Intermediate or Intensive Care Unit Admission across Race and Ethnicity.

OBJECTIVES: The aim of this study was to assess the association between race and ethnicity and admission to intermediate (IMCUs) or intensive care units (ICUs) among hospitalized patients. METHODS: Using Florida hospital discharge data from the Agency for Healthcare Research and Quality-sponsored State Inpatient Database in 2017, we assessed the relationship between race (White, Black, Other) and Hispanic ethnicity and IMCU or ICU admission. Demographic covariates included age, sex, quartile of household income for patient ZIP code, insurance status, and patient residence. An adjusted model assessed the association between race and ethnicity and IMCU or ICU admission using log binomial regression with generalized estimating equations after controlling for demographic characteristics and the Elixhauser Comorbidity Index. RESULTS: After controlling for demographics and comorbidities, the prevalence of IMCU or ICU admission was higher among non-Hispanic Blacks (adjusted prevalence ratio [aPR] 1.04; 95% confidence interval [CI] 1.02-1.05) and non-Hispanic patients of other races (aPR 1.03; 95% CI 1.01-1.04) compared with non-Hispanic Whites. The prevalence of IMCU or ICU use was lower among Hispanic Whites (aPR 0.98; 95% CI 0.86-1.00) and Hispanics of other races (aPR 0.96; 95% CI 0.95-0.98) compared with non-Hispanic Whites after controlling for other demographic characteristics and comorbidities. CONCLUSIONS: Among hospitalized patients, racial minorities are slightly more likely to use higher levels of care, whereas Hispanic patients are generally slightly less likely than non-Hispanic White patients to use higher levels of care. Further evaluation is needed to identify reasons for disparate IMCU or ICU admission.

Loss of Smell and Taste Among Healthcare Personnel Screened for Coronavirus 2019.

Among 283 symptomatic healthcare personnel (HCP) tested for SARS-CoV-2, 51 (18%) were positive. Among those 51 HCP, self reported loss of smell and taste were present in 51% and 52.9%, respectively, with either present in 60.8%. These symptoms had high specificity (93% each, 96% for either) for a positive SARS-CoV-2 test.

The gut microbiome's role in the development, maintenance, and outcomes of sepsis.

The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.

Plasma 25-Hydroxyvitamin D and the Longitudinal Risk of Sepsis in the REGARDS Cohort.

BACKGROUND: Low baseline plasma 25-hydroxyvitamin D (25(OH)D) is associated with increased risk of acute respiratory infections, but its association with long-term risk of sepsis remains unclear. METHODS: We performed a case-cohort analysis of participants selected from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US cohort of 30239 adults aged ≥45 years. We measured baseline plasma 25(OH)D in 711 sepsis cases and in 992 participants randomly selected from the REGARDS cohort. We captured sepsis events by screening records with International Classification of Disease methods and then adjudicating clinical charts for significant, suspected infection and severe inflammatory response syndrome criteria on presentation. RESULTS: In the study sample, the median age of participants was 65.0 years, 41% self-identified as black, and 45% were male. Mean plasma 25(OH)D concentration was 25.8 ng/mL; for 31% of participants, it was <20 ng/mL. The adjusted risk of community-acquired sepsis was higher for each lower category of baseline 25(OH)D. Specifically, in a Cox proportional hazards model adjusting for multiple potential confounders, when compared to a baseline 25(OH)D >33.6 ng/mL, lower 25(OH)D groups were associated with higher hazards of sepsis (16.5-22.4 ng/mL; hazard ratio [HR]; 3.21; 95% confidence interval [CI], 1.98 to 5.21 and <16.5 ng/mL; HR, 6.81, 95% CI, 3.95 to 11.73). Results did not materially differ in analyses stratified by race or age. CONCLUSIONS: In the REGARDS cohort of community-dwelling US adults, low plasma 25(OH)D measured at a time of relative health was independently associated with increased risk of sepsis.

Definitions, Epidemiology, Clinical Risk Factors, and Health Disparities in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a syndrome of inflammatory lung injury currently defined as the rapid onset of hypoxemia and radiographic opacities from a recent direct or indirect insult that is not explained by other causes. While the diagnostic criteria used to define ARDS are helpful in the clinical setting, they are not entirely specific for the characteristic pathophysiology of diffuse alveolar lung damage. This case definition introduces challenges to the reliable and accurate epidemiologic study of the condition. Within these limitations, ARDS appears to be a condition that is relatively rare within the general population but common within the context of the intensive care unit. Furthermore, the frequency and outcomes of ARDS seem to vary between populations, with no clearly discernible temporal trends in incidence or case fatality that are uniform across studies.

Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

The Association Between Acute Respiratory Distress Syndrome Hospital Case Volume and Mortality in a U.S. Cohort, 2002-2011.

