The impact of antibiotic timing on sepsis outcomes remains controversial due to conflicting results from previous studies.
This study investigated the association of door-to-antibiotic time with ...long-term mortality in ED patients with sepsis.
This retrospective cohort study included nontrauma adult ED patients with clinical sepsis admitted to four hospitals from 2013 to 2017. Only patients’ first eligible encounter was included. Multivariable logistic regression was used to measure the adjusted association between door-to-antibiotic time and 1-year mortality. Secondary analyses used alternative antibiotic timing measures (antibiotic initiation within 1 or 3 h and separate comparison of antibiotic exposure at each hour up to hour 6), alternative outcomes (hospital, 30-day, and 90-day mortality), and alternative statistical methods to mitigate indication bias.
Among 10,811 eligible patients, median door-to-antibiotic time was 166 min (interquartile range, 115-230 min), and 1-year mortality was 19%. After adjustment, each additional hour from ED arrival to antibiotic initiation was associated with a 10% (95% CI, 5-14; P < .001) increased odds of 1-year mortality. The association remained linear when each 1-h interval of door-to-antibiotic time was independently compared with door-to-antibiotic time ≤ 1 h and was similar for hospital, 30-day, and 90-day mortality. Mortality at 1 year was higher when door-to-antibiotic times were > 3 h vs ≤ 3 h (adjusted OR, 1.27; 95% CI, 1.13-1.43) but not > 1 h vs ≤ 1 h (adjusted OR, 1.26; 95% CI, 0.98-1.62).
Delays in ED antibiotic initiation time are associated with clinically important increases in long-term, risk-adjusted sepsis mortality.
Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established.
To ...assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2.
Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication.
On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years IQR, 46-59; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar.
Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated.
ClinicalTrials.gov Identifier: NCT04498273.
The Charlson and Elixhauser comorbidity indices are mortality predictors often used in clinical, administrative, and research applications. The Intermountain Mortality Risk Scores (IMRS) are ...validated mortality predictors that use all factors from the complete blood count and basic metabolic profile. How IMRS, Charlson, and Elixhauser relate to each other is unknown.
All inpatient admissions except obstetric patients at Intermountain Healthcare's 21 adult care hospitals from 2010-2014 (N = 197,680) were examined in a observational cohort study. The most recent admission was a patient's index encounter. Follow-up to 2018 used hospital death records, Utah death certificates, and the Social Security death master file. Three Charlson versions, 8 Elixhauser versions, and 3 IMRS formulations were evaluated in Cox regression and the one of each that was most predictive was used in dual risk score mortality analyses (in-hospital, 30-day, 1-year, and 5-year mortality).
Indices with the strongest mortality associations and selected for dual score study were the age-adjusted Charlson, the van Walraven version of the acute Elixhauser, and the 1-year IMRS. For in-hospital mortality, Charlson (c = 0.719; HR = 4.75, 95% CI = 4.45, 5.07), Elixhauser (c = 0.783; HR = 5.79, CI = 5.41, 6.19), and IMRS (c = 0.821; HR = 17.95, CI = 15.90, 20.26) were significant predictors (p<0.001) in univariate analyses. Dual score analysis of Charlson (HR = 1.79, CI = 1.66, 1.92) with IMRS (HR = 13.10, CI = 11.53, 14.87) and of Elixhauser (HR = 3.00, CI = 2.80, 3.21) with IMRS (HR = 11.42, CI = 10.09, 12.92) found significance for both scores in each model. Results were similar for 30-day, 1-year, and 5-year mortality.
IMRS provided the strongest ability to predict mortality, adding to and attenuating the predictive ability of the Charlson and Elixhauser indices whose mortality associations remained statistically significant. IMRS uses common, standardized, objective laboratory data and should be further evaluated for integration into mortality risk evaluations.
Prompt sepsis treatment is associated with improved outcomes but requires a complex series of actions by multiple clinicians. We investigated whether simply reorganizing emergency department (ED) ...care to expedite patients' initial evaluation was associated with shorter sepsis door-to-antibiotic times.
