Protein corona-mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses.

BACKGROUND: Nanoparticle (NP)-based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and their effect on the functional properties of NPs is poorly understood. OBJECTIVES: We analyzed the relevance of the protein corona on cell type-selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy. METHODS: The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DEX-NPs) was analyzed both in vitro and in vivo. DEX-NPs conjugated with the model antigen ovalbumin (OVA) and immunostimulatory CpG-rich oligodeoxynucleotides were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed. RESULTS: DEX-NPs triggered lectin-induced complement activation, yielding deposition of activated complement factor 3 on the DEX-NP surface. In the spleen DEX-NPs targeted predominantly B cells through complement receptors 1 and 2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than coadministered soluble OVA plus CpG oligodeoxynucleotides. B-cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented induction of anaphylactic shock and allergic asthma accompanied by IgE inhibition. CONCLUSIONS: Opsonization of lectin-coated NPs by activated complement components results in selective B-cell targeting. The intrinsic B-cell targeting property of lectin-coated NPs can be exploited for treatment of allergic immune responses.

New Techniques to Assess In Vitro Release of siRNA from Nanoscale Polyplexes.

PURPOSE: Release of siRNA from nanoscale polyplexes is a crucial yet little investigated process, important during all stages of therapeutic research. Here we develop new methods to characterize polyplex stability early on in the development of new materials. METHODS: We used double fluorescent labeled siRNA to compare binding and stability of a panel of chemically highly diverse nanoscale polyplexes, including peptides, lipids, nanohydrogels, poly-L-lysine brushes, HPMA block copolymers and manganese oxide particles. Conventional EMSA and heparin competition methods were contrasted with a newly developed microscale thermophoresis (MST) assay, a near-equilibrium method that allows free choice of buffer conditions. Integrity of FRET-labeled siRNA was monitored in the presence of nucleases, in cell culture medium and inside living cells. This approach characterizes all relevant steps from polyplex stability, over uptake to in vitro knockdown capability. RESULTS: Diverging polyplex binding properties revealed drawbacks of conventional EMSA and heparin competition assays, where MST and FRET-based siRNA integrity measurements offered a better discrimination of differential binding strength. Since cell culture medium left siRNA in all polyplexes essentially intact, the relevant degradation events could be pinpointed to occur inside cells. Differential binding strength of the variegated polyplexes correlated only partially with intracellular degradation. The most successful compounds in RNAi showed intermediate binding strength in our assays. CONCLUSIONS: We introduce new methods for the efficient and informative characterization of siRNA polyplexes with special attention to stability. Comparing FRET-labeled siRNA in different polyplexes associates successful knockdown with intermediate siRNA stability in various steps from formulation to intracellular persistence.

Selective uptake of cylindrical poly(2-oxazoline) brush-antiDEC205 antibody-OVA antigen conjugates into DEC-positive dendritic cells and subsequent T-cell activation.

To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+) -positive mouse bone marrow-derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205(-) negative BMDC and non-DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen-specific T-cell stimulatory capacity of pretreated BMDC than application of antigen or polymer-antigen conjugate.

A Nationally Representative Summary of 2020 Changes in the Use of Health Care in the United States.

The COVID-19 pandemic produced an unprecedented shock to the U.S. health care system. Prior literature documenting 2020 changes has been limited to certain types of care or subsets of patients. We use the nationally representative Medical Expenditure Panel Survey to summarize changes in all types of health care from 2018 through 2020. Outpatient visits, emergency department visits, and inpatient admissions each fell about 35% in April 2020. Dental visits fell over 80%. Ophthalmology visits declined 71% and mammograms 82%. Psychiatric visits rose slightly (1.6%). By the end of 2020, specialist physician visits recovered, though primary care and dental visits remained 12% lower than 2019.

Adverse Childhood Experiences: Health Care Utilization And Expenditures In Adulthood.