OBJECTIVES: This study examines the relationships between hospitals' annual acute respiratory distress syndrome case volume with hospitals' acute respiratory distress syndrome case fatality rates and individuals' odds of acute respiratory distress syndrome hospital mortality. DESIGN: Retrospective cohort study. SETTING: The U.S. Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, 2002-2011. PATIENTS: Acute respiratory distress syndrome discharges defined by the presence of an acute respiratory distress syndrome International Classification of Diseases, 9th revision, Clinical Modification diagnosis code (518.82 or 518.5) and a mechanical ventilation procedure code (96.70, 96.71 or 96.72) on the discharge diagnosis and procedure lists. If the procedure code 96.71 was on the discharge record (mechanical ventilation < 96 hr duration), the patient also needed to be classified as deceased. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 2,686 hospitals and 117,204 cases of acute respiratory distress syndrome. Average annual hospital acute respiratory distress syndrome in-hospital mortality was 47%. Acute respiratory distress syndrome case volume was categorized as low (1-9), medium (10-49), and high (50-423 cases per year). In a hospital-level Poisson regression adjusting for hospital characteristics, when compared with low-volume acute respiratory distress syndrome hospitals, high- and medium-volume acute respiratory distress syndrome hospitals had lower annual acute respiratory distress syndrome case fatality (rate ratio, 0.75; 99% CI, 0.71-0.79 and rate ratio, 0.86; 99% CI, 0.82-0.90, respectively; p ≤ 0.001 for both). In an individual-level, multivariable model adjusting for hospital and individual characteristics, high and medium acute respiratory distress syndrome volume hospitals were associated with lower odds of acute respiratory distress syndrome mortality compared with low-volume hospitals (odds ratio, 0.85 [99% CI, 0.74-0.99]; p = 0.006 and odds ratio, 0.89 [99% CI 0.79-1.00]; p = 0.01, respectively). CONCLUSIONS: In this cohort, at both an individual- and hospital-level, higher acute respiratory distress syndrome hospital case volume is associated with lower acute respiratory distress syndrome hospital mortality.

Sepsis is a preventable public health problem.

There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.

Serial Daily Organ Failure Assessment Beyond ICU Day 5 Does Not Independently Add Precision to ICU Risk-of-Death Prediction.

OBJECTIVES: To identify circumstances in which repeated measures of organ failure would improve mortality prediction in ICU patients. DESIGN: Retrospective cohort study, with external validation in a deidentified ICU database. SETTING: Eleven ICUs in three university hospitals within an academic healthcare system in 2014. PATIENTS: Adults (18 yr old or older) who satisfied the following criteria: 1) two of four systemic inflammatory response syndrome criteria plus an ordered blood culture, all within 24 hours of hospital admission; and 2) ICU admission for at least 2 calendar days, within 72 hours of emergency department presentation. INTERVENTION: NoneMEASUREMENTS AND MAIN RESULTS:: Data were collected until death, ICU discharge, or the seventh ICU day, whichever came first. The highest Sequential Organ Failure Assessment score from the ICU admission day (ICU day 1) was included in a multivariable model controlling for other covariates. The worst Sequential Organ Failure Assessment scores from the first 7 days after ICU admission were incrementally added and retained if they obtained statistical significance (p < 0.05). The cohort was divided into seven subcohorts to facilitate statistical comparison using the integrated discriminatory index. Of the 1,290 derivation cohort patients, 83 patients (6.4%) died in the ICU, compared with 949 of the 8,441 patients (11.2%) in the validation cohort. Incremental addition of Sequential Organ Failure Assessment data up to ICU day 5 improved the integrated discriminatory index in the validation cohort. Adding ICU day 6 or 7 Sequential Organ Failure Assessment data did not further improve model performance. CONCLUSIONS: Serial organ failure data improve prediction of ICU mortality, but a point exists after which further data no longer improve ICU mortality prediction of early sepsis.

Associations Between Vitamin D Level and Hospitalizations With and Without an Infection in a National Cohort of Medicare Beneficiaries.

Research has implicated low 25-hydroxyvitamin D (25(OH)D) level as a risk factor for infection; however, results have not been consistent. To further determine the nature of this relationship, we conducted a cohort study using Medicare beneficiaries participating in the 2001-2002 and 2003-2004 cycles of the National Health and Nutrition Examination Survey with data individually linked to hospital records from the Centers for Medicare and Medicaid Services. The primary exposure was a 25(OH)D level of <15 ng/mL versus ≥15 ng/mL. The outcomes were a hospitalization with or without an infection within 1 year of participation in the National Health and Nutrition Examination Survey, as determined from the final hospital discharge codes (International Classification of Diseases, Ninth Revision, Clinical Modification). Of 1,713 individuals, 348 had a baseline serum 25(OH)D level of <15 ng/mL, 77 experienced a hospitalization with an infection, and 287 experienced a hospitalization without an infection. In multivariable analyses, a serum 25(OH)D level of <15 ng/mL was associated with a higher risk of hospitalization with an infection (risk ratio = 2.8, 95% confidence interval: 1.3, 5.9, P < 0.01) but not of hospitalization without an infection (risk ratio = 1.4, 95% confidence interval: 0.9, 2.1, P = 0.1). In this study, we found an association between a serum 25(OH)D concentration of <15 ng/mL and a higher subsequent risk for hospitalization with an infection among Medicare beneficiaries.

