf of MDZ co-administered with ensitrelvir was increased by 8.80-fold compared to those of MDZ alone, indicating that ensitrelvir is a strong CYP3A inhibitor with 750/250 mg for 6 days. The AUC0-inf of DXS on Day 5 was increased 3.47-fold and the effect of ensitrelvir on the PK of DXS was diminished over time after the last dose of ensitrelvir. The AUC0-inf of PLS on Day 5 was increased 1.25-fold and no clinically meaningful effect of ensitrelvir on the PK of PLS was observed. The PBPK analyses predicted that the co-administration of ensitrelvir increased the AUC of MDZ by 3.83-fold and the AUC of DXS by 2.49-fold following ensitrelvir at 375/125 mg for 5 days. A clinical study with MDZ under the analyses conditions is underway to confirm the PBPK results. Conclusion. The clinical study revealed that ensitrelvir affects the PK of CYP3A substrates with 750/250 mg for 5 or 6 days. The PBPK analyses suggests that ensitrelvir is expected to a moderate inhibitor of CYP3A with 375/125 mg for 5 days.
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Background: During the COVID-19 pandemic, cancer patients became reluctant to come to the hospital, receive cancer treatment, and were willing to interrupt or postpone treatment due to concerns about infection. The purpose of this study was to discuss effective treatment strategy decision making support for cancer patients during the COVID-19 pandemic. Methods: An online survey was conducted on decision making support among nurses who worked at a cancer care hospital in Japan from May to July 2021. Results: Forty-nine facilities were asked to participate in the survey, and replies were received from 728 respondents;185 (26.8%) were nurses engaged in the decision making. The most common treatment choice was postponement in 132 patients (73.3%). Nurses who “provided information on measures to prevent COVID-19 infection” were more likely to recognize that “the patient was satisfied with the treatment” (p < 0.05). Nurses who “listened to the patient's thoughts” were less likely to perceive that the patient was “not convinced and continued with the previous treatment” (p < 0.05). Nurses who “listened to the patient's intentions and thoughts after the decision was made,” “followed up on the patient's symptoms and changes in perceptions by telephone,” “followed up on the patient's symptoms and changes in perceptions by videophone”, and “assured the patient that they could take immediate action if symptoms worsened with the physician's permission” more often recognized that the patient “accepted the treatment recommended by the physician although they were not convinced” (p < 0.05). Conclusions: Effective treatment strategy decision making support for cancer patients during the COVID-19 pandemic includes lifestyle guidance for infection prevention, listening to identify the reasons behind patients' choices, and telenursing for follow-up decision.
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Wearing masks and social distancing have become the norm during the COVID-19 pandemic. However, these are increasingly seen as a source of frustration in face-to-face communications. While efforts have been made to overcome these impediments to communication, they typically focus on recovering lost communication quality. Herein, we envision a future where everyone augments their vision using face masks with Augmented Reality capabilities, such that people can conduct safe and expressive face-to-face communication in public. To speculate on this vision, we developed an AR mask prototype which can overlay dynamic virtual "masks"on other users. The virtual mask is dynamic in that it accelerates towards any observer who approaches the wearer. Using this system, we conducted an explorative study to further our speculations on the impact of ubiquitous AR technologies. © 2022 ACM.
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The Japan ACM SIGCHI Chapter and CHI2020 Japan Chapter local meeting committee reports on the online presentation of the Japan local meeting of ACM CHI2020, which was cancelled due to a new coronavirus disease (COVID-19). © 2020 Japan Society for Software Science and Technology. All rights reserved.