Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons.

OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥ 2.0 mg/dL, decrease in platelets to < 100 cells/µL, or lactate ≥ 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals' claims data was low and variable: median 30% (range, 5-54%) for sepsis, 66% (range, 26-84%) for acute kidney injury, 39% (range, 16-60%) for thrombocytopenia, 36% (range, 29-44%) for hepatic injury, and 66% (range, 29-84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data. CONCLUSIONS: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals' sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons.

Deep RNA sequencing of intensive care unit patients with COVID-19.

COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.

Abdominal Pain Due to Renal Infarction: An Unexpected Presentation of COVID-19.

Although respiratory symptoms dominate the clinical presentation of COVID-19, atypical, misleading non-pulmonary complaints can occur. Here we present a case of an otherwise healthy 28-year-old cisgender woman whose initial presentation of COVID-19 was unexplained acute abdominal pain, which was later found to be due to renal infarction. She was treated with anti-coagulation and was discharged after a short hospital stay. This case demonstrates the heterogeneous presentations that are associated with COVID-19. Medical providers must be aware that this virus may mimic a diverse array of disorders, even in the absence of respiratory symptoms.

Deep RNA Sequencing of Intensive Care Unit Patients with COVID-19.

PURPOSE: COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. METHODS: Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (>100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. RESULTS: We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. CONCLUSIONS: Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies. TAKE HOME MESSAGE: Deep RNA sequencing provides a novel diagnostic tool for critically ill patients. Among ICU patients with COVID-19, RNA sequencings can identify gene expression, pathogens (including SARS-CoV-2), and can predict mortality. TWEET: Deep RNA sequencing is a novel technology that can assist in the care of critically ill COVID-19 patients & can be applied to other disease.

The impact of measurement changes on evaluating hospital performance: The case of catheter-associated urinary tract infections.

Catheter-associated urinary tract infections in 592 hospitals immediately declined after federal value-based incentive program implementation, but this was fully attributable to a concurrent surveillance case definition revision. Post revision, more hospitals had favorable standardized infection ratios, likely leading to artificial inflation of their performance scores unrelated to changes in patient safety.

Comparison of hospital surgical site infection rates and rankings using claims versus National Healthcare Safety Network surveillance data.

National policies target healthcare-associated infections using medical claims and National Healthcare Safety Network surveillance data. We found low concordance between the 2 data sources in rates and rankings for surgical site infection following colon surgery in 155 hospitals, underscoring the limitations in evaluating hospital quality by claims data.

Impact of the 2012 Medicaid Health Care-Acquired Conditions Policy on Catheter-Associated Urinary Tract Infection and Vascular Catheter-Associated Infection Billing Rates.

In July 2012, the Centers for Medicare & Medicaid Services ceased hospital Medicaid reimbursements for certain health care-acquired conditions. Using billing data from 2008-2014, we found no impact of this policy on rates of 2 targeted conditions, vascular catheter-associated infections and catheter-associated urinary tract infections, among Medicaid or non-Medicaid patients.

The Impact of the Medicaid Healthcare-Associated Condition Program on Mediastinitis Following Coronary Artery Bypass Graft.

OBJECTIVEIn 2012, the Centers for Medicare and Medicaid Services expanded a 2008 program that eliminated additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) to include Medicaid. We aimed to evaluate the impact of this Medicaid program on mediastinitis rates reported by the National Healthcare Safety Network (NHSN) compared with the rates of a condition not targeted by the program, deep-space surgical site infection (SSI) after knee replacement.DESIGNInterrupted time series with comparison group.METHODSWe included surveillance data from nonfederal acute-care hospitals participating in the NHSN and reporting CABG or knee replacement outcomes from January 2009 through June 2017. We examined the Medicaid program's impact on NHSN-reported infection rates, adjusting for secular trends. The data analysis used generalized estimating equations with robust sandwich variance estimators.RESULTSDuring the study period, 196 study hospitals reported 273,984 CABGs to the NHSN, resulting in 970 mediastinitis cases (0.35%), and 294 hospitals reported 555,395 knee replacements, with 1,751 resultant deep-space SSIs (0.32%). There was no significant change in incidence of either condition during the study. Mediastinitis models showed no effect of the 2012 Medicaid program on either secular trend during the postprogram versus preprogram periods (P=.70) or an immediate program effect (P=.83). Results were similar in sensitivity analyses when adjusting for hospital characteristics, restricting to hospitals with consistent NHSN reporting or incorporating a program implementation roll-in period. Knee replacement models also showed no program effect.CONCLUSIONSThe 2012 Medicaid program to eliminate additional payments for mediastinitis following CABG had no impact on reported mediastinitis rates.Infect Control Hosp Epidemiol 2018;39:694-700.

Analysis of Septin Reorganization at Cytokinesis Using Polarized Fluorescence Microscopy.

Septins are conserved filament-forming proteins that act in diverse cellular processes. They closely associate with membranes and, in some systems, components of the cytoskeleton. It is not well understood how filaments assemble into higher-order structures in vivo or how they are remodeled throughout the cell cycle. In the budding yeast S. cerevisiae, septins are found through most of the cell cycle in an hourglass organization at the mother-bud neck until cytokinesis when the collar splits into two rings that disassemble prior to the next cell cycle. Experiments using polarized fluorescence microscopy have suggested that septins are arranged in ordered, paired filaments in the hourglass and undergo a coordinated 90° reorientation during splitting at cytokinesis. This apparent reorganization could be due to two orthogonal populations of filaments disassembling and reassembling or being preferentially retained at cytokinesis. In support of this idea, we report a decrease in septin concentration at the mother-bud neck during cytokinesis consistent with other reports and the timing of the decrease depends on known septin regulators including the Gin4 kinase. We took a candidate-based approach to examine what factors control reorientation during splitting and used polarized fluorescence microscopy to screen mutant yeast strains deficient in septin interacting proteins. Using this method, we have linked known septin regulators to different aspects of the assembly, stability, and reorganization of septin assemblies. The data support that ring splitting requires Gin4 activity and an anillin-like protein Bud4, and normal accumulation of septins at the ring requires phosphorylation of Shs1. We found distinct regulatory requirements for septin organization in the hourglass compared to split rings. We propose that septin subpopulations can vary in their localization and assembly/disassembly behavior in a cell-cycle dependent manner at cytokinesis.

Micron-scale plasma membrane curvature is recognized by the septin cytoskeleton.

Cells change shape in response to diverse environmental and developmental conditions, creating topologies with micron-scale features. Although individual proteins can sense nanometer-scale membrane curvature, it is unclear if a cell could also use nanometer-scale components to sense micron-scale contours, such as the cytokinetic furrow and base of neuronal branches. Septins are filament-forming proteins that serve as signaling platforms and are frequently associated with areas of the plasma membrane where there is micron-scale curvature, including the cytokinetic furrow and the base of cell protrusions. We report here that fungal and human septins are able to distinguish between different degrees of micron-scale curvature in cells. By preparing supported lipid bilayers on beads of different curvature, we reconstitute and measure the intrinsic septin curvature preference. We conclude that micron-scale curvature recognition is a fundamental property of the septin cytoskeleton that provides the cell with a mechanism to know its local shape.