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Respiratory Infections.

Pneumonia is one of the most common reasons for health care utilization in the United States. It can be caused by many different pathogens, but rarely is it able to be identified in specific cases. This has led most racial disparities research to focus on community acquired pneumonia and microbes of public health concern such as influenza, tuberculosis, and COVID-19. Differences have been shown to exist from prevention with vaccines to management and outcomes. COVID-19 has led to a significant increase in the awareness of this topic.

U.S. Adult Critical Care Beds Per Capita: A 2021 County-Level Cross-Sectional Study.

Per capita geographic distribution of adult critical care beds can be utilized for healthcare resources assessments. OBJECTIVES: Describe the per capita distribution of staffed adult critical care beds across the United States. DESIGN SETTING AND PARTICIPANTS: Cross-sectional epidemiologic assessment of November 2021 hospital data from the Department of Health and Human Services' Protect Public Data Hub. MAIN OUTCOMES AND MEASURES: Staffed adult critical care beds per adult population. RESULTS: The percent of hospitals reporting was high and varied by state/territory (median, 98.6% of states' hospitals reporting; interquartile range [IQR], 97.8-100%). There was a total of 4,846 adult hospitals accounting for 79,876 adult critical care beds in the United States and its territories. Crudely aggregated at the national-level, this calculated to 0.31 adult critical care beds per 1,000 adults. The median crude per capita density of adult critical care beds per 1,000 adults across U.S. counties was 0.00 per 1,000 adults (county, IQR 0.00-0.25; range, 0.00-8.65). Spatially smoothed county-level estimates were obtained using Empirical Bayes and Spatial Empirical Bayes approaches, resulting in an estimated 0.18 adult critical care beds per 1,000 adults (range from both methodological estimates, 0.00-8.20). When compared to counties in the lower quartile of adult critical care bed density, counties in the upper quartile had higher average adult population counts (mean 159,000 vs 32,000 adults per county) and a choropleth map demonstrated high densities of beds in urban centers with low density across rural areas. CONCLUSIONS AND RELEVANCE: Among U.S. counties, the density of critical care beds per capita was not uniformly distributed, with high densities concentrated in highly populated urban centers and relative scarcity in rural areas. As it is unknown what defines deficiency and surplus in terms of outcomes and costs, this descriptive report serves as an additional methodological benchmark for hypothesis-driven research in this area.

Vitamin D in sepsis: from basic science to clinical impact.

The growing basic and clinical investigations into the extraskeletal effects of vitamin D have revealed roles in the functioning of the immune system, generating interesting questions about this nutrient's connections to sepsis. This article briefly reviews the current science of the function of vitamin D in the immune system as well as the emerging clinical literature regarding its associations with respiratory infections, sepsis, and critical illness. Finally, we offer views on the potential future directions for research in the field by outlining potential relevant scenarios and outcomes.

Evidence for an Inherited Contribution to Sepsis Susceptibility Among a Cohort of U.S. Veterans.

Analyze a unique clinical and genealogical resource for evidence of familial clustering of sepsis to test for an inherited contribution to sepsis predisposition. DESIGN: Observational study. SETTING: Veteran's Health Affairs (VHA) Genealogy/Phenotype resource, a U.S. genealogy database with veterans individually linked to VHA electronic health records. PATIENTS: Sepsis was identified using International Classification of Disease, 9th Edition and 10th Edition codes. There were two comparison groups: one composed of the all veterans with linked data and deep genealogy and the other included 1,000 sets of controls, each set randomly sampled from the entire cohort after matching on sex and 10-year birth year range on a 1:1 ratio with cases. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 4,666 cases of sepsis from 2001 to 2018, of which 96% were male and 80% greater than or equal to 65 years old. Utilizing the Genealogical Index of Familiality, there was a significant excess of pairwise relatedness among sepsis cases over that in the control sets sampled from VHA population (p = 0.03). The relative risk (RR) of sepsis among identified relatives compared with the larger linked VHA cohort demonstrated an excess of sepsis cases in the first-degree (RR, 1.39; 95% CI, 1.03-1.92; p = 0.05) and second-degree (RR, 1.50; 95% CI, 1.07-2.17; p = 0.04) relatives that were not demonstrated in higher degree relatives. The sepsis cases clustered into 1,876 pedigrees of which 628 had a significant excess of sepsis cases among the descendants (p < 0.05). CONCLUSIONS: The data from this cohort of nearly all male U.S. veterans demonstrate evidence for contribution of an inherited predisposition to sepsis and the existence of pedigrees with a significant excess of diagnoses that provide a valuable resource for identification of the predisposition genes and variants responsible. This complements studies on individual genetic variants toward estimating the heritability patterns and clinical relevance of genetic sepsis predisposition.