Adverse childhood experiences (ACEs) have been shown to be strong predictors of socioeconomic status, risky health behaviors, chronic health conditions, and adverse outcomes. However, less is known about their association with adult health care utilization and expenditures. We used new data from the 2021 Medical Expenditure Panel Survey-Household Component (MEPS-HC) to provide the first nationally representative estimates of ACEs-related health care utilization and expenditure differences based on direct observation, rather than model-based extrapolation. Compared to demographically similar adults without ACEs, those with ACEs had substantially higher utilization and 26.3 percent higher expenditures. The aggregate spending difference across the 157.6 million US adults with ACEs was $292 billion in 2021. Moreover, we observed large, graded relationships between ACEs and health status, health behaviors, and some dimensions of socioeconomic status. We also found associations between ACEs and a range of adverse adult circumstances, also newly measured in the 2021 MEPS, including financial and housing problems, social network problems, little or no life satisfaction, stress, food insecurity, verbal abuse, physical harm, and discrimination.

COVID-19 Admission Rates and Changes in Care Quality in US Hospitals.

Importance: Unprecedented increases in hospital occupancy rates during COVID-19 surges in 2020 caused concern over hospital care quality for patients without COVID-19. Objective: To examine changes in hospital nonsurgical care quality for patients without COVID-19 during periods of high and low COVID-19 admissions. Design, Setting, and Participants: This cross-sectional study used data from the 2019 and 2020 Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases. Data were obtained for all nonfederal, acute care hospitals in 36 states with admissions in 2019 and 2020, and patients without a diagnosis of COVID-19 or pneumonia who were at risk for selected quality indicators were included. The data analysis was performed between January 1, 2023, and March 15, 2024. Exposure: Each hospital and week in 2020 was categorized based on the number of COVID-19 admissions per 100 beds: less than 1.0, 1.0 to 4.9, 5.0 to 9.9, 10.0 to 14.9, and 15.0 or greater. Main Outcomes and Measures: The main outcomes were rates of adverse outcomes for selected quality indicators, including pressure ulcers and in-hospital mortality for acute myocardial infarction, heart failure, acute stroke, gastrointestinal hemorrhage, hip fracture, and percutaneous coronary intervention. Changes in 2020 compared with 2019 were calculated for each level of the weekly COVID-19 admission rate, adjusting for case-mix and hospital-month fixed effects. Changes during weeks with high COVID-19 admissions (≥15 per 100 beds) were compared with changes during weeks with low COVID-19 admissions (<1 per 100 beds). Results: The analysis included 19 111 629 discharges (50.3% female; mean [SD] age, 63.0 [18.0] years) from 3283 hospitals in 36 states. In weeks 18 to 48 of 2020, 35 851 hospital-weeks (36.7%) had low COVID-19 admission rates, and 8094 (8.3%) had high rates. Quality indicators for patients without COVID-19 significantly worsened in 2020 during weeks with high vs low COVID-19 admissions. Pressure ulcer rates increased by 0.09 per 1000 admissions (95% CI, 0.01-0.17 per 1000 admissions; relative change, 24.3%), heart failure mortality increased by 0.40 per 100 admissions (95% CI, 0.18-0.63 per 100 admissions; relative change, 21.1%), hip fracture mortality increased by 0.40 per 100 admissions (95% CI, 0.04-0.77 per 100 admissions; relative change, 29.4%), and a weighted mean of mortality for the selected indicators increased by 0.30 per 100 admissions (95% CI, 0.14-0.45 per 100 admissions; relative change, 10.6%). Conclusions and Relevance: In this cross-sectional study, COVID-19 surges were associated with declines in hospital quality, highlighting the importance of identifying and implementing strategies to maintain care quality during periods of high hospital use.

Health status, risk factors, and medical conditions among persons enrolled in Medicaid vs uninsured low-income adults potentially eligible for Medicaid under the Affordable Care Act.

