Quick Sepsis-related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit.

RATIONALE: The 2016 definitions of sepsis included the quick Sepsis-related Organ Failure Assessment (qSOFA) score to identify high-risk patients outside the intensive care unit (ICU). OBJECTIVES: We sought to compare qSOFA with other commonly used early warning scores. METHODS: All admitted patients who first met the criteria for suspicion of infection in the emergency department (ED) or hospital wards from November 2008 until January 2016 were included. The qSOFA, Systemic Inflammatory Response Syndrome (SIRS), Modified Early Warning Score (MEWS), and the National Early Warning Score (NEWS) were compared for predicting death and ICU transfer. MEASUREMENTS AND MAIN RESULTS: Of the 30,677 included patients, 1,649 (5.4%) died and 7,385 (24%) experienced the composite outcome (death or ICU transfer). Sixty percent (n = 18,523) first met the suspicion criteria in the ED. Discrimination for in-hospital mortality was highest for NEWS (area under the curve [AUC], 0.77; 95% confidence interval [CI], 0.76-0.79), followed by MEWS (AUC, 0.73; 95% CI, 0.71-0.74), qSOFA (AUC, 0.69; 95% CI, 0.67-0.70), and SIRS (AUC, 0.65; 95% CI, 0.63-0.66) (P < 0.01 for all pairwise comparisons). Using the highest non-ICU score of patients, ≥2 SIRS had a sensitivity of 91% and specificity of 13% for the composite outcome compared with 54% and 67% for qSOFA ≥2, 59% and 70% for MEWS ≥5, and 67% and 66% for NEWS ≥8, respectively. Most patients met ≥2 SIRS criteria 17 hours before the combined outcome compared with 5 hours for ≥2 and 17 hours for ≥1 qSOFA criteria. CONCLUSIONS: Commonly used early warning scores are more accurate than the qSOFA score for predicting death and ICU transfer in non-ICU patients. These results suggest that the qSOFA score should not replace general early warning scores when risk-stratifying patients with suspected infection.

Investigating the Impact of Different Suspicion of Infection Criteria on the Accuracy of Quick Sepsis-Related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores.

OBJECTIVE: Studies in sepsis are limited by heterogeneity regarding what constitutes suspicion of infection. We sought to compare potential suspicion criteria using antibiotic and culture order combinations in terms of patient characteristics and outcomes. We further sought to determine the impact of differing criteria on the accuracy of sepsis screening tools and early warning scores. DESIGN: Observational cohort study. SETTING: Academic center from November 2008 to January 2016. PATIENTS: Hospitalized patients outside the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six criteria were investigated: 1) any culture, 2) blood culture, 3) any culture plus IV antibiotics, 4) blood culture plus IV antibiotics, 5) any culture plus IV antibiotics for at least 4 of 7 days, and 6) blood culture plus IV antibiotics for at least 4 of 7 days. Accuracy of the quick Sepsis-related Organ Failure Assessment score, Sepsis-related Organ Failure Assessment score, systemic inflammatory response syndrome criteria, the National and Modified Early Warning Score, and the electronic Cardiac Arrest Risk Triage score were calculated for predicting ICU transfer or death within 48 hours of meeting suspicion criteria. A total of 53,849 patients met at least one infection criteria. Mortality increased from 3% for group 1 to 9% for group 6 and percentage meeting Angus sepsis criteria increased from 20% to 40%. Across all criteria, score discrimination was lowest for systemic inflammatory response syndrome (median area under the receiver operating characteristic curve, 0.60) and Sepsis-related Organ Failure Assessment score (median area under the receiver operating characteristic curve, 0.62), intermediate for quick Sepsis-related Organ Failure Assessment (median area under the receiver operating characteristic curve, 0.65) and Modified Early Warning Score (median area under the receiver operating characteristic curve 0.67), and highest for National Early Warning Score (median area under the receiver operating characteristic curve 0.71) and electronic Cardiac Arrest Risk Triage (median area under the receiver operating characteristic curve 0.73). CONCLUSIONS: The choice of criteria to define a potentially infected population significantly impacts prevalence of mortality but has little impact on accuracy. Systemic inflammatory response syndrome was the least predictive and electronic Cardiac Arrest Risk Triage the most predictive regardless of how infection was defined.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

OBJECTIVE: Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. DESIGN: Multicenter, observational study SETTING: : Medical ICUs at three academic medical centers. PATIENTS: Adult patients (age ≥ 18 yr old) receiving medication therapy. INTERVENTIONS: All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). CONCLUSION: Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

New-onset atrial fibrillation is an independent predictor of mortality in medical intensive care unit patients.

