The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

Probabilistic forecasts of international bilateral migration flows.

We propose a method for forecasting global human migration flows. A Bayesian hierarchical model is used to make probabilistic projections of the 39,800 bilateral migration flows among the 200 most populous countries. We generate out-of-sample forecasts for all bilateral flows for the 2015 to 2020 period, using models fitted to bilateral migration flows for five 5-y periods from 1990 to 1995 through 2010 to 2015. We find that the model produces well-calibrated out-of-sample forecasts of bilateral flows, as well as total country-level inflows, outflows, and net flows. The mean absolute error decreased by 61% using our method, compared to a leading model of international migration. Out-of-sample analysis indicated that simple methods for forecasting migration flows offered accurate projections of bilateral migration flows in the near term. Our method matched or improved on the out-of-sample performance using these simple deterministic alternatives, while also accurately assessing uncertainty. We integrate the migration flow forecasting model into a fully probabilistic population projection model to generate bilateral migration flow forecasts by age and sex for all flows from 2020 to 2025 through 2040 to 2045.

Accuracy of Doppler blood pressure measurement in HeartMate 3 ventricular assist device patients.

AIMS: Optimal blood pressure (BP) control is imperative to reduce complications, especially strokes, in continuous flow ventricular assist device (VAD) patients. Doppler BP has been shown to be an accurate and reliable non-invasive BP measurement method in HeartMate II and HVAD patients. We examined whether Doppler BP is also accurate in patients with the HeartMate 3 VAD. METHODS AND RESULTS: In a prospective, longitudinal cohort of HeartMate 3 patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Correlation and agreement between Doppler opening pressure and arterial line mean arterial pressure (MAP) versus systolic blood pressure (SBP) were analysed, as well as the effect of pulse pressure on the accuracy of Doppler opening pressure. A total of 589 pairs of simultaneous Doppler opening pressure and arterial line pressure readings were obtained in 43 patients. Doppler opening pressure had good correlation with intra-arterial MAP (r = 0.754) and more closely approximated MAP than SBP (mean error 2.0 vs. -8.6 mmHg). Pulse pressure did not have a clinically significant impact on the accuracy of the Doppler BP method. These results in HeartMate 3 patients are very similar to previous results in HeartMate II and HVAD patients. CONCLUSIONS: Doppler BP method should be the default non-invasive BP measurement method in continuous flow VAD patients including patients implanted with the HeartMate 3.

Accuracy of Doppler blood pressure measurement in continuous-flow left ventricular assist device patients.

AIMS: Accurate blood pressure (BP) measurement in continuous-flow ventricular assist device (CF-VAD) patients is imperative to reduce stroke risk. This study assesses the accuracy of the Doppler opening pressure method compared with the gold standard arterial line method in CF-VAD patients. METHODS AND RESULTS: In a longitudinal cohort of HeartMate II and HVAD patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Overall correlation, agreement between Doppler opening pressure and arterial line mean vs. systolic pressure, and the effect of arterial pulsatility on the accuracy of Doppler opening pressure were analysed. A total of 1933 pairs of Doppler opening pressure and arterial line pressure readings within 1 min of each other were identified in 154 patients (20% women, mean age 55 ± 15, 50% HeartMate II and 50% HVAD). Doppler opening pressure had good correlation with invasive mean arterial pressure (r = 0.742, P < 0.0001) and more closely approximated mean than systolic BP (mean error 2.4 vs. -8.4 mmHg). Arterial pulsatility did not have a clinically significant effect on the accuracy of the Doppler opening pressure method. CONCLUSIONS: Doppler opening pressure should be the standard non-invasive method of BP measurement in CF-VAD patients.

Non-invasive label-free monitoring the cardiac differentiation of human embryonic stem cells in-vitro by Raman spectroscopy.

