Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis.

Importance: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. Objective: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. Design, Setting, and Participants: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. Exposure: The number of minutes from emergency department arrival to antibiotic administration. Main Outcomes and Measures: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. Results: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. Conclusions and Relevance: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Improving Guideline-Based Care of Acute Asthma in a Pediatric Emergency Department.

BACKGROUND AND OBJECTIVE: Rapid repetitive administration of short-acting ß-agonists (SABA) is the most effective means of reducing acute airflow obstruction in asthma. Little evidence exists that assesses process measures (ie, timeliness) and outcomes for asthma. We used quality improvement (QI) methods to improve emergency department care in accordance with national guidelines including timely SABA administration and use of asthma severity scores. METHODS: The Model for Improvement was used and interventions were targeted at 4 key drivers: knowledge, engagement, decision support, and workflow enhancement. Time series analysis was performed and outcomes assessed on statistical process control charts. RESULTS: Asthma severity scoring increased from 0% to >95% in triage and to >75% for repeat scores. Time to first SABA (T1) improved by 32.8 minutes (47%). T1 for low severity patients improved by 17.6 minutes (28%). T1 for high severity patients improved by 3.1 minutes to 18.1 minutes (15%). Time to third SABA (T3) improved by 30 minutes (24%). T3 for low severity patients improved by 42.5 minutes (29%) and T3 for high severity patients improved by 21 minutes (23%). Emergency department length of stay for low severity patients discharged to home improved by 29.3 minutes (15%). The number of asthma-related visits between 48-hour return hospitalizations increased from 114 to 261. The admission rate decreased 6.0%. CONCLUSIONS: We implemented standardized asthma severity scoring with high rates of compliance, improved timely administration of ß-agonist treatments, demonstrated early improvements in Emergency department length of stay, and reduced admission rates without increasing unplanned return admissions.

Dexamethasone for acute asthma exacerbations in children: a meta-analysis.

BACKGROUND AND OBJECTIVE: Dexamethasone has been proposed as an equivalent therapy to prednisone/prednisolone for acute asthma exacerbations in pediatric patients. Although multiple small trials exist, clear consensus data are lacking. This systematic review and meta-analysis aimed to determine whether intramuscular or oral dexamethasone is equivalent or superior to a 5-day course of oral prednisone or prednisolone. The primary outcome of interest was return visits or hospital readmissions. METHODS: A search of PubMed (Medline) through October 19, 2013, by using the keywords dexamethasone or decadron and asthma or status asthmaticus identified potential studies. Six randomized controlled trials in the emergency department of children ≤18 years of age comparing dexamethasone with prednisone/prednisolone for the treatment of acute asthma exacerbations were included. Data were abstracted by 4 authors and verified by a second author. Two reviewers evaluated study quality independently and interrater agreement was assessed. RESULTS: There was no difference in relative risk (RR) of relapse between the 2 groups at any time point (5 days RR 0.90, 95% confidence interval [CI] 0.46-1.78, Q = 1.86, df = 3, I2 = 0.0%, 10-14 days RR 1.14, 95% CI 0.77-1.67, Q = 0.84, df = 2, I2 = 0.0%, or 30 days RR 1.20, 95% CI 0.03-56.93). Patients who received dexamethasone were less likely to experience vomiting in either the emergency department (RR 0.29, 95% CI 0.12-0.69, Q = 3.78, df = 3, I2 = 20.7%) or at home (RR 0.32, 95% CI 0.14-0.74, Q = 2.09, df = 2, I2 = 4.2%). CONCLUSIONS: Practitioners should consider single or 2-dose regimens of dexamethasone as a viable alternative to a 5-day course of prednisone/prednisolone.

Prolonged coma in a child due to hashish ingestion with quantitation of THC metabolites in urine.

BACKGROUND: Cannabinoid-containing substances are commonly abused worldwide. Significant toxicity from these substances is uncommon in adults but can result in significant symptoms in children; these symptoms are usually short-lived. OBJECTIVES: To report a case of prolonged mental status alteration of more than 2 days in a child who ingested hashish. CASE REPORT: A 14-month-old child presented comatose to a pediatric emergency department after ingestion of hashish; she did not regain consciousness for more than 48 h. Quantitative testing of the child's urine for a tetrahydrocannabinol metabolite revealed a markedly elevated level, the decline of which coincided with the child's clinical improvement. CONCLUSIONS: Significant ingestion of cannabinoid-containing substances is capable of causing prolonged symptoms (including coma) in children.

The pretransplant Follicular Lymphoma International Prognostic Index is associated with survival of follicular lymphoma patients undergoing autologous hematopoietic stem cell transplantation.

We retrospectively evaluated the association of the Follicular Lymphoma International Prognostic Index (FLIPI) and other characteristics with survival following high-dose therapy and autologous stem cell transplantation (ASCT) in 207 consecutive follicular lymphoma (FL) patients. The FLIPI was associated with OS both when evaluated as a categorical variable (0 - 1 vs. 2 vs. 3 vs. 4, p = 0.01, global test) and a continuous linear variable (p = 0.002). The association of FLIPI with survival appeared to be more relevant for patients who received standard conditioning regimens compared to those that were treated with high-dose radioimmunotherapy (p = 0.004). Among all patients, mortality was also associated with chemosensitive disease (HR = 0.47, p = 0.01) or untreated relapse (HR = 0.20, p = 0.0002) vs. chemoresistant disease, and > or =2 extranodal sites (HR = 2.82, p = 0.03) after adjusting for FLIPI. These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT.

The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation.

The foreign body reaction (FBR) develops in response to the implantation of almost all biomaterials and can be detrimental to their function. The formation of foreign body giant cells (FBGC), which damage the surface of biomaterials, is considered a hallmark of this reaction. FBGC derive from blood-borne monocytes that enter the implantation site after surgery in response to the release of chemotactic signals. In this study, we implanted biomaterials subcutaneous (s.c.) in mice that lack the monocyte chemoattractant CC chemokine ligand 2 (CCL2) and found that biomaterials were encapsulated despite reduced FBGC formation. The latter was due to compromised macrophage fusion rather than migration. Consistent with the reduction in FBGC formation, biodegradable biomaterials sustained reduced damage in CCL2-null mice. Furthermore, blockade of CCL2 function by localized gene delivery in wild-type mice hindered FBGC formation, despite normal monocyte recruitment. The requirement for CCL2 in fusion was confirmed by the ability of both a CCL2 inhibitory peptide and an anti-CCL2 Ab to reduce FBGC formation from peripheral blood monocytes in an in vitro assay. Our findings demonstrate a previously unreported involvement of CCL2 in FBGC formation, and suggest that FBGC are not the primary determinants of capsule formation in the FBR.