Abstract
Background
Monitoring COVID-19 testing volumes and test positivity is an integral part of the response to the pandemic. We described the characteristics of individuals who were tested and ...tested positive for SARS-CoV-2 during the pre-vaccine phase of the pandemic in the United States (U.S.).
Methods
This descriptive study analyzed three U.S. electronic health record (EHR) databases (Explorys, Academic Health System, and OneFlorida) between February and November 2020, identifying patients who received an interpretable nucleic acid amplification test (NAAT) result. Test-level data were used to characterize the settings in which tests were administered. Patient-level data were used to calculate test positivity rates and characterize the demographics, comorbidities, and hospitalization rates of COVID-19-positive patients.
Results
Over 40% of tests were conducted in outpatient care settings, with a median time between test order and result of 0–1 day for most settings. Patients tested were mostly female (55.6–57.7%), 18–44 years of age (33.9–41.2%), and Caucasian (44.0–66.7%). The overall test positivity rate was 13.0% in Explorys, 8.0% in Academic Health System, and 8.9% in OneFlorida. The proportion of patients hospitalized within 14 days of a positive COVID-19 NAAT result was 24.2–33.1% across databases, with patients over 75 years demonstrating the highest hospitalization rates (46.7–69.7% of positive tests).
Conclusions
This analysis of COVID-19 testing volume and positivity patterns across three large EHR databases provides insight into the characteristics of COVID-19-tested, COVID-19-test-positive, and hospitalized COVID-19-test-positive patients during the early phase of the pandemic in the U.S.
COVID-19 infections have contributed to substantial increases in hospitalizations. This study describes demographics, baseline clinical characteristics and treatments, and clinical outcomes among ...U.S. patients admitted to hospitals with COVID-19 during the prevaccine phase of the pandemic. A total of 20,446 hospitalized patients with a positive COVID-19 nucleic acid amplification test were identified from three large electronic health record databases during 5 February-30 November 2020 (Academic Health System:
= 4504; Explorys;
= 7492; OneFlorida:
= 8450). Over 90% of patients were ≥30 years of age, with an even distribution between sexes. At least one comorbidity was recorded in 84.6-96.1% of patients; cardiovascular and respiratory conditions (28.8-50.3%) and diabetes (25.6-44.4%) were most common. Anticoagulants were the most frequently reported medications on or up to 28 days after admission (44.5-81.7%). Remdesivir was administered to 14.1-24.6% of patients and increased over time. Patients exhibited higher COVID-19 severity 14 days following admission than the 14 days prior to and on admission. The length of in-patient hospital stay ranged from a median of 4 to 6 days, and over 85% of patients were discharged alive. These results promote understanding of the clinical characteristics and hospital-resource utilization associated with hospitalized COVID-19 over time.
•Assessed background incidence rate of 17 AESI in 6 administrative claims databases.•Background rates varied by database and demographic characteristics.•Rates of most AESI increased with age and ...were higher among males.•AMI (Medicare) and anaphylaxis (all databases) rates showed seasonality.•AESI rates fluctuated in 2020, but most returned to 2019 levels after May 2020.
The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety.
We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020.
The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12–19 per 100,000 person-years), appendicitis (80 vs 117–155), and narcolepsy (38 vs 41–53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March–May 2020 compared with March–May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell’s palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019.
AESI background rates varied by database and demographics and fluctuated in March–December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.
ABSTRACT We investigate anew the distribution of absolute carbon abundance, A(C) = log ϵ(C), for carbon-enhanced metal-poor (CEMP) stars in the halo of the Milky Way, based on high-resolution ...spectroscopic data for a total sample of 305 CEMP stars. The sample includes 147 CEMP-s (and CEMP-r/s) stars, 127 CEMP-no stars, and 31 CEMP stars that are unclassified, based on the currently employed Ba/Fe criterion. We confirm previous claims that the distribution of A(C) for CEMP stars is (at least) bimodal, with newly determined peaks centered on A(C) = 7.96 (the high-C region) and A(C) = 6.28 (the low-C region). A very high fraction of CEMP-s (and CEMP-r/s) stars belongs to the high-C region, while the great majority of CEMP-no stars resides in the low-C region. However, there exists complexity in the morphology of the A(C)-Fe/H space for the CEMP-no stars, a first indication that more than one class of first-generation stellar progenitors may be required to account for their observed abundances. The two groups of CEMP-no stars we identify exhibit clearly different locations in the A(Na)-A(C) and A(Mg)-A(C) spaces, also suggesting multiple progenitors. The clear distinction in A(C) between the CEMP-s (and CEMP-r/s) stars and the CEMP-no stars appears to be as successful, and likely more astrophysically fundamental, for the separation of these sub-classes as the previously recommended criterion based on Ba/Fe (and Ba/Eu) abundance ratios. This result opens the window for its application to present and future large-scale low- and medium-resolution spectroscopic surveys.
In 2019, sands in nearby runoff streams from public beach showers were sampled on three islands in the State of Hawaii and tested for over 18 different petrochemical UV filters. Beach sands that are ...directly in the plume discharge of beach showers on three of the islands of Hawaii (Maui, Oahu, Hawai’i) were found to be contaminated with a wide array of petrochemical-based UV-filters that are found in sunscreens. Sands from beach showers across all three islands had a mean concentration of 5619 ng/g of oxybenzone with the highest concentration of 34,518 ng/g of oxybenzone at a beach shower in the Waikiki area of Honolulu. Octocrylene was detected at a majority of the beach shower locations, with a mean concentration of 296.3 ng/g across 13 sampling sites with the highest concentration of 1075 ng/g at the beach shower in Waikiki. Avobenzone, octinoxate, 4-methylbenzylidene camphor and benzophenone-2 were detected, as well as breakdown products of oxybenzone, including benzophenone-1, 2,2'-dihydroxy-4-methoxybenzophenone, and 4-hydroxybenzophenone. Dioxybenzone (DHMB) presented the highest concentration in water (75.4 ng/mL), whereas octocrylene was detected in all water samples. Some of these same target analytes were detected in water samples on coral reefs that are adjacent to the beach showers. Risk assessments for both sand and water samples at a majority of the sampling sites had a Risk Quotient > 1, indicating that these chemicals could pose a serious threat to beach zones and coral reef habitats. There are almost a dozen mitigation options that could be employed to quickly reduce contaminant loads associated with discharges from these beach showers, like those currently being employed (post-study sampling and analysis) in the State of Hawaii, including banning the use of sunscreens using petrochemical-based UV filters or educating tourists before they arrive on the beach.