Patients eligible for this retrospective study received IV antibiotics and demonstrated acute organ failure after presenting to one of three EDs in Utah. On May 1, 2016, the intervention ED instituted "swarming" as the default model for initial evaluation of all mid- and low-acuity patients. Swarming involved simultaneous patient evaluation by the ED physician, nurse, and technician followed by a team discussion of the initial care plan. Care was unchanged at the two control EDs. A 30-day wash-in period separated the baseline (May 16, 2015 to April 15, 2016) and post-intervention (May 16, 2016 to November 15, 2016) analysis periods. We conducted a quasi-experimental analysis comparing door-to-antibiotic time for sepsis patients at the intervention ED after versus before care reorganization, applying difference-in-differences methods to control for trends in door-to-antibiotic time unrelated to the studied intervention and multivariable regression to adjust for patient characteristics.
The analysis included 3,230 ED sepsis patients, including 1,406 from the intervention ED. Adjusted analyses using difference-in-differences methods to control for temporal trends unrelated to the studied intervention revealed no significant change in door-to-antibiotic time after care reorganization (-7 minutes, 95% CI -20 to 6 minutes, p = 0.29). Multivariable pre/post analyses using data only from the intervention ED overestimated the magnitude and statistical significance of outcome changes associated with ED care reorganization.
Implementation of an ED care model involving parallel multidisciplinary assessment and early team discussion of the care plan was not associated with improvements in mid- and low-acuity sepsis patients' door-to-antibiotic time after accounting for changes in the outcome unrelated to the studied intervention.
The modified Brain Injury Guidelines (mBIG) support a subset of low-risk patients to be managed without repeat head computed tomography (RHCT), neurosurgical consult (NSC), or hospital ...transfer/admission. This pilot aimed to assess mBIG implementation at a single facility to inform future systemwide implementation.
Single cohort pilot trial at a level I trauma center, December 2021–August 2022. Adult patients included if tICH meeting BIG 1 or 2 criteria. BIG 3 patients excluded.
No patients required neurosurgical intervention. 72 RHCT and 83 NSC were prevented. 21 isolated BIG 1 were safely discharged home from the ED. No hospital readmissions for tICH. Protocol adherence rate was 92%.
Implementation of the mBIG at a single trauma center is feasible and optimizes resource utilization. This pilot study will inform an implementation trial of the mBIG across a 24-hospital integrated health system.
•Traumatic brain injury (TBI) is responsible for the utilization of significant healthcare, yet there is no widely accepted approach to management.•In current practice, management of TBI with intracranial hemorrhage is resource intensive and often beyond what patients need.•The modified Brain Injury Guideline allows management of low-risk TBI patients without repeat head CT, neurosurgical consult, or hospital admission.•The mBIG can safely and effectively improve resource utilization in patients with traumatic intracranial hemorrhage (ICH).
The efficacy and safety of managing patients with low-risk pulmonary embolism (PE) without hospitalization requires objective data from US medical centers. We sought to determine the 90-day composite ...rate of recurrent symptomatic VTE, major bleeding events, and all-cause mortality among consecutive patients diagnosed with acute low-risk PE managed without inpatient hospitalization; and to measure patient satisfaction.
We performed a prospective cohort single-arm management study conducted from January 2013 to October 2016 in five EDs. We enrolled 200 consecutive adults diagnosed with objectively confirmed acute PE and assessed to have a low risk for mortality using the Pulmonary Embolism Severity Index (PESI) score (< 86), echocardiography, and whole-leg compression ultrasound (CUS). The primary intervention was observation in the ED or hospital (observation status) for > 12 to < 24 h, followed by outpatient management with Food and Drug Administration-approved therapeutic anticoagulation. Patients were excluded for a PESI ≥ 86, echocardiographic signs of right heart strain, DVT proximal to the popliteal vein, hypoxia, hypotension, hepatic or renal failure, contraindication to therapeutic anticoagulation, or another condition requiring hospital admission. The primary outcome was 90-day composite rate of all-cause mortality, recurrent symptomatic VTE, and major bleeding.
The composite outcome occurred in one of 200 patients (90-day composite rate = 0.5%; 95% CI, 0.02%-2.36%). No patient suffered recurrent VTE or died during the 90-day follow-up period. A major bleed occurred in one patient. Patients indicated a high level of satisfaction with their care.
