Is the Gap Closing? Comparison of Sociodemographic Disparities in COVID-19 Hospitalizations and Outcomes Between Two Temporal Waves of Admissions.

OBJECTIVE: The COVID-19 pandemic has disproportionately impacted minority communities, yet little data exists regarding whether disparities have improved at a health system level. This study examined whether sociodemographic disparities in hospitalization and clinical outcomes changed between two temporal waves of hospitalized COVID-19 patients. METHODS: This is a retrospective cohort study of primary care patients at Mass General Brigham (a large northeastern health system serving 1.27 million primary care patients) hospitalized in-system with COVID-19 between March 1, 2020, and March 1, 2021, categorized into two 6-month "wave" periods. We used chi-square tests to compare demographics between waves, and regression analysis to characterize the association of race/ethnicity and language with in-hospital severe outcomes (death, hospice discharge, intensive unit care need). RESULTS: Hispanic/Latino, Black, and non-English-speaking patients constituted 30.3%, 12.5%, and 29.7% of COVID-19 admissions in wave 1 (N = 5844) and 22.2%, 9.0%, and 22.7% in wave 2 (N = 4007), compared to 2019 general admission proportions of 8.8%, 6.3%, and 7.7%, respectively. Admissions from highly socially vulnerable census tracts decreased between waves. Non-English speakers had significantly higher odds of severe illness during wave 1 (OR 1.35; 95% CI: 1.10, 1.66) compared to English speakers; this association was non-significant during wave 2 (OR 1.01; 95% CI: 0.76, 1.36). CONCLUSIONS: Comparing two COVID-19 temporal waves, significant sociodemographic disparities in COVID-19 admissions improved between waves but continued to persist over a year, demonstrating the need for ongoing interventions to truly close equity gaps. Non-English-speaking language status independently predicted worse hospitalization outcomes in wave 1, underscoring the importance of targeted and effective in-hospital supports for non-English speakers.

Changes in hospital admissions for urgent conditions during COVID-19 pandemic.

OBJECTIVES: To determine whether patients are deferring necessary care for urgent conditions during the coronavirus disease 2019 (COVID-19) pandemic and, if so, to what extent. STUDY DESIGN: Cross-sectional study. METHODS: Using billing data from 8 acute care hospitals, we identified 9 principal medical diagnoses from International Classification of Diseases, Tenth Revision codes across 4 medical specialties (cardiology, gastroenterology, neurology, and urology). In addition, we defined a combined obstetrical falsification end point. We compared daily admission rates during the pandemic period (3/1/2020-4/30/2020) with the same dates in 2019 (3/1/2019-4/30/2019). As a reference, we also compared a prepandemic period in the same years (1/1/2019-2/28/2019 and 1/1/2020-2/29/2020). We compared admission rates between years using t tests. RESULTS: There were 3219 admissions for the conditions of interest during the study period in 2019 and 2661 in 2020. There was no difference in prepandemic daily admission rates in 2020 compared with 2019 (29.04 vs 27.63 admissions per day; -4.9%; P = .50). During the pandemic period, there was a 33.7% decrease in admission rates for all conditions combined in 2020 compared with 2019 (24.68 vs 16.37; -33.7%; P = .03). By specialty, the combined gastroenterology (10.22 vs 7.20; -29.6%; P = .02) and cardiovascular (2.34 vs 1.29; -44.7%; P = .05) end points demonstrated reduction in daily admission rates. CONCLUSIONS: Daily admission rates during the COVID-19 pandemic were lower for these acute medical conditions. Public awareness campaigns are urgently needed to reassure the public about the safety of presenting for care.

In situ nuclear morphology measurements using light scattering as biomarkers of neoplastic change in animal models of carcinogenesis.

Light scattering spectroscopy measurements can be used to determine the structure of tissue samples. Through refined data acquisition and signal processing techniques, quantitative nuclear morphology measurements may be obtained from light scattering data. These data have been used primarily as a biomarker of neoplastic change in a wide range of settings. Here, we review the application of light scattering to assessing the health status of tissues drawn from animal models of carcinogenesis, in particular, the rat esophagus and the golden Syrian hamster trachea carcinogenesis models. In addition, we present results from ex vivo human tissues to demonstrate the relevance of the use of animal models which are excellent surrogates for several human cancers. These models provide the opportunity to develop biomarkers and test chemopreventive and therapy strategies before application in humans.

Application of Mie theory to determine the structure of spheroidal scatterers in biological materials.

