Sepsis Among Medicare Beneficiaries: 4. Precoronavirus Disease 2019 Update January 2012-February 2020.

OBJECTIVES: To provide updated information on the burdens of sepsis during acute inpatient admissions for Medicare beneficiaries. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare and Medicaid Services DataLink Project. SETTING: All U.S. acute-care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). PATIENTS: All Medicare beneficiaries, January 2012-February 2020, with an explicit sepsis diagnostic code assigned during an inpatient admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The count of Medicare Part A/B (fee-for-service) plus Medicare Advantage inpatient sepsis admissions rose from 981,027 (CY2012) to 1,700,433 (CY 2019). The proportion of total admissions with sepsis in the Medicare Advantage population rose from 21.43% to 35.39%, reflecting the increasing beneficiary proportion enrolled in Medicare Advantage. In CY2019, 6-month mortality rates in Medicare fee-for-service beneficiaries for sepsis continued to decline, but remained high: 59.9% for septic shock, 35.5% for severe sepsis, 30.8% for sepsis attributed to a specific organism, and 26.5% for unspecified sepsis. Total fee-for-service-only inpatient hospital costs rose from $17.79B (CY2012) to $22.98B (CY2019). We estimated that the aggregate cost of sepsis hospital care for the entire U.S. population was at least $57.47B in 2019. Inclusion of 14 months' (January 2019-February 2020) newer data exposed new trends: the cost per patient, number of admissions, and fraction of patients with sepsis labeled as present on admission inflected around November 2015, coincident with the change to International Classification of Diseases, 10th Edition, and introduction of the Severe Sepsis and Septic Shock Management Bundle (SEP-1) metric. CONCLUSIONS: Sepsis among Medicare beneficiaries precoronavirus disease 2019 imposed immense burdens upon patients, their families, and the taxpayers.

A framework for future national pediatric pandemic respiratory disease severity triage: The HHS pediatric COVID-19 data challenge.

Introduction: With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist. Methods: HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions? Results: This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected. Conclusion: This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.

Tailoring silver nanodots for intracellular staining.

Through tailored oligonucleotide scaffolds, Ag nanocluster syntheses have yielded thermally and cell-culture medium stable silver cluster-based emitters. Optimizing ssDNA stability has enabled creation of highly concentrated and spectrally pure nanocluster emitters with strong intracellular emission. Both fixed and live-cell staining become possible, and intracellular delivery is demonstrated both through conjugation to cell-penetrating peptides and via microinjection.

Seasonal influenza vaccination is associated with reduced risk of death among Medicare beneficiaries☆.

BACKGROUND: Influenza causes substantial mortality, especially among older persons. Influenza vaccines are rarely more than 50% effective and rarely reach more than half of the US Medicare population, which is primarily an aged population. We wished to estimate the association between vaccination and mortality reduction. METHOD: We used the US Center for Medicare and Medicaid Services (CMS) DataLink Project to determine vaccination status and timing during the 2017-2018 influenza season for more than 26 million Medicare enrollees. Patient-level demographic, health, co-morbidity, hospitalization, vaccination, and healthcare utilization claims data were supplied as covariates to general linear models in order to isolate and estimate the association between participation in the vaccination program and relative risk of death. FINDINGS: The 2017-2018 seasonal influenza vaccine reduced (Relative Risk Ratio [RRR] 0.936 [95% CI = 0.918-0.954]) the risk of all-cause death among beneficiaries following a hospitalization for sepsis and moreover the risk of death without a prior hospitalization during the 2.5-month outcome window (RRR 0.870 [95% CI = 0.853-0.887]). We estimate the number needed to vaccinate (NNV) to prevent a death in the ten-week outcome window is between 1,515 beneficiaries (95% CI = 1,351-1,754; derived from the average treatment effect of augmented inverse probability weighting) and 1,960 beneficiaries (95% CI = 1,695-2,381; derived from the average marginal effect of logistic regression). Among beneficiaries requiring hospitalization, the greatest death risk reduction accrued to those 85 + years of age who were hospitalized with sepsis, RRR 0.92 [95% CI = 0.89-0.95]. No apparent benefit was realized by beneficiaries who required custodial (nursing home) care. INTERPRETATION: Seasonal influenza immunization is associated with relative reduction of death risk among non-institutionalized Medicare beneficiaries. FUNDING: All authors are full-time or contractual employees of the United States Federal Government, Department of Health and Human Services, the funding agency.