BACKGROUND: Atrial fibrillation (AF) has been extensively studied in postoperative critically ill surgical patients, but little literature exists to describe the outcomes of patients in the medical intensive care unit (ICU). OBJECTIVES: To determine the incidence of new-onset AF in patients admitted to a medical ICU and if new-onset AF was associated with adverse clinical outcomes. METHODS: This was a single-center, retrospective study of all adult patients admitted to the medical ICU at an academic medical center for >24 hours between December 2008 and April 2010. Collected data included past medical history, incidence of new-onset AF, Acute Physiology and Chronic Health Evaluation II scores, organ failure, length of stay in the ICU and hospital, and in-hospital and 60-day survival. RESULTS: A total of 741 patients were included. New-onset AF occurred in 53 patients (7.2%). In-hospital mortality was significantly greater for patients with new-onset AF (45% vs 16%; adjusted odds ratio [OR] = 2.21, 95% CI 1.07-4.54, P = 0.032), as was 60-day mortality (51% vs 23%; adjusted OR = 1.99, 95% CI = 1.01-3.91, P = 0.047). Patients with new-onset AF experienced greater ICU (6 ± 10.2 days vs 3 ± 3.6 days, P < 0.01) and hospital (15 ± 19 days vs 7 ± 9 days, P < 0.01) lengths of stay. CONCLUSIONS: Medical ICU patients who developed new-onset AF experienced a 2-fold increase in the odds of in-hospital mortality and death at 60 days. Further research investigating contributing factors to new-onset AF and potential treatments is warranted.

Generation of Toxoplasma gondii and Hammondia hammondi Oocysts and Purification of Their Sporozoites for Downstream Manipulation.

Toxoplasma gondii tachyzoites and bradyzoites are studied extensively in the laboratory due to the ease with which they can be cultured. In contrast, oocysts and the sporozoites within them are more difficult to work with, in that cat infections are required for their generation and isolating sporozoites requires a laborious excystation procedure. More over some parasite species such as Hammondia hammondi are obligately heteroxenous and require passage through a cat for completion of the life cycle. There is no debate that there is great value in studying this important life cycle stage, and we present here a detailed description of the current protocols used in our laboratories to generate and isolate T. gondii and H. hammondi oocysts, and to excyst and purify the sporozoites within them for use in downstream experimental applications.

International Survey of Thrombolytic Use for Treatment of Cardiac Arrest Due to Massive Pulmonary Embolism.

OBJECTIVES: This survey sought to characterize the national prescribing patterns and barriers to the use of thrombolytic agents in the treatment of pulmonary embolism, with a specific focus on treatment during actual or imminent cardiac arrest. DESIGN: A 19-question international, cross-sectional survey on thrombolytic use in pulmonary embolism was developed, validated, and administered. A multivariable logistic regression was conducted to determine factors predictive of utilization of thrombolytics in the setting of cardiac arrest secondary to pulmonary embolism. SETTING: International survey study. SUBJECTS: Physicians, pharmacists, nurses, and other healthcare professionals who were members of the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thrombolytic users were compared with nonusers. Respondents (n = 272) predominately were physicians (62.1%) or pharmacists (30.5%) practicing in an academic medical center (54.8%) or community teaching setting (24.6%). Thrombolytic users (n = 177; 66.8%) were compared with nonusers (n = 88; 33.2%) Thrombolytic users were more likely to work in pulmonary/critical care (80.2% thrombolytic use vs 59.8%; p < 0.01) and emergency medicine (6.8% vs 3.5%; p < 0.01). Users were more likely to have an institutional guideline or policy in place pertaining to the use of thrombolytics in cardiac arrest (27.8% vs 13.6%; p < 0.01) or have a pulmonary embolism response team (38.6% vs 19.3%; p < 0.01). Lack of evidence supporting use and the risk of adverse outcomes were barriers to thrombolytic use. Working in a pulmonary/critical care environment (odds ratio, 2.36; 95% CI, 1.24-4.52) and comfort level (odds ratio, 2.77; 95% CI, 1.7-4.53) were predictive of thrombolytic use in the multivariable analysis. CONCLUSIONS: Most survey respondents used thrombolytics in the setting of cardiac arrest secondary to known or suspected pulmonary embolism. This survey study adds important data to the literature surrounding thrombolytics for pulmonary embolism as it describes thrombolytic user characteristic, barriers to use, and common prescribing practices internationally.