IMPORTANCE: Under the Affordable Care Act (ACA), states can extend Medicaid eligibility to nearly all adults with income no more than 138% of the federal poverty level. Uncertainty exists regarding the scope of medical services required for new enrollees. OBJECTIVE: To document the health care needs and health risks of uninsured adults who could gain Medicaid coverage under the ACA. These data will help physicians, other clinicians, and state Medicaid programs prepare for the possible expansions. DESIGN, SETTING, AND PATIENTS: Data from the National Health and Nutrition Examination Survey 2007-2010 were used to analyze health conditions among a nationally representative sample of 1042 uninsured adults aged 19 through 64 years with income no more than 138% of the federal poverty level, compared with 471 low-income adults currently enrolled in Medicaid. MAIN OUTCOMES AND MEASURES: Prevalence and control of diabetes, hypertension, and hypercholesterolemia based on examinations and laboratory tests, measures of self-reported health status including medical conditions, and risk factors such as measured obesity status. RESULTS: Compared with those already enrolled in Medicaid, uninsured adults were less likely to be obese and sedentary and less likely to report a physical, mental, or emotional limitation. They also were less likely to have several chronic conditions. For example, 30.1% (95% CI, 26.8%-33.4%) of uninsured adults had hypertension, hypercholesterolemia, or diabetes compared with 38.6% (95% CI, 32.0%-45.3%) of those enrolled in Medicaid (P = .02). However, if they had these conditions, uninsured adults were less likely to be aware of them and less likely to have them controlled. For example, 80.1% (95% CI, 75.2%-85.1%) of the uninsured adults with at least 1 of these 3 conditions had at least 1 uncontrolled condition, compared with 63.4% (95% CI, 53.7%-73.1%) of adults enrolled in Medicaid. CONCLUSION AND RELEVANCE: Compared with adults currently enrolled in Medicaid, uninsured low-income adults potentially eligible to enroll in Medicaid under the ACA had a lower prevalence of many chronic conditions. A substantial proportion of currently uninsured adults with chronic conditions did not have good disease control; projections based on sample weighting suggest this may represent 3.5 million persons (95% CI, 2.9 million-4.2 million). These adults may need initial intensive medical care following Medicaid enrollment.

COVID-19 Admission Rates and Changes in US Hospital Inpatient and Intensive Care Unit Occupancy.

Importance: The COVID-19 pandemic had unprecedented effects on hospital occupancy, with consequences for hospital operations and patient care. Previous studies of occupancy during COVID-19 have been limited to small samples of hospitals. Objective: To measure the association between COVID-19 admission rates and hospital occupancy in different US areas and at different time periods during 2020. Design, Setting, and Participants: This cross-sectional study used data from the Healthcare Cost and Utilization Project State Inpatient Databases (2019-2020) for patients in nonfederal acute care hospitals in 45 US states, including the District of Columbia. Data analysis was performed between September 1, 2022, and April 30, 2023. Exposures: Each hospital and week in 2020 was categorized based on the number of COVID-19 admissions per 100 beds (<1 [low], 1-4.9, 5-9.9, 10-14.9, or ≥15 [high]). Main Outcomes and Measures: The main outcomes were inpatient and intensive care unit (ICU) occupancy. We used regression analysis to estimate the average change in occupancy for each hospital-week in 2020 relative to the same hospital week in 2019. Results: This study included 3960 hospitals and 54 355 916 admissions. Of the admissions in the 40 states used for race and ethnicity analyses, 15.7% were for Black patients, 12.9% were for Hispanic patients, 62.5% were for White patients, and 7.2% were for patients of other race or ethnicity; 1.7% of patients were missing these data. Weekly COVID-19 admission rates in 2020 were less than 4 per 100 beds for 63.9% of hospital-weeks and at least 10 in only 15.9% of hospital-weeks. Inpatient occupancy decreased by 12.7% (95% CI, 12.1% to 13.4%) during weeks with low COVID-19 admission rates and increased by 7.9% (95% CI, 6.8% to 9.0%) during weeks with high COVID-19 admission rates. Intensive care unit occupancy rates increased by 67.8% (95% CI, 60.5% to 75.3%) during weeks with high COVID-19 admissions. Increases in ICU occupancy were greatest when weighted to reflect the experience of Hispanic patients. Changes in occupancy were most pronounced early in the pandemic. During weeks with high COVID-19 admissions, occupancy decreased for many service lines, with occupancy by surgical patients declining by 43.1% (95% CI, 38.6% to 47.2%) early in the pandemic. Conclusions and Relevance: In this cross-sectional study of US hospital discharges in 45 states in 2020, hospital occupancy decreased during weeks with low COVID-19 admissions and increased during weeks with high COVID-19 admissions, with the largest changes occurring early in the pandemic. These findings suggest that surges in COVID-19 strained ICUs and were associated with large decreases in the number of surgical patients. These occupancy fluctuations may have affected quality of care and hospital finances.