Water-soluble Ag nanoclusters exhibit strong two-photon-induced fluorescence.

Water-soluble ssDNA-encapsulated Ag clusters exhibit large two-photon cross sections reaching 50 000 GM, with high quantum yields in the red and near-IR. Three distinct, spectrally pure, several atom clusters emitting at 660, 680, or 710 nm have been created with two-photon cross sections rivaling those of much larger water-soluble semiconductor quantum dots. Their stability, biocompatibility, and small size offer the promise of nontoxic, sensitive high-resolution biological imaging.

Electron transfer-induced blinking in Ag nanodot fluorescence.

Various single-standed DNA-encapsulated Ag nanoclusters (nanodots) exhibit strong, discrete fluorescence with solvent polarity-dependent absorption and emission throughout the visible and near-IR. All species examined, regardless of their excitation and emission energies, show similar µs single-molecule blinking dynamics and near IR transient absorptions. The polarity dependence, µsec blinking, and indistinguishable µsec-decaying transient absorption spectra for multiple nanodots suggest a common charge transfer-based mechanism that gives rise to nanodot fluorescence intermittency. Photoinduced charge transfer that is common to all nanodot emitters is proposed to occur from the Ag cluster into the nearby DNA bases to yield a long-lived charge-separated trap state that results in blinking on the single molecule level.

Revisiting the hexane-water interface via molecular dynamics simulations using nonadditive alkane-water potentials.

We present results addressing properties of a polarizable force field for hexane based on the fluctuating charge (FQ) formalism and developed in conjunction with the Chemistry at Harvard Molecular Mechanics (CHARMM) potential function. Properties of bulk neat hexane, its liquid-vapor interface, and its interface with a polarizable water model (TIP4P-FQ) are discussed. The FQ model is compared to a recently modified alkane model, C27r, also based on the CHARMM potential energy function. With respect to bulk properties, both models predict bulk density within 1%; the FQ model predicts the liquid vaporization enthalpy within 2%, while the C27r force field underestimates the property by roughly 20% (and in this sense reflects the quality of the C27r force field across the spectrum of linear and branched alkanes). The FQ hexane model realistically captures the dielectric properties of the bulk in terms of a dielectric constant of 1.94, in excellent agreement with experimental values in the range of 1.9-2.02. This behavior is also in conformity with a recent polarizable alkane model based on Drude oscillators. Furthermore, the bulk dielectric is essentially captured in the infinite frequency, or optical, dielectric contribution. The FQ model is in this respect a more realistic force field for modeling lipid bilayer interiors for which most current state-of-the-art force fields do not accurately capture the dielectric environment. The molecular polarizability of the FQ model is 11.79 A3, in good agreement with the range of experimental and ab initio values. In contrast to FQ models of polar solvents such as alcohols and water, there was no need to scale gas-phase polarizabilities in order to avoid polarization catastrophes in the pure bulk. In terms of the liquid-vapor and liquid-liquid interfaces, the FQ model displays a rich orientational structure of alkane and water in the respective interfacial systems, in general conforming with earlier simulation studies of such interfaces. The FQ force field shows a marked deviation in the interfacial dipole potentials computed from the charge densities averaged over simulation trajectories. At the liquid-vapor interface, the FQ model predicts a potential drop of -178.71 mV in contrast to the C27r estimate of -433.80 mV. For the hexane-water interface, the FQ force field predicts a dipole potential drop of -379.40 mV in contrast to the C27r value of -105.42 mV. Although the surface dipole potential predicted by the FQ model is roughly 3.5 times that predicted by the C27r potential, it is consistent with reported experimental potentials across solvated lipid bilayers in the range of 400-600 mV.

Nanoparticle-free single molecule anti-stokes Raman spectroscopy.

In the absence of large, plasmon-supporting nanoparticles, biocompatible dendrimer- and peptide-encapsulated few-atom Ag nanoclusters produce scaffold-specific single molecule (SM) Stokes and anti-Stokes Raman scattering. The strong SM vibrational signatures are enhanced by the Agn transitions in nanoparticle-free samples and cannot arise from plasmon enhancement. Characteristic SM-Raman intermittency is observed, with antibunching of the underlying Agn emission directly confirming the SM nature of the emissive species.