Implications of Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Early Management Bundle and Initial Lactate Measurement on the Management of Sepsis.

BACKGROUND: Sepsis remains a significant cause of morbidity and mortality in the United States, leading to the implementation of the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1). SEP-1 identifies patients with "severe sepsis" via clinical and laboratory criteria and mandates interventions, including lactate draws and antibiotics, within a specific time window. We sought to characterize the patients affected and to study the implications of SEP-1 on patient care and outcomes. METHODS: All adults admitted to the University of Chicago from November 2008 to January 2016 were eligible. Modified SEP-1 criteria were used to identify appropriate patients. Time to lactate draw and antibiotic and IV fluid administration were calculated. In-hospital mortality was examined. RESULTS: Lactates were measured within the mandated window 32% of the time on the ward (n = 505) compared with 55% (n = 818) in the ICU and 79% (n = 2,144) in the ED. Patients with delayed lactate measurements demonstrated the highest in-hospital mortality at 29%, with increased time to antibiotic administration (median time, 3.9 vs 2.0 h). Patients with initial lactates > 2.0 mmol/L demonstrated an increase in the odds of death with hourly delay in lactate measurement (OR, 1.02; 95% CI, 1.0003-1.05; P = .04). CONCLUSIONS: Delays in lactate measurement are associated with delayed antibiotics and increased mortality in patients with initial intermediate or elevated lactate levels. Systematic early lactate measurement for all patients with sepsis will lead to a significant increase in lactate draws that may prompt more rapid physician intervention for patients with abnormal initial values.

Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii.

Most eukaryotic parasites are obligately heteroxenous, requiring sequential infection of different host species in order to survive. Toxoplasma gondii is a rare exception to this rule, having a uniquely facultative heteroxenous life cycle. To understand the origins of this phenomenon, we compared development and stress responses in T. gondii to those of its its obligately heteroxenous relative, Hammondia hammondi and have identified multiple H. hammondi growth states that are distinct from those in T. gondii. Of these, the most dramatic difference was that H. hammondi was refractory to stressors that robustly induce cyst formation in T. gondii, and this was reflected most dramatically in its unchanging transcriptome after stress exposure. We also found that H. hammondi could be propagated in vitro for up to 8 days post-excystation, and we exploited this to generate the first ever transgenic H. hammondi line. Overall our data show that H. hammondi zoites grow as stringently regulated, unique life stages that are distinct from T. gondii tachyzoites, and implicate stress sensitivity as a potential developmental innovation that increased the flexibility of the T. gondii life cycle.

Association Between Opioid and Benzodiazepine Use and Clinical Deterioration in Ward Patients.

BACKGROUND: Opioids and benzodiazepines are frequently used in hospitals, but little is known about outcomes among ward patients receiving these medications. OBJECTIVE: To determine the association between opioid and benzodiazepine administration and clinical deterioration. DESIGN: Observational cohort study. SETTING: 500-bed academic urban tertiary-care hospital. PATIENTS: All adults hospitalized on the wards from November 2008 to January 2016 were included. Patients who were "comfort care" status, had tracheostomies, sickle-cell disease, and patients at risk for alcohol withdrawal or seizures were excluded. MEASUREMENTS: The primary outcome was the composite of intensive care unit transfer or ward cardiac arrest. Discrete-time survival analysis was used to calculate the odds of this outcome during exposed time periods compared to unexposed time periods with respect to the medications of interest, with adjustment for patient demographics, comorbidities, severity of illness, and pain score. RESULTS: In total, 120,518 admissions from 67,097 patients were included, with 67% of admissions involving opioids, and 21% involving benzodiazepines. After adjustment, each equivalent of 15 mg oral morphine was associated with a 1.9% increase in the odds of the primary outcome within 6 hours (odds ratio [OR], 1.019; 95% confidence interval [CI], 1.013-1.026; P < 0.001), and each 1 mg oral lorazepam equivalent was associated with a 29% increase in the odds of the composite outcome within 6 hours (OR, 1.29; CI, 1.16- 1.45; P < 0.001). CONCLUSION: Among ward patients, opioids were associated with increased risk for clinical deterioration in the 6 hours after administration. Benzodiazepines were associated with even higher risk. These results have implications for ward-monitoring strategies. Journal of Hospital Medicine 2017;12:428-434.