Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study

Background Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61–0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44–0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64–1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Post-release of the symposium «How to Deal with Pain in the 21st Century? Expert Opinions» (November 8, 2021, XII Interdisciplinary International Congress «Manage Pain»)

The article presents the chronology of the symposium «How to Deal with Pain in the 21st Century? Experts' opinions», which took place on November 8 during the XII interdisciplinary international congress «Manage Pain». The lectures discussed issues of non-steroidal anti-inflammatory drugs (NSAIDs), including etoricoxib (Atorika tabs), administration on the example of a clinical case, problems of terminology associated with the concepts of «lumbago» and «sciatica», rare clinical syndromes (for example, heavy-purse syndrome) that we need to differentiate nonspecific back pain with, strategies for choosing NSAIDs in patients with osteoarthritis, the importance of timely administration of NSAIDs in the prevention of chronic pain syndromes, the influence of emotional and cognitive factors on the back pain chronization. The benefits of etoricoxib (Atorika) in the treatment of chronic back pain were reviewed, as well as the evidence for its safety.

The pronounced decline of anti-SARS-CoV-2 spike trimeric IgG and RBD IgG in baseline seronegative individuals 6 months after BNT162b2 vaccination is consistent with the need for vaccine boosters

Background: This observational retrospective study aimed to define the kinetics of serum levels of anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) spike trimeric and anti-receptor binding domain (RBD) IgG antibodies up to 6 months after BNT162b2 vaccination. Methods: The sample consisted of 86 SARS-CoV-2 baseline seronegative subjects (median age 45 years, IQR 31-53 years; 52.3% females) undergoing vaccination with Pfizer/BioNTech BNT162b2. Blood was drawn before receiving the first and the second vaccine dose, as well as 1, 3 and 6 months after the second vaccine dose. The serum levels of anti-SARS-CoV-2 spike trimeric IgG and RBD IgG antibodies were assayed.Results: The peak of both antibodies types was reached 1 month after the second dose (2808 and 2163 BAU/mL for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG), after which serum levels progressively declined, falling after 6 months to 486 BAU/mL and 167 BAU/mL for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively. The median rate of 6-month decline was 85% and 93% for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively. The rate of vaccine recipients with serum antibodies levels above the 80% threshold of vaccine efficacy declined from over 95% at the peak to 72% and 5% at 6 months for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively.Conclusions: The results of this retrospective observational study are consistent with the need for timely administration of vaccine boosters to prevent that humoral immunity will wane.

Implementation of a Physician Incentivized QI Strategy to Address Time to Parenteral Analgesia in Patients with Voe in the Pediatric Emergency Department

