This study describes reasons for readmission, use of ICU interventions during readmission, and proportions of death after initial hospital discharge of COVID-19 patients from US Veterans Affairs (VA) ...hospitals in March-June 2020.
IMPORTANCE: The Epic Sepsis Model (ESM), a proprietary sepsis prediction model, is implemented at hundreds of US hospitals. The ESM’s ability to identify patients with sepsis has not been adequately ...evaluated despite widespread use. OBJECTIVE: To externally validate the ESM in the prediction of sepsis and evaluate its potential clinical value compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among 27 697 patients aged 18 years or older admitted to Michigan Medicine, the academic health system of the University of Michigan, Ann Arbor, with 38 455 hospitalizations between December 6, 2018, and October 20, 2019. EXPOSURE: The ESM score, calculated every 15 minutes. MAIN OUTCOMES AND MEASURES: Sepsis, as defined by a composite of (1) the Centers for Disease Control and Prevention surveillance criteria and (2) International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes accompanied by 2 systemic inflammatory response syndrome criteria and 1 organ dysfunction criterion within 6 hours of one another. Model discrimination was assessed using the area under the receiver operating characteristic curve at the hospitalization level and with prediction horizons of 4, 8, 12, and 24 hours. Model calibration was evaluated with calibration plots. The potential clinical benefit associated with the ESM was assessed by evaluating the added benefit of the ESM score compared with contemporary clinical practice (based on timely administration of antibiotics). Alert fatigue was evaluated by comparing the clinical value of different alerting strategies. RESULTS: We identified 27 697 patients who had 38 455 hospitalizations (21 904 women 57%; median age, 56 years interquartile range, 35-69 years) meeting inclusion criteria, of whom sepsis occurred in 2552 (7%). The ESM had a hospitalization-level area under the receiver operating characteristic curve of 0.63 (95% CI, 0.62-0.64). The ESM identified 183 of 2552 patients with sepsis (7%) who did not receive timely administration of antibiotics, highlighting the low sensitivity of the ESM in comparison with contemporary clinical practice. The ESM also did not identify 1709 patients with sepsis (67%) despite generating alerts for an ESM score of 6 or higher for 6971 of all 38 455 hospitalized patients (18%), thus creating a large burden of alert fatigue. CONCLUSIONS AND RELEVANCE: This external validation cohort study suggests that the ESM has poor discrimination and calibration in predicting the onset of sepsis. The widespread adoption of the ESM despite its poor performance raises fundamental concerns about sepsis management on a national level.
OBJECTIVE:Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved ...markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non–cancer-related sepsis.
DESIGN:Observational cohort.
SETTING:National Readmissions Database (2013–2014), containing all-payer claims for 49% of U.S. population.
PATIENTS:A total of 1,104,363 sepsis hospitalizations.
INTERVENTIONS:We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non–cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non–cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses.
MEASUREMENTS AND MAIN RESULTS:There were 27,481,517 hospitalizations in National Readmissions Database 2013–2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non–cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non–cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non–cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non–cancer-related sepsis (p < 0.001).
CONCLUSIONS:In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis.
Summary Background The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) present clinical criteria for the classification of patients with sepsis. We investigated ...incidence and long-term outcomes of patients diagnosed with these classifications, which are currently unknown. Methods We did a retrospective analysis using data from 30 239 participants from the USA who were aged at least 45 years and enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Patients were enrolled between Jan 25, 2003, and Oct 30, 2007, and we identified hospital admissions from Feb 5, 2003, to Dec 31, 2012, and applied three classifications: infection and systemic inflammatory response syndrome (SIRS) criteria, elevated sepsis-related organ failure assessment (SOFA) score from Sepsis-3, and elevated quick SOFA (qSOFA) score from Sepsis-3. We estimated incidence during the study period, in-hospital mortality, and 1-year mortality. Findings Of 2593 first infection events, 1526 met SIRS criteria, 1080 met SOFA criteria, and 378 met qSOFA criteria. Incidence was 8·2 events (95% CI 7·8–8·7) per 1000 person-years for SIRS, 5·8 events (5·4–6·1) per 1000 person-years for SOFA, and 2·0 events (1·8–2·2) per 1000 person-years for qSOFA. In-hospital mortality was higher for patients with an elevated qSOFA score (67 23% of 295 patients died) than for those with an elevated SOFA score (125 13% of 960 patients died) or who met SIRS criteria (128 9% of 1392 patients died). Mortality at 1 year after discharge was also highest for patients with an elevated qSOFA score (29·4 deaths 95% CI 22·3–38·7 per 100 person-years) compared with those with an elevated SOFA score (22·6 deaths 19·2–26·6 per 100 person-years) or those who met SIRS criteria (14·7 deaths 12·5–17·2 per 100 person-years). Interpretation SIRS, SOFA, and qSOFA classifications identified different incidences and mortality. Our findings support the use of the SOFA and qSOFA classifications to identify patients with infection who are at elevated risk of poor outcomes. These classifications could be used in future epidemiological assessments and studies of patients with infection. Funding National Institute for Nursing Research, National Center for Research Resources, and National Institute of Neurological Disorders and Stroke.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
OBJECTIVES:The emergency department is an important venue for initial sepsis recognition and care. We sought to determine contemporary estimates of the epidemiology of U.S. emergency department ...visits for sepsis.