BACKGROUND: Online label-free monitoring of in-vitro differentiation of stem cells remains a major challenge in stem cell research. In this paper we report the use of Raman micro-spectroscopy (RMS) to measure time- and spatially-resolved molecular changes in intact embryoid bodies (EBs) during in-vitro cardiogenic differentiation. METHODS: EBs formed by aggregation of human embryonic stem cells (hESCs) were cultured in defined medium to induce differentiation towards cardiac phenotype and maintained in purpose-built micro-bioreactors on the Raman microscope for 5days (between days 5 and 9 of differentiation) and spatially-resolved spectra were recorded at 24h intervals. RESULTS: The Raman spectra showed that the onset of spontaneous beating of EBs at day 7 coincided with an increase in the intensity of the Raman bands at 1340cm(-1), 1083cm(-1), 937cm(-1), 858cm(-1), 577cm(-1) and 482cm(-1). The spectral maps corresponding to these bands had a high positive correlation with the expression of the cardiac-specific α-actinin obtained by immuno-fluorescence imaging of the same EBs. The spectral markers obtained here are also in agreement with previous studies performed on individual live hESC-derived CMs. CONCLUSIONS: The intensity profile of these Raman bands can be used for label-free in-situ monitoring of EBs to estimate the efficacy of cardiogenic differentiation. GENERAL SIGNIFICANCE: As the acquisition of the time-course Raman spectra did not affect the viability or the differentiation potential of the hESCs, this study demonstrates the feasibility of using RMS for on-line non-invasive continuous monitoring of such processes inside bioreactor culture systems.

Noninvasive detection and imaging of molecular markers in live cardiomyocytes derived from human embryonic stem cells.

Raman microspectroscopy (RMS) was used to detect and image molecular markers specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs). This technique is noninvasive and thus can be used to discriminate individual live CMs within highly heterogeneous cell populations. Principal component analysis (PCA) of the Raman spectra was used to build a classification model for identification of individual CMs. Retrospective immunostaining imaging was used as the gold standard for phenotypic identification of each cell. We were able to discriminate CMs from other phenotypes with >97% specificity and >96% sensitivity, as calculated with the use of cross-validation algorithms (target 100% specificity). A comparison between Raman spectral images corresponding to selected Raman bands identified by the PCA model and immunostaining of the same cells allowed assignment of the Raman spectral markers. We conclude that glycogen is responsible for the discrimination of CMs, whereas myofibril proteins have a lesser contribution. This study demonstrates the potential of RMS for allowing the noninvasive phenotypic identification of hESC progeny. With further development, such label-free optical techniques may enable the separation of high-purity cell populations with mature phenotypes, and provide repeated measurements to monitor time-dependent molecular changes in live hESCs during differentiation in vitro.

Satisfaction and dysphotopsia in the pseudophakic patient.

OBJECTIVE: To examine factors that influence satisfaction after uncomplicated cataract surgery. DESIGN: Retrospective case review and examination of patients. PARTICIPANTS: Sixty-one consecutive patients, seen at the John A. Moran Eye Center, University of Utah School of Medicine, who had uncomplicated cataract surgery from 1 practice and 40 consecutive control patients who met the inclusion criteria and were willing to participate. METHODS: Inclusion criteria were best-corrected visual acuity (BCVA) of at least 20/20, without any ocular disease that might affect vision. Patients were given a complete ophthalmic examination, had photos of the intraocular lens (IOL) and capsule taken, and were asked questions about dysphotopsia and satisfaction. A group of patients >65 years old with 20/20 BCVA and without other ophthalmic diagnoses were recruited, asked the same questions, and compared. RESULTS: The only significant correlation with dissatisfaction was dysphotopsia (r = 0.602, CI 0.42-0.74, p < 0.0001). BCVA, uncorrected visual acuity, posterior capsular opacification, and anterior capsule overlap of the optic were not significantly correlated. The IOL patients were significantly worse for reported glare (p < 0.0001), photophobia (p < 0.0001), and flashes of light (p = 0.0002), but not for halos. CONCLUSIONS: While satisfaction with cataract removal and IOL placement is high, dysphotopsia is the most important contributor to dissatisfaction and is relatively common. Furthermore, these symptoms are much worse than in age-matched controls. Research seeking to ameliorate dysphotopsia is clinically important.

Predicting biodiversity change: outside the climate envelope, beyond the species-area curve.

Efforts to anticipate threats to biodiversity take the form of species richness predictions (SRPs) based on simple correlations with current climate and habitat area. We review the major approaches that have been used for SRP, species-area curves and climate envelopes, and suggest that alternative research efforts may provide more understanding and guidance for management. Extinction prediction suffers from a number of limitations related to data and the novelty of future environments. We suggest additional attention to (1) identification of variables related to biodiversity that are diagnostic and potentially more predictable than extinction, (2) constraints on species dispersal and reproduction that will determine population persistence and range shifts, including limited sources or potential immigrants for many regions, and (3) changes in biotic interactions and phenology. We suggest combinations of observational and experimental approaches within a framework available for ingesting heterogeneous data sources. Together, these recommendations amount to a shift in emphasis from prediction of extinction numbers to identification of vulnerabilities and leading indicators of change, as well as suggestions for surveillance tools needed to evaluate important variables and the experiments likely to provide most insight.