BackgroundThe pandemic disrupted the care of patients with rheumatic diseases; difficulties in access to care and its psychological impact affected quality of life. Telemedicine as an alternative to traditional face-to-face office visits has the potential to mitigate this impact.ObjectiveTo evaluate patient and provider experience with telemedicine and its effect on care.MethodsWe surveyed patients with rheumatic diseases and their rheumatology providers. The surveys were conducted in 2020 and repeated in 2021. We assessed data on quality of care and health-related quality of life.ResultsHundred patients and 17 providers responded to the survey. Patients reported higher satisfaction with telemedicine in 2021 compared to 2020 (94 vs. 84%), felt more comfortable with (96 vs. 86%), expressed a stronger preference for (22 vs. 16%), and higher intention to use telemedicine in the future (83 vs. 77%); patients thought physicians were able to address their concerns. While providers' satisfaction with telemedicine increased (18–76%), 14/17 providers believed that telemedicine visits were worse than in-person visits. There were no differences in annualized office visits and admissions. Mean EQ-5D score was 0.74, lower than general population (0.87) but equivalent to a subset of patients with SLE (0.74).ConclusionOur data showed a high level of satisfaction with telemedicine. The lower rheumatology provider satisfaction raises concern if telemedicine constitutes an acceptable alternative to in-person care. The stable number of office visits, admissions, and the similar quality of life to pre-pandemic level suggest effective management of rheumatic diseases using telemedicine/in-person hybrid care.
Monoclonal antibodies (MAbs) have the potential to assist in the battle against multidrug-resistant bacteria such as carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, the characteristics by which these antibodies (Abs) function, such as the role of antibody subclass, must be determined before such modalities can be carried from the bench to the bedside. We performed a subclass switch on anticapsular monoclonal murine IgG3 (mIgG3) hybridomas and identified and purified a murine IgG1 (mIgG1) hybridoma line through sib selection. We then compared the ability of the mIgG1 and mIgG3 antibodies to control CR-Kp sequence type 258 (ST258) infection both in vitro and in vivo. We found by enzyme-limited immunosorbent assay (ELISA) and flow cytometry that mIgG3 has superior binding to the CR-Kp capsular polysaccharide (CPS) and superior agglutinating ability compared to mIgG1. The mIgG3 also, predictably, had better complement-mediated serum bactericidal activity than the mIgG1 and also promoted neutrophil-mediated killing at concentrations lower than that of the mIgG1. In contrast, the mIgG1 had marginally better activity in improving macrophage-mediated phagocytosis. Comparing their activities in a pulmonary infection model with wild-type as well as neutropenic mice, both antibodies reduced organ burden in a nonlethal challenge, regardless of neutrophil status, with mIgG1 having the highest overall burden reduction in both scenarios. However, at a lethal inoculum, both antibodies showed reduced efficacy in neutropenic mice, with mIgG3 retaining the most activity. These findings suggest the viability of monoclonal Ab adjunctive therapy in neutropenic patients that cannot mount their own immune response, while also providing some insight into the relative contributions of immune mediators in CR-Kp protection. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is an urgent public health threat that causes life-threatening infections in immunocompromised hosts. Its resistance to nearly all antibiotics necessitates novel strategies to treat it, including the use of monoclonal antibodies. Monoclonal antibodies are emerging as important adjuncts to traditional pharmaceuticals, and studying how they protect against specific bacteria such as Klebsiella pneumoniae is crucial to their development as effective therapies. Antibody subclass is often overlooked but is a major factor in how an antibody interacts with other mediators of immunity. This paper is the first to examine how the subclass of anticapsular monoclonal antibodies can affect efficacy against CR-Kp. Additionally, this work sheds light on the viability of monoclonal antibody therapy in neutropenic patients, who are most vulnerable to CR-Kp infection.
Monoclonal antibodies (Abs) have the potential to assist in the battle against multidrug-resistant bacteria such as Carbapenem-Resistant Klebsiella pneumoniae (CR-Kp). However, the characteristics by which these Abs function, such as the role of antibody subclass, must be determined before such modalities can be carried from the bench to the bedside. We performed a subclass switch on anti-capsular monoclonal murine IgG3 (mIgG3) hybridomas and identified and purified a murine IgG1 (mIgG1) hybridoma line through sib selection. We then compared the ability of the mIgG1 and mIgG3 antibodies to control CR-Kp ST258 infection both in vitro and in vivo. We found by ELISA and flow cytometry that mIgG3 has superior binding to CR-Kp CPS and superior agglutinating ability compared to mIgG1. The mIgG3 also predictably had better complement-mediated serum bactericidal activity than the mIgG1 and also promoted neutrophil-mediated killing at concentrations lower than the mIgG1. In contrast, the mIgG1 had marginally better activity in improving macrophage-mediated phagocytosis. Comparing their activities in a pulmonary infection model with wild type as well as neutropenic mice, both antibodies reduced organ burden in a non-lethal challenge, regardless of neutrophil status, with mIgG1 having the highest overall burden reduction in both scenarios. However, at a lethal inoculum, both antibodies showed reduced efficacy in neutropenic mice, with mIgG3 retaining the most activity. These findings suggest the viability of monoclonal Ab adjunctive therapy in neutropenic patients that cannot mount their own immune response, while also providing some insight into the relative contributions of immune mediators in CR-Kp protection.ImportanceCarbapenem-resistant Klebsiella pneumoniae is an urgent public health threat that causes life-threatening infections in immunocompromised hosts. Its resistance to nearly all antibiotics necessitates novel strategies to treat it, including the use of monoclonal antibodies. Monoclonal antibodies are emerging as important adjuncts to traditional pharmaceuticals, and studying how they protect against specific bacteria such as Klebsiella pneumoniae is crucial to their development as effective therapies. Antibody subclass is often overlooked but is a major factor in how an antibody interacts with other mediators of immunity. This paper is the first to examine how the subclass of anti-capsular monoclonal antibodies can affect efficacy against CR-Kp. Additionally, this work sheds light on the viability of monoclonal antibody therapy in neutropenic patients, who are most vulnerable to CR-Kp infection.
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