DESIGN:Analysis of data from the National Hospital Ambulatory Medical Care Survey.
SETTING:U.S. emergency department visits, 2009–2011.
PATIENTS:Adult (age, ≥ 18 yr) emergency department sepsis patients. We defined serious infection as an emergency department diagnosis of a serious infection or a triage temperature greater than 38°C or less than 36°C. We defined three emergency department sepsis classifications1) original emergency department sepsis—serious infection plus emergency department diagnosis of organ dysfunction, endotracheal intubation, or systolic blood pressure less than or equal to 90 mm Hg or explicit sepsis emergency department diagnoses; 2) quick Sequential Organ Failure Assessment emergency department sepsis—serious infection plus presence of at least two “quick” Sequential Organ Failure Assessment criteria (Glasgow Coma Scale ≤ 14, respiratory rate ≥ 22 breaths/min, or systolic blood pressure ≤ 100 mm Hg); and 3) revised emergency department sepsis—original or quick Sequential Organ Failure Assessment emergency department sepsis.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:We used survey design and weighting variables to produce national estimates of annual adult emergency department visits using updated sepsis classifications. Over 2009–2011, there were 103,257,516 annual adult emergency department visits. The estimated number of emergency department sepsis visits were as follows1) original emergency department sepsis 665,319 (0.64%; 95% CI, 0.57–0.73); 2) quick Sequential Organ Failure Assessment emergency department sepsis 318,832 (0.31%; 95% CI, 0.26–0.37); and 3) revised emergency department sepsis 847,868 (0.82%; 95% CI, 0.74–0.91).
CONCLUSIONS:Sepsis continues to present a major burden to U.S. emergency departments, affecting up to nearly 850,000 emergency department visits annually. Updated sepsis classifications may impact national estimates of emergency department sepsis epidemiology.
OBJECTIVES:Severe sepsis poses a major burden on the U.S. healthcare system. Previous epidemiologic studies have not differentiated community-acquired severe sepsis from healthcare-associated severe ...sepsis or hospital-acquired severe sepsis hospitalizations. We sought to compare and contrast community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis hospitalizations in a national hospital sample.
DESIGN:Retrospective analysis of severe sepsis discharges from University HealthSystem Consortium hospitals in 2012.
SETTING:United States.
PATIENTS:We used the criteria from Angus et al (discharge diagnoses for both a serious infection and organ dysfunction) to identify severe sepsis hospitalizations. We defined healthcare-associated severe sepsis as severe sepsis hospitalizations with an infection present at admission, where the patient was a nursing home resident, was on hemodialysis, or was readmitted within 30 days of a prior hospitalization. We defined community-acquired severe sepsis as all other severe sepsis patients with an infection present at admission. We defined hospital-acquired severe sepsis as severe sepsis patients where the documented infection was not present at admission.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Prevalence of community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis, adjusted hospital mortality, length of hospitalization, length of stay in an ICU, and hospital costs. Among 3,355,753 hospital discharges, there were 307,491 with severe sepsis, including 193,081 (62.8%) community-acquired severe sepsis, 79,581 (25.9%) healthcare-associated severe sepsis, and 34,829 (11.3%) hospital-acquired severe sepsis. Hospital-acquired severe sepsis and healthcare-associated severe sepsis exhibited higher in-hospital mortality than community-acquired severe sepsis (hospital acquired 19.2% vs healthcare associated 12.8% vs community acquired 8.6%). Hospital-acquired severe sepsis had greater resource utilization than both healthcare-associated severe sepsis and community-acquired severe sepsis, with higher median length of hospital stay (hospital acquired 17 d vs healthcare associated 7 d vs community acquired 6 d), median length of ICU stay (hospital acquired 8 d vs healthcare associated 3 d vs community acquired 3 d), and median hospital costs (hospital acquired $38,369 vs healthcare associated $8,796 vs community acquired $7,024).