Treatment of carefully selected patients with acute PE and low risk by PESI < 86, echocardiography, and CUS without inpatient hospitalization is safe and acceptable to patients. Results must be viewed with caution because of the small sample size relative to the end point and the generalizability surrounding availability of emergent echocardiography.
ClinicalTrials.gov; No.: NCT02355548; URL: www.clinicaltrials.gov.
Reply to Adelman et al Hooper, Gabriel A; Stenehjem, Edward A; Bledsoe, Joseph R ...
Clinical infectious diseases,
07/2023, Volume:
77, Issue:
2
Journal Article
Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization, but there is a paucity of evidence to guide the use of post-discharge prophylaxis (PDP).
A retrospective ...cohort study of trauma patients deemed moderate-to-high risk for VTE (risk assessment profile score RAP ≥5) who were prescribed PDP based on an internal clinical guideline assessing injury pattern and mobility status. PDP patients were compared with those that did not receive post-discharge prophylaxis (NPDP).
1512 patients were included. PDP group had higher mean RAP score (7.3 vs. 6.4, p < 0.001), more likely to have a complex orthopedic fracture and underwent a longer median hospital (4.7 vs. 2.9 days, p < 0.001). No difference between groups in 90-day VTE (11 1.5 % (PDP) vs. 8 1.0 % (NPDP), p = 0.50), clinically relevant bleeding (p = 0.58), or readmission (p = 0.46).
VTE incidence, clinically relevant bleeding, and readmission 90-days after hospital discharge were low and similar between PDP and NPDP groups. PDP prescribed in a presumably higher VTE risk trauma population may mitigate the long-term risk of VTE.
•Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization.•Patients who received post-discharge prophylaxis (PDP) were at higher risk of VTE.•Incidence of 90-day post-discharge VTE, clinically relevant bleeding, and readmission were similar between groups suggesting mitigation of VTE in high risk trauma patients.
Barriers to early antibiotic administration for sepsis remain poorly understood. We investigated the association between emergency department (ED) crowding and door-to-antibiotic time in ED sepsis.
...We conducted a retrospective cohort study of ED sepsis patients presenting to 2 community hospitals, a regional referral hospital, and a tertiary teaching hospital. The primary exposure was ED occupancy rate, defined as the ratio of registered ED patients to licensed ED beds. We defined ED overcrowding as an ED occupancy rate greater than or equal to 1. We used multivariable regression to measure the adjusted association between ED crowding and door-to-antibiotic time (elapsed time from ED arrival to first antibiotic initiation). Using Markov multistate models, we also investigated the association between ED crowding and pre-antibiotic care processes.
Among 3,572 eligible sepsis patients, 70% arrived when the ED occupancy rate was greater than or equal to 0.5 and 14% arrived to an overcrowded ED. Median door-to-antibiotic time was 158 minutes (interquartile range 109 to 216 minutes). When the ED was overcrowded, 46% of patients received antibiotics within 3 hours of ED arrival compared with 63% when it was not (difference 14.4%; 95% confidence interval 9.7% to 19.2%). After adjustment, each 10% increase in ED occupancy rate was associated with a 4.0-minute increase (95% confidence interval 2.8 to 5.2 minutes) in door-to-antibiotic time and a decrease in the odds of antibiotic initiation within 3 hours (odds ratio 0.90; 95% confidence interval 0.88 to 0.93). Increasing ED crowding was associated with slower initial patient assessment but not further delays after the initial assessment.
ED crowding was associated with increased sepsis antibiotic delay. Hospitals must devise strategies to optimize sepsis antibiotic administration during periods of ED crowding.
Abstract
Background
Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of ...false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria.
Methods
For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in 1 of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression.
Results
Of 8267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication and 1488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (ie, initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n = 812), 79 (9.7%) had only “possible” infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an “unknown infection source” diagnosis in the ED (odds ratio: 6.39; 95% confidence interval: 5.14–7.94). False-positive infection diagnosis was not associated with 30-day mortality.
Conclusions
In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.
Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/concordance-between-initial-presumptive-versus-final-adjudicated-diagnoses-of-infection-among-patients-meeting-sepsis-3-criteria-in-the-emergency-department
In this large multihospital study, <20% of emergency department (ED) patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication and 18% of infected patients had a different source of infection diagnosed in the ED versus final adjudication.
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