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The clinical benefits of treatments with a combination of two or more therapeutic monoclonal antibodies (mAbs) have emerged in recent years. Imaged capillary isoelectric focusing is a frequently used technology in the biopharmaceutical industry for charge variant analysis of protein therapeutics. However, with the wide concentration ranges of combination products, one component may fall within the linear detection range, whereas the other does not. Here, we report a novel methodology to explore charge variants of mAb mixtures using multiple detection techniques simultaneously. We use ultraviolet absorbance to monitor the charge variants of the high-concentration component and native fluorescence (FL) to monitor the variants of the low-concentration one. Charge variants of mixtures that span 40-fold in ratio differences can be accurately quantified with this approach. In contrast to the conventional methods, it is not necessary to prepare and analyze two samples at different concentrations and combine the results for combination product testing. Additionally, the use of FL detection enables the charge variant analysis of highly potent/low abundant mAbs in a mixture. This methodology is more quality-control friendly and efficient for the charge variant analysis of combination products with wide ratios.

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Adults with obesity may develop asthma that is ineffectively controlled by inhaled corticosteroids and long-acting beta-adrenoceptor agonists. Mechanistic and translational studies suggest that metabolic dysregulation that occurs with obesity, particularly hyperglycemia and insulin resistance, contributes to altered immune cell function and low-grade systemic inflammation. Importantly, in these cases, the same proinflammatory cytokines believed to contribute to insulin resistance may also be responsible for airway remodeling and hyperresponsiveness. In the past decade, new research has emerged assessing whether hypoglycemic therapies impact comorbid asthma as reflected by the incidence of asthma, asthmarelated emergency department visits, asthma-related hospitalizations, and asthma-related exacerbations. The purpose of this review article is to discuss the mechanism of action, preclinical data, and existing clinical studies regarding the efficacy and safety of hypoglycemic therapies for adults with obesity and comorbid asthma.

IMPORTANCE: Due to limitations in data collected through electronic health records, the social risk factors (SRFs) that predate severe illness and restrict access to critical care services are poorly understood. OBJECTIVES: This study explored the feasibility and utility of directly eliciting SRFs in the ICU by implementing a screening program. DESIGN, SETTING, AND PARTICIPANTS: Five hundred sixty-six critically ill patients at the medical ICU of Robert Wood Johnson University Hospital from July 1, 2019, to September 31, 2021, were interviewed for SRFs using an adapted version of the American Academy of Family Physicians’ Social Needs Screening Tool. MAIN OUTCOMES AND MEASURES: For each SRFs, we compared basic demographic factors, proxies of socioeconomic status, and severity score between those with and without the SRFs through chi-square tests and Wilcoxon rank-sum tests. Furthermore, we determined the prevalence of SRFs overall, before, and during the COVID-19 pandemic. RESULTS: Of critically ill patients, 39.58% reported at least one SRF. Age, zip-code matched median household income, and insurance type differed depending on the SRFs. Notably, patients with SRFs were admitted with a lower average severity score, indicating reduced risk in mortality. Since March 2020, the prevalence of SRFs in the ICU overall fell from 54.47% to 35.44%. Conversely, the proportion of patients unable to afford healthcare increased statistically significantly from 7.32% to 18.06%. CONCLUSIONS AND RELEVANCE: Screening for SRFs in the ICU detected the presence of disproportionally low-risk patients whose access to critical care services became restricted throughout the pandemic.

Due to limitations in data collected through electronic health records, the social risk factors (SRF) that predate severe illness and restrict access to critical care services are poorly understood. This study explored the feasibility and utility of directly eliciting SRF in the ICU by implementing a screening program. 566 critically ill patients at the medical ICU of Robert Wood Johnson University Hospital from July 1, 2019, to September 31, 2021, were screened for seven SRF. We compared characteristics between those with and without each SRF through Chi-squared tests and Wilcoxon Rank Sum tests. Overall, 39.58% of critically ill patients reported at least one SRF. Age, socioeconomic status, insurance type, and severity score differed significantly depending on the SRF. Most notably, the prevalence of SRF, overall and individually, changed after March 2020 which represented the onset of the COVID-19 pandemic. Our findings indicate that SRF can induce low-risk severe illnesses and restrict access to critical care services.

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