We present here the results of a numerical study on light scattering from nonspherical particles with relevance to detecting precancerous states in epithelial tissues. In previous studies of epithelial cell nuclei, the experimental light scattering data have been analyzed by comparison with Mie theory. However, given the spheroidal shape of many cell nuclei, the validity of this assumption demands a thorough investigation. We investigate this assumption by using the T-matrix method to model light scattered from spheroids with parameters relevant to epithelial cell nuclei. In our previous studies, we have developed a data analysis procedure that extracts the oscillatory component of the angular-scattering distribution for an ensemble of epithelial cell nuclei for comparison with Mie theory. We demonstrate that application of our analysis procedure to the predictions of the T-matrix method for spheroids, oriented such that their axis of symmetry is aligned with the incident light propagation direction, generally yields the spheroid dimension that is transverse to the incident light propagation direction with subwavelength accuracy.

Polarization effects on scatterer sizing accuracy analyzed with frequency-domain angle-resolved low-coherence interferometry.

Angle-resolved low-coherence interferometry (a/LCI) enables us to make depth-resolved measurements of scattered light that can be used to recover subsurface structural information such as the size of cell nuclei. Endoscopic frequency-domain a/LCI (fa/LCI) acquires data by using a novel fiber probe in a fraction of a second, making it a clinically practical system. However, birefringent effects in fiber-based systems can alter the polarization state of the incident light and potentially skew the collected data. We analyze the effect the polarization state of the incident light has on scattering data collected from polystyrene microsphere tissue phantoms and in vitro cell samples and examine the subsequent accuracy of the determined sizes. It is shown that the endoscopic fa/LCI system accurately determines the size of polystyrene microspheres without the need to control the polarization of the incident beam, but that epithelial cell nuclear sizes are accurately determined only when the polarization state of the incident light is well characterized.

In situ assessment of intraepithelial neoplasia in hamster trachea epithelium using angle-resolved low-coherence interferometry.

Optical spectroscopy was used to evaluate the transformation of nuclear morphology associated with intraepithelial neoplasia in an animal model of carcinogenesis. In this pilot study, we have assessed the capability of angle-resolved low-coherence interferometry (a/LCI) to monitor in situ the neoplastic progression of hamster trachea epithelial tissue. By using the depth resolution made possible by coherence gating, the a/LCI system has been adapted to the unique geometry of the hamster trachea to allow us to extract useful nuclear morphometric information from cells in the epithelial layer without the need for exogenous staining or tissue fixation. Analysis of a/LCI nuclear morphology measurements has identified two important biomarkers of neoplastic transformation in hamster trachea epithelium, the size and the refractive index of epithelial cell nuclei. By comparing the a/LCI measurements of these two biomarkers to pathologic classification, we distinguished nuclear morphology changes for normal tissue, low-grade dysplasia, and high-grade dysplasia. Given its previous usefulness for tracking neoplastic change through nuclear morphometry measurements, the a/LCI technique may prove to be a useful tool in evaluating chemopreventive agents in future studies of hamster trachea epithelium.

In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry.

BACKGROUND: Monitoring of patients with Barrett's esophagus (BE) for dysplasia, currently done by systematic biopsy, can be improved through increasing the proportion of at-risk tissue examined. OBJECTIVE: Optical biopsy techniques, which do not remove the tissue but interrogate the tissue with light, offer a potential method to improve the monitoring of BE. Frequency-domain angle resolved low-coherence interferometry (fa/LCI) is an optical spectroscopic technique applied through an endoscopic fiber bundle and measures the depth-resolved nuclear morphology of tissue, a key biomarker for identifying dysplasia. The aim of the study was to assess the diagnostic capability of fa/LCI for differentiating healthy and dysplastic tissue in patients with BE. METHODS: Depth-resolved angular scattering data are acquired by using fa/LCI from tissue excised from 3 patients who had esophagogastrectomy. The data are processed to determine the average nuclear size and density as a function of depth beneath the tissue surface. These data are compared with the pathologic classification of the tissue. MAIN OUTCOME MEASUREMENTS: Average of depth-resolved nuclear diameter and nuclear density measurements in tissue samples. RESULTS: Upon comparison to pathologic diagnosis, the fa/LCI data results report the nuclear atypia characteristic of dysplasia in the epithelial tissue. Examination of the average nuclear morphology over the superficial 150 mum results in complete separation between healthy columnar and BE dysplastic tissues. LIMITATIONS: Lack of in vivo data; lack of nondysplastic BE data because of limited sample size. CONCLUSIONS: In complicated tissue structures, such as BE, depth-resolved nuclear morphology measurements provided an excellent means to identify dysplasia. The preliminary results demonstrate the great potential for the in vivo application of fa/LCI as a targeting mechanism for physical biopsy in patients with BE.

Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) enables depth-resolved measurements of scattered light that can be used to recover subsurface structural information, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed angular data, based on the justification that the coherent scattering must necessarily occur over length scales greater than the cell size. To fully study this effect, results of experiments designed to test the validity of this approach are now presented. The a/LCI technique is used to examine light scattered by regular cell arrays, created using stamped adhesive micropatterned substrates. By varying the array spacing, it is demonstrated that cell-to-cell correlations have a predictable effect on light scattering distributions. These results are compared to image analysis of fluorescence micrographs of the cell array samples. The a/LCI results show that the impact of coherent scattering on nuclear morphology measurements can be eliminated through data filtering.

Fourier-domain angle-resolved low coherence interferometry through an endoscopic fiber bundle for light-scattering spectroscopy.

We present a novel endoscopic fiber bundle probe incorporated in a Fourier-domain angle-resolved low coherence interferometry system for the measurement of depth-resolved angular scattering distributions to permit the determination of scatterer size via elastic scattering properties. Depth resolution is achieved with a superluminescent diode via a Mach-Zehnder interferometer. The sample is illuminated with a collimated beam, and a Fourier plane image of the backscattered light is collected by a coherent fiber bundle. The angular scattering distribution relayed by the fiber bundle is mixed with the reference field and made to coincide with the input slit of an imaging spectrograph. The data collected are processed in real time, producing a depth-resolved angular scattering distribution in 0.37 s. The data are used to determine the sizes of polystyrene microspheres with subwavelength precision and accuracy.

Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry.

Angle-resolved low-coherence interferometry (a/LCI) is used to obtain quantitative, depth-resolved nuclear morphology measurements. We compare the average diameter and texture of cell nuclei in rat esophagus epithelial tissue to grading criteria established in a previous a/LCI study to prospectively grade neoplastic progression. We exploit the depth resolution of a/LCI to exclusively examine the basal layer of the epithelium, approximately 50 to 100 microm beneath the tissue surface, without the need for exogenous contrast agents, tissue sectioning, or fixation. The results of two studies are presented that compare the performance of two a/LCI modalities. Overall, the combined studies show 91% sensitivity and 97% specificity for detecting dysplasia, using histopathology as the standard. In addition, the studies enable the effects of dietary chemopreventive agents, difluoromethylornithine (DFMO) and curcumin, to be assessed by observing modulation in the incidence of neoplastic change. We demonstrate that a/LCI is highly effective for monitoring neoplastic change and can be applied to assessing the efficacy of chemopreventive agents in the rat esophagus.

Improved interferometric detection of scattered light with a 4f imaging system.

We analyze the performance of three imaging systems to detect near-forward scattered light interferometrically by using a Mach-Zehnder geometry. The alignment of each system is demonstrated by measurement of the heterodyne efficiency and correlation of the angular width and field 1/e radius measurements of the sample beam. Measurements of angular-scattering data demonstrate the range of angles over which each system is effective. Of the three systems analyzed, the 4f imaging system is determined to be most effective, because it accurately reproduces both the phase and the amplitude of the scattered field at the detector.

Rapid, depth-resolved light scattering measurements using Fourier domain, angle-resolved low coherence interferometry.

We present a novel angle-resolved low coherence interferometry scheme for rapid measurement of depth-resolved angular scattering distributions to enable determination of scatterer size via elastic scattering properties. Depth resolution is achieved using a superluminescent diode in a modified Mach-Zehnder interferometer with the mixed signal and reference fields dispersed by an imaging spectrograph. The spectrograph slit is located in a Fourier transform plane of the scattering sample, enabling angle-resolved measurements over a 0.21 radian range. The capabilities of the new technique are demonstrated by recording the distribution of light scattered by a sub-surface layer of polystyrene microspheres in 40 milliseconds. The data are used to determine the microsphere size with good accuracy. Future clinical application to measuring the size of cell nuclei in living epithelial tissues using backscattered light is discussed.

Determining nuclear morphology using an improved angle-resolved low coherence interferometry system.

We outline the process for determining the morphology of subsurface epithelial cell nuclei using depth-resolved light scattering measurements. The measurements are accomplished using a second generation angle-resolved low coherence interferometry system. The new system greatly improves data acquisition and analysis times compared to the initial prototype system. The calibration of the new system is demonstrated in scattering studies to determine the size distribution of polystyrene microspheres in a turbid sample. The process for determining the size of cell nuclei is discussed by analyzing measurements of basal cells in a sub-surface layer of intact, unstained epithelial tissue.