Introduction Vaso-occlusive episodes (VOE) are the most common cause of pediatric Emergency Department (ED) visits and hospitalizations in Sickle Cell Disease (SCD). The National Heart Lung and Blood Institute published an Expert Panel Report regarding the management of SCD and VOE. Their consensus statement recommends initiating analgesic therapy within 30 minutes of triage or within 60 minutes of registration in the Emergency Department. Previous studies have demonstrated that earlier maximum opioid has been associated with shorter length of hospitalization and improved time to ED disposition decision. Despite the overwhelming evidence for timely administration of parenteral analgesic, significant delays still exist in delivery of pain medication in the pediatric SCD population. Barriers to timely administration include rapid triage of SCD patients, provider ordering of pain medication, and peripheral intravenous access. Therefore, a standardized approach to pain management may improve ED management of SCD crises. In order to address timely administration of opiates to SCD patients with VOE episodes in our pediatric ED a SCD pain order set was developed. This order set implemented the use of intranasal (IN) fentanyl as a first line analgesic for SCD patients who presents to the ED with VOE. The purpose of this study was addressing barriers to decrease time to parenteral opioid administration in the pediatric ED. Methods This Quality Improvement (QI) measure was performed at a free-standing, urban pediatric ED. Patients were included if they had a diagnosis of SCD and presented with a pain score >5 and without fever. A PDSA cycle was utilized for designing and evaluating the proposed changes. This cycle consisted of three intervention phases: (1) electronic medical record (EMR) order set development in October 2019, (2) provider incentive for order set use in January 2020, and (3) nursing/patient & family education in April 2020. Baseline data was collected pre-intervention from April-September 2019. The outcomes measures were mean time to 1 st analgesic, mean time from triage to disposition, Hospital Length of Stay, and overall admission rates. Our balancing measure included 48 hour ED re-visits after discharge. Results There were 67 ED visits from April-September 2019 (pre-intervention) and 104 ED visits in the post-intervention data from October-June 2020. There was no significant difference in age or initial pain score in the pre- and post- intervention groups. Improvements were seen in: mean time to first analgesic (58 to 26 minutes), time to disposition (271 to 213 minutes). Hospital length of stay was found to increase with the introduction of IN fentanyl: pre-intervention (120 hours), phase 1 (148 hours), phase 2 (152 hours), phase 3 (218 hours). However, the overall admission rate decreased (55% to 44%). The number of 48-hour ED re-visits remained stable. Conclusion By using QI methods to address key barriers in the pediatric ED, we demonstrated that timely administration of parenteral analgesic can be achieved for SCD patients with VOE. Utilizing the EMR order set allowed for more stream-lined care, both by physicians and nursing staff, resulting in more rapid ordering of medication therefore decreasing time to ED disposition. Additional interventions such as provider incentivization to meet the goal of parenteral opioids within 30 minutes of patient arrival led to further improvement. One of the greatest barriers to our QI intervention was hesitancy both by patients and their caregivers regarding the efficacy of IN fentanyl in decreasing pain compared to IV opioid. Further education was needed both for families and medical staff regarding the efficacy of IN fentanyl as a first line analgesic. It is unclear why overall hospital length of stay was not shown to be decreased with these interventions but this can be offset by an overall decrease in hospital admissions seen with our interventions. This data may be limited by the SARS-CoV-2 pandemic and how psychosocial stressors can impact patients with chronic medical conditions. Length of stay is also confounded by other factors during the hospitalization and acquisition of other diagnoses such as acute chest. Future research is needed to determine if the demonstrated trend of admission rates and hospital length of stay can be replicated in other pediatric EDs and whether earlier opioid administration affects the outcome of VOEs beyond the ED. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

533. Protocol for and Efficacy of Monoclonal Antibody (mAb) Treatment of SARS-CoV-2 at a VA Medical Center

Background Bamlanivimab and casirivimab/imdevimab were the first monoclonal antibodies (mAb) developed against SARS-CoV-2 and proved beneficial early in the course of infection. However, real-world administration of these therapies presents logistical challenges. We present our experience implementing mAb treatment at a large VA Medical Center and review the efficacy of therapy in preventing hospitalization from COVID-19 in a closed healthcare system. Methods All positive outpatient COVID tests performed at VA Greater Los Angeles Healthcare System (GLA) were reviewed by the Emergency Medicine (EM) and Infectious Diseases (ID) Sections for mAb eligibility beginning 12/2/2020. Due to limited supply, treatment was prioritized for patients at highest risk of developing severe disease, as determined by EM/ID with input from a machine learning ensemble risk estimation model produced by VA National Artificial Intelligence Institute (Figure 1). If a patient declined or did not reply, treatment was offered to the next patient on a ranked eligibility list. Those who declined or were eligible but not treated were included in the analysis. Patients were excluded if they were hospitalized before treatment was offered. We collected data on age, comorbidities, date of diagnosis, and admission at 30 days after diagnosis. A multivariate log binomial regression was performed to determine the relative risk of admission within 30 days of diagnosis for those who received mAb therapy as compared to those who did not, adjusting for age and comorbidity. All analysis was done in R (version 4.0.5). Results 139 patients met inclusion criteria. 45 (32%) received mAb therapy, 48 (35%) declined mAb therapy, and the remaining 46 (33%) either did not respond or were not offered mAb therapy. Hospitalizations following diagnosis in each group are illustrated in Figure 2. There was a trend towards reduced absolute and relative risk of hospitalization (Table 1). There were no anaphylactic events in patients who received mAb therapy. Conclusion At our facility, a system for rapid identification of candidates and a coordinated distribution plan was essential in ensuring timely administration of mAb therapy to eligible patients. Administration of mAb showed a trend towards decreased risk of hospitalization due to SARS-CoV-2. Disclosures Adela Greeley, MD, Kite (Other Financial or Material Support, My spouse is an employee) Matthew B. Goetz, MD, Nothing to disclose