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•Beach showers are a point-source of contamination to coastal surface waters.•Sunscreen contamination was highest at beaches with the highest visitation rates.•Concentrations of UV sunscreens pose a threat to terrestrial and aquatic receptors.•Apply mitigation options to reduce sunscreen pollution from beach showers.
Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, ...cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community-biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations-to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.
Interleukin (IL)-15 is a multifunctional cytokine that shares many biological activities with IL-2. This functional overlap, as well as receptor binding subunits shared by IL-15 and IL-2, suggests ...tertiary structural similarities between these two cytokines. In this study, recombinant human IL-15 was PEGylated via lysine-specific conjugation chemistry in order to extend the circulation half-life of this cytokine. Although PEGylation did extend the β-elimination circulation half-life of IL-15 by greater than 50-fold, the biological activity of polyethylene glycol (PEG)-IL-15 was significantly altered. Specifically, PEG-IL-15 lost its ability to stimulate the proliferation of CTLL but took on the properties of a specific IL-15 antagonist in vitro. In comparing sequence alignments and molecular models for IL-2 and IL-15, it was noted that lysine residues resided in regions of IL-15 that may have selectively disrupted receptor subunit binding. We hypothesized that PEGylation of IL-15 interferes with β but not α receptor subunit binding, resulting in the IL-15 antagonist activity observed in vitro. The validity of this hypothesis was tested by engineering site-specific mutants of human IL-15 as suggested by the IL-15 model (IL-15D8S and IL-15Q108S block β and γ receptor subunit binding, respectively). As with PEG-IL-15, these mutants were unable to stimulate CTLL proliferation but were able to specifically inhibit the proliferation of CTLL in response to unmodified IL-15. These results supported our model of IL-15 and confirmed that interference of β receptor subunit binding by adjacent PEGylation could be responsible for the altered biological activity observed for PEG-IL-15.
Knowledge of the past behavior of Antarctic polynyas such as the Ross and Weddell Seas contributes to the understanding of biological productivity, sea ice production, katabatic and Southern ...Hemisphere Westerly (SHW) wind strength, Antarctic bottom water (ABW) formation, and marine CO2 sequestration. Previous studies link barium (Ba) marine sedimentation to polynya primary productivity (Bonn et al., 1998; McManus et al., 2002; Pirrung et al., 2008), polynya area to katabatic wind strength and proximal cyclones (Bromwich et al., 1998; Drucker et al., 2011), and highlight the influence of Ross Ice Shelf calving event effects on the Ross Sea Polynya (RSP) (Rhodes et al., 2009). Here we use the RICE ice core, located just 120 km from the Ross Ice Shelf front to capture 1150 years of RSP behavior. We link atmospheric Ba fluctuations to Ba marine sedimentation in the summer Ross Sea Polynya, creating the first deep ice core based RSP proxy. RSP area is currently the smallest ever observed over our 1150-year record, and varied throughout the Little Ice Age with fluctuations in Amundsen Sea Low (ASL) strength related with Ross Sea cyclones. Past RSP reconstructions allow us to predict future responses of RSP area to future climate change, which is of special interest considering the recent disappearance of the Weddell Sea Polynya in response to anthropogenic forcing (de Lavergne et al., 2014).
We investigate anew the distribution of absolute carbon abundance, \(A\)(C) \(= \log\,\epsilon \)(C), for carbon-enhanced metal-poor (CEMP) stars in the halo of the Milky Way, based on ...high-resolution spectroscopic data for a total sample of 305 CEMP stars. The sample includes 147 CEMP-\(s\) (and CEMP-r/s) stars, 127 CEMP-no stars, and 31 CEMP stars that are unclassified, based on the currently employed Ba/Fe criterion. We confirm previous claims that the distribution of \(A\)(C) for CEMP stars is (at least) bimodal, with newly determined peaks centered on \(A\)(C)\(=7.96\) (the high-C region) and \(A\)(C)\( =6.28\) (the low-C region). A very high fraction of CEMP-\(s\) (and CEMP-r/s) stars belong to the high-C region, while the great majority of CEMP-no stars reside in the low-C region. However, there exists complexity in the morphology of the \(A\)(C)-Fe/H space for the CEMP-no stars, a first indication that more than one class of first-generation stellar progenitors may be required to account for their observed abundances. The two groups of CEMP-no stars we identify exhibit clearly different locations in the \(A\)(Na)-\(A\)(C) and \(A\)(Mg)-\(A\)(C) spaces, also suggesting multiple progenitors. The clear distinction in \(A\)(C) between the CEMP-\(s\) (and CEMP-\(r/s\)) stars and the CEMP-no stars appears to be \(as\ successful\), and \(likely\ more\ astrophysically\ fundamental\), for the separation of these sub-classes as the previously recommended criterion based on Ba/Fe (and Ba/Eu) abundance ratios. This result opens the window for its application to present and future large-scale low- and medium-resolution spectroscopic surveys.
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