CONCLUSIONS:In this series, severe sepsis hospitalizations included community-acquired severe sepsis (62.8%), healthcare-associated severe sepsis (25.9%), and hospital-acquired severe sepsis (11.3%) cases. Hospital-acquired severe sepsis was associated with both higher mortality and resource utilization than community-acquired severe sepsis and healthcare-associated severe sepsis.
The parasite Fasciola hepatica infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, ...rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Here, transcriptome and proteome analysis of ex vivo F. hepatica metacercariae and NEJ reveal the rapidity and multitude of metabolic and developmental alterations that take place in order for the parasite to establish infection. We found that metacercariae despite being encased in a cyst are metabolically active, and primed for infection. Following excystment, NEJ expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new and increasingly anaerobic environment. Temperature increases induce neoblast proliferation and the remarkable up-regulation of genes associated with growth and development. Cysteine proteases synthesized by gastrodermal cells are secreted to facilitate invasion and tissue degradation, and tegumental transporters, such as aquaporins, are varied to deal with osmotic/salinity changes. Major proteins of the total NEJ secretome include proteases, protease inhibitors and anti-oxidants, and an array of immunomodulators that likely disarm host innate immune effector cells. Thus, the challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion; these changes facilitate parasite growth, development and maturation. Our molecular analysis of the critical processes involved in host invasion has identified key targets for future drug and vaccine strategies directed at preventing parasite infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, ...growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to simultaneously counter infection and repair tissue damage.
Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. Immature liver-stage flukes express ~ 8000 transcripts that are enriched for transcription and translation processes reflective of intensive protein production and signal transduction pathways. Key pathways that regulate neoblast/pluripotent cells, including the PI3K-Akt signalling pathway, are particularly dominant and emphasise the importance of neoblast-like cells for the parasite's rapid development. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite's destructive migration, and digestion of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defence molecules (FhHDM). Combined with published host microarray data, our results suggest that considerable immune cell infiltration and subsequent fibrosis of the liver tissue exacerbates oxidative stress within parenchyma that compels the expression of a range of antioxidant molecules within both host and parasite.
The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and antioxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predicting long-term outcomes in sepsis survivors remains a difficult task. Persistent inflammation post-sepsis is associated with increased risk for rehospitalization and death. As surrogate markers ...of inflammation, complete blood count parameters measured at hospital discharge may have prognostic value for sepsis survivors.
To determine the incremental value of complete blood count parameters over clinical characteristics for predicting 90-day outcomes in sepsis survivors.
Electronic health record data was used to identify sepsis hospitalizations at United States Veterans Affairs hospitals with live discharge and relevant laboratory data (2013 to 2018). We measured the association of eight complete blood count parameters with 90-day outcomes (mortality, rehospitalization, cause-specific rehospitalizations) using multivariable logistic regression models.
We identified 155,988 eligible hospitalizations for sepsis. Anemia (93.6%, N=142,162) and lymphopenia (28.1%, N=29,365) were the most common blood count abnormalities at discharge. In multivariable models, all parameters were associated with the primary outcome of 90-day mortality or rehospitalization and improved model discrimination above clinical characteristics alone (likelihood ratio test, p<0.02 for all). A model including all eight parameters significantly improved discrimination (AUROC, 0.6929 v. 0.6756) and reduced calibration error for the primary outcome. Hemoglobin had the greatest prognostic separation with a 1.5 fold increased incidence of the primary outcome in the lowest quintile (7.2-8.9 g/dL) versus highest quintile (12.70-15.80 g/dL). Hemoglobin and neutrophil lymphocyte ratio provided the most added value in predicting the primary outcome and 90-day mortality alone, respectively. Absolute lymphocyte count added little value in predicting 90-day outcomes.
The incorporation of discharge complete blood count parameters into prognostic scoring systems could improve prediction of 90-day outcomes. Hemoglobin had the greatest prognostic value for the primary composite outcome of 90-day rehospitalization or mortality. Absolute lymphocyte count provided little added value in multivariable model comparisons, including for infection- or sepsis-related rehospitalization.
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