Artificial intelligence sepsis prediction algorithm learns to say “I don’t know”

Sepsis is a leading cause of morbidity and mortality worldwide. Early identification of sepsis is important as it allows timely administration of potentially life-saving resuscitation and antimicrobial therapy. We present COMPOSER (COnformal Multidimensional Prediction Of SEpsis Risk), a deep learning model for the early prediction of sepsis, specifically designed to reduce false alarms by detecting unfamiliar patients/situations arising from erroneous data, missingness, distributional shift and data drifts. COMPOSER flags these unfamiliar cases as indeterminate rather than making spurious predictions. Six patient cohorts (515,720 patients) curated from two healthcare systems in the United States across intensive care units (ICU) and emergency departments (ED) were used to train and externally and temporally validate this model. In a sequential prediction setting, COMPOSER achieved a consistently high area under the curve (AUC) (ICU: 0.925–0.953; ED: 0.938–0.945). Out of over 6 million prediction windows roughly 20% and 8% were identified as indeterminate amongst non-septic and septic patients, respectively. COMPOSER provided early warning within a clinically actionable timeframe (ICU: 12.2 [3.2 22.8] and ED: 2.1 [0.8 4.5] hours prior to first antibiotics order) across all six cohorts, thus allowing for identification and prioritization of patients at high risk for sepsis.

Time to Antibiotics in Pediatric Patients with Fever in Neutropenia during Chemotherapy for Cancer -- Data from the Prospective Multicenter SPOG 2015 FN Definition Study

Background. Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. Procedure. We analyzed the association between time from recognition of fever to start of antibiotics (F-TTA) and SRE (death, admission to intensive care unit (ICU), severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation. Results. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. F-TTA (median, 120min; interquartile range, 49 to 180min) was not associated with SRE, with a trend for less SREs in episodes with longer F-TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. Conclusion. We found little evidence that longer TTA leads to a higher risk of poor clinical outcome in pediatric patients with FN, except for those with severe disease at presentation. We saw strong evidence for triage bias which could only be partially adjusted.

SOSIALISASI PENGGUNAAN ANTIBIOTIK CEFTRIAXONE PADA PASIEN DEMAM TYFOID ANAK DI INSTALASI RAWAT INAP RSUD DELI SERDANG

Typhoid fever is a systemic infection caused by the salmonella thypi bacteria which attacks the small intestine with fever for 1 week or more accompanied by disturbances in the digestive tract. This disease is endemic and is a community disease that is transmitted through food and drink contaminated with bacteria. Typhoid fever can be treated using antibiotics, giving antibiotics especially in children and infants must consider the side effects on body systems and organ function that are still not perfect. The purpose of this study was to determine the use of ceftriaxone antibiotics based on the right indication, appropriate patient, appropriate medication, proper dosage, timely administration of the drug and the right way of giving antibiotics in the inpatient installation of the Deli Serdang Regional General Hospital in 2019. This study used retrospective data and was analyzed descriptively by purposive sampling method. Data used by pediatric patients (2-12 years). Data according to the inclusion characteristics of 43 cases were evaluated for their quality based on the right indication, appropriate patient, appropriate medication, proper dosage, the right time of administration and the right way of administration. The results of this study indicate that the percentage of the quality of antibiotic use includes 43 (100%) right indications, 43 (100%) right patients, 43 (100%) right drugs, 30 (73%) right doses, 42 right time of administration ( 97.67%) and the right way of giving was 43 (100%).

Network Mapping of Time to Antithrombotic Therapy Among Patients With Ischemic Stroke and Transient Ischemic Attack (TIA)

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.