Emergency department volume and racial and ethnic differences in waiting times in the United States.

BACKGROUND: Racial and ethnic differences in emergency department (ED) waiting times have been observed previously. OBJECTIVES: We explored how adjusting for ED attributes, particularly visit volume, affected racial/ethnic differences in waiting time. RESEARCH DESIGN: We constructed linear models using generalized estimating equations with 2007-2008 National Hospital Ambulatory Medical Care Survey data. SUBJECTS: We analyzed data from 54,819 visits to 431 US EDs. MEASURES: Our dependent variable was waiting time, measured from arrival to time seen by physician, and was log transformed because it was skewed. Primary independent variables were individual race/ethnicity (Hispanic and non-Hispanic white, black, other) and ED race/ethnicity composition (covariates for percentages of Hispanics, blacks, and others). Covariates included patient age, triage assessment, arrival by ambulance, payment source, volume, region, and teaching hospital. RESULTS: Geometric mean waiting times were 27.3, 37.7, and 32.7 minutes for visits by white, black, and Hispanic patients. Patients waited significantly longer at EDs serving higher percentages of black patients; per 25 point increase in percent black patients served, waiting times increased by 23% (unadjusted) and 13% (adjusted). Within EDs, black patients waited 9% (unadjusted) and 4% (adjusted) longer than whites. The ED attribute most strongly associated with waiting times was visit volume. Waiting times were about half as long at low-volume compared with high-volume EDs (P<0.001). For Hispanic patients, differences were smaller and less robust to model choice. CONCLUSIONS: Non-Hispanic black patients wait longer for ED care than whites primarily because of where they receive that care. ED volume may explain some across-ED differences.

Exogenous predictors of national performance measures for emergency department crowding.

STUDY OBJECTIVE: We explore the relationship between exogenous-level predictors and performance on 4 emergency department (ED) throughput measures approved by the National Quality Forum: median ED length of visit for admitted and discharged patients, median waiting time, and rate of left without being seen. We seek to find predictors for benchmarking and public reporting. METHODS: This was a study of 424 US hospitals that reported data to the National Hospital Ambulatory Care Survey in 2008 to 2009. Wald F tests and generalized linear models were used to test the relationship between exogenous variables (case mix, age mix, ED volume, teaching status, and Metropolitan Statistical Area status) and performance on the measures. RESULTS: Median waiting time was 35 minutes (95% confidence interval [CI] 26 to 43 minutes), median length of visit for patients treated but not admitted was 131 minutes (95% CI 121 to 142 minutes), median length of visit for patients admitted was 244 minutes (95% CI 218 to 270 minutes), and rate of left without being seen was 1.3% (95% CI 0.9% to 1.8%). Most exogenous variables, including ED volume, Metropolitan Statistical Area, teaching hospital status, age mix, and case mix, demonstrated significant association with waiting times and lengths of visit. Older age and a higher proportion of respiratory complaints were associated with differences in rates of left without being seen. CONCLUSION: Several exogenous factors outside of a hospital's control are associated with National Quality Forum-approved ED performance measures, which will have important implications for future benchmarking and public reporting of these data.

Health service use among the previously uninsured: is subsidized health insurance enough?

Although it has been shown that gaining Medicare coverage at age 65 years increases health service use among the uninsured, difficulty in changing habits or differences in the characteristics of previously uninsured compared with insured individuals may mean that the previously uninsured continue to use the healthcare system differently from others. This study uses Medicare claims data linked to two different surveys--the National Health Interview Survey and the Health and Retirement Study--to describe the relationship between insurance status before age 65 years and the use of Medicare-covered services beginning at age 65 years. Although we do not find statistically significant differences in Medicare expenditures or in the number of hospitalizations by previous insurance status, we do find that individuals who were uninsured before age 65 years continue to use the healthcare system differently from those who were privately insured. Specifically, they have 16% fewer visits to office-based physicians but make 18% and 43% more visits to hospital emergency and outpatient departments, respectively. A key question for the future may be why the previously uninsured seem to continue to use the healthcare system differently from the previously insured. This question may be important to consider as health coverage expansions are implemented.

Experience and education of home health administrators and nursing home administrators and the relationship to establishment ownership.

Administrators in long-term care may have an important influence on quality of care. Limited prior research has described the characteristics of nursing home administrators. Despite growing emphasis on home health care as an alternative to nursing homes, almost no research has described the characteristics of administrators of home health agencies. Using the 2004 National Nursing Home Survey and the 2007 National Home and Hospice Care Survey, we describe the career experience of administrators, and examine the relationship between experience and education of administrators both within and across the nursing home and home health sectors. We also explore the characteristics of nursing homes and home health agencies, including establishment ownership (e.g., nonchain not-for-profit), that are associated with being able to attract administrators with the most experience. We find that home health administrators have, on average, less experience than nursing home administrators. Among home health agencies, administrators with the least experience also tend to have less education. In nursing homes, administrators with less experience tend to have more education. Results from multivariate analysis suggest that chain for-profits may be the least able to attract experienced administrators. More research on the effects of different levels of experience and education among administrators is needed.

Eligibility for and Enrollment in Medicaid Among Nonelderly Adults After Implementation of the Affordable Care Act.

The Affordable Care Act's (ACA) Medicaid expansion resulted in substantial gains in coverage. However, little research has documented eligibility or participation rates among eligible adults in the post-ACA period in part because of the complexities involved in assigning eligibility status. We used simulation modeling to examine Medicaid eligibility and participation during 2014 to 2017. More than one in five adults were Medicaid eligible in expansion states in the post-ACA period. In contrast, about one in 30 adults were Medicaid eligible in nonexpansion states. While eligibility rates differed substantially by expansion status, participation rates among Medicaid-eligible adults were similar in both sets of states (44% to 46%). These estimates indicate that differences in eligibility rather than in participation rates explained differences in enrollment between expansion and nonexpansion states during the study period. Participation in Medicaid is expected to grow during the coronavirus pandemic. Our study provides baseline estimates for future analyses of enrollment trends.

Association Between Medicaid Dental Payment Policies and Children's Dental Visits, Oral Health, and School Absences.

Importance: Although all state Medicaid programs cover children's dental services, less than half of publicly insured children receive recommended care. Objective: To evaluate the association between the ratio of Medicaid payment rates to dentist charges for an index of services (fee ratio) and children's preventive dental visits, oral health, and school absences. Design, Setting, and Participants: In this cross-sectional study, a difference-in-differences analysis was conducted between September 2021 and April 2022 of 15 738 Medicaid-enrolled children and a control group of 16 867 privately insured children aged 6 to 17 years who participated in the 2016-2019 National Survey of Children's Health. Exploratory subgroup analyses by sex and race and ethnicity were also performed. A 2-sided P < .05 was considered significant. Main Outcomes and Measures: Past-year preventive dental visits (at least 1 and at least 2), parent-reported excellent oral health, and number of days absent from school (at least 4 days and at least 7 days). Results: The Medicaid-enrolled sample included a weighted estimate of 51.20% boys and 48.80% girls (mean age, 11.24 years; Black, 21.65%; Hispanic, 37.75%; White, 31.45%). By weighted baseline estimates, 87% and 48% of Medicaid-enrolled children had at least 1 and at least 2 past-year dental visits, respectively, and 29% had parent-reported excellent oral health. Increasing the fee ratio by 1 percentage point was associated with percentage point increases of 0.18 in at least 1 dental visit (95% CI, 0.07-0.30), 0.27 in at least 2 visits (95% CI, 0.04-0.51), and 0.19 in excellent oral health (95% CI, 0.01-0.36). Increases in at least 2 visits were larger for Hispanic children than for White children. By weighted baseline estimates, 28% and 15% of Medicaid-enrolled children had at least 4 and at least 7 past-year school absences, respectively. Regression estimates for school absences were not statistically significant for the full sample but were estimated to be significantly reduced among girls. Conclusions and Relevance: This cross-sectional study found that more generous Medicaid payment policies were associated with significant but modest increases in children's preventive dental visits and excellent oral health. Further research is needed to understand the potential association between policies that improve access to dental care and children's academic success.