Brenner Children's Hospital

Background Food allergy (FA) is associated with considerable anxiety and poorer quality-of-life (QOL) in caregivers. High self-efficacy for managing FA might reduce this impact but these relationships have not been examined with FA-specific measures.

Abstract Background Antimicrobial resistance (AMR) is a complex threat to global health security and universal health coverage. The continued escalation of AMR among Gram-negative bacteria (GNB) is a major concern due to the endemic presence of MDR and extremely drug-resistant (XDR) pathogens.In this regard, the present study aimed to asses the magnitude of MDR, its risk factors, and mortality in MDR/XDR - GNB. Methods GNB isolates were retrieved from patients, identified and assessed for antibiotic resistance pattern using VITEK® 2 compact system. The extended spectrum β-lactamase (ESBL) production in 100 GNB isolates was determined by double disk synergy test and genes confirmed by PCR in retrospective cohort study (2011-2012). The carbapenemase production in 100 isolates was confirmed by modified carbapenem inactivation method in prospective cross-sectional study (2021-2022). The metallo β-lactamase (MBLs) were screened by combined disk test and carbapenemase genes detected by multiplex-PCR. Minimum inhibitory concentration (MIC) of colistin was determined by Broth Micro dilution method and clonal relatedness was evaluated by Multilocus sequence typing (MLST). Results In retrospective study, all cases confirmed ESBL with high incidence of antibiotic resistance in cephalosporins,chloramphenicol and ciprofloxacin. All isolates were susceptible to carbapenem. bla TEM and bla CTX-M were prevalent ESBL genes, with 7 % mortality. In prospective study, isolates were positive for carbapenemase with XDR pattern and 47% of mortality. 90% isolates were MBLs positive and 30% had at least two carbapenemase genes, the combination of bla OXA-48 and bla NDM-1 was highly prevalent. Colistin resistance was observed in 20% and 30% isolates with 8 and 4 µg/ml MICs, respectively. Further, multiplex-PCR confirmed the mcr genes and clonal relatedness was determined. Conclusion The high prevalence rate of MDR-GNB from producing ESBLs (2011-12) to carbapenemase (2021-2022) was observed. Our results emphasize on antibiotic stewardship policies and regular surveillance programmes for monitoring AMR and screening of drug resistance genes. MLST, molecular surveillance, is valuable tool for rapid epidemiological investigation with precision in determining clonal relatedness Disclosures All Authors: No reported disclosures

Preterm newborns (PTNBs) often require sedation and analgesia. Dexmedetomidine (DEX) is used to provide sedation in extremely PTNBs, even though information on such use is limited. The objective of this research is to describe the use of DEX in these patients in a single academic center. This is a retrospective study of PTNBs receiving DEX from January 1, 2010, through December 31, 2018, at the Cleveland Clinic Children's Hospital, a tertiary academic center operating 2 Level III and 1 Level IV neonatal intensive care units (NICUs). Inclusion criteria were gestational age (GA) <36 weeks and receipt of DEX for >2 days. Adequacy of clinical response was based on achieving Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores <3. Hypotension, bradycardia, and respiratory depression were recorded as the incidence as adverse events. A total of 105 patients were included. The birth weight median was 870 g (IQR, 615-1507); the GA median was 26 weeks (IQR, 24-31). The duration of DEX infusion averaged 7 days. The DEX dose averaged 0.4 mcg/kg (IQR, 0.3-0.45). Bradycardia was observed in 35 patients (57%) weighting <1 kg and in 7 patients (18%) >1 kg (p < 0.01). There was no difference in the incidence of other adverse events between these groups. However, infants <1 kg required more pharmacologic interventions to maintain N-PASS score <3. DEX was well tolerated overall and provided adequate sedation to PTNBs in this cohort. From this study, we recommend a starting dose of 0.2 to 0.4 mcg/kg/hr and titrating up hourly until adequate sedation is achieved.

This study examined differences in clinical and resuscitation characteristics between injured children with and without severe traumatic brain injury (sTBI) and aimed to identify resuscitation characteristics associated with improved outcomes following sTBI. This is a post hoc analysis of a prospective observational study of injured children younger than 18 years (2018-2019) transported from the scene, with elevated shock index pediatric-adjusted on arrival and head Abbreviated Injury Scale score of ≥3. Timing and volume of resuscitation products were assessed using χ 2t test, Fisher's exact t test, Kruskal-Wallis, and multivariable logistic regression analyses. There were 142 patients with sTBI and 547 with non-sTBI injuries. Severe traumatic brain injury patients had lower initial hemoglobin (11.3 vs. 12.4, p < 0.001), greater initial international normalized ratio (1.4 vs. 1.1, p < 0.001), greater Injury Severity Score (25 vs. 5, p < 0.001), greater rates of ventilator (59% vs. 11%, p < 0.001) and intensive care unit (ICU) requirement (79% vs. 27%, p < 0.001), and more inpatient complications (18% vs. 3.3%, p < 0.001). Severe traumatic brain injury patients received more prehospital crystalloid (25% vs. 15%, p = 0.008), ≥1 crystalloid boluses (52% vs. 24%, p < 0.001), and blood transfusion (44% vs. 12%, p < 0.001) than non-sTBI patients. Among sTBI patients, receipt of ≥1 crystalloid bolus (n = 75) was associated with greater ICU need (92% vs. 64%, p < 0.001), longer median ICU (6 vs. 4 days, p = 0.027) and hospital stay (9 vs. 4 days, p < 0.001), and more in-hospital complications (31% vs. 7.5%, p = 0.003) than those who received <1 bolus (n = 67). These findings persisted after adjustment for Injury Severity Score (odds ratio, 3.4-4.4; all p < 0.010). Pediatric trauma patients with sTBI received more crystalloid than those without sTBI despite having a greater international normalized ratio at presentation and more frequently requiring blood products. Excessive crystalloid may be associated with worsened outcomes, including in-hospital mortality, seen among pediatric sTBI patients who received ≥1 crystalloid bolus. Further attention to a crystalloid sparing, early transfusion approach to resuscitation of children with sTBI is needed. Therapeutic/Care Management; Level IV.

Aminoglycosides are frequently used for empiric and definitive treatment of cystic fibrosis (CF) pulmonary exacerbations. Various methods have been described for aminoglycoside therapeutic drug monitoring. The objective of this study is to evaluate the effect of patient-specific pharmacokinetic calculations for aminoglycosides used to treat CF pulmonary exacerbations. Ambidirectional cohort study of patients admitted to a children's hospital from June 1, 2018, through February 28, 2019, and June 1, 2019, through February 8, 2021. The primary outcome was the occurrence of dosing changes after analysis of initial serum concentrations in either group. Secondary outcomes included occurrence of nephrotoxicity, duration of antibiotics, and length of stay. Twenty-four patients (75%) in the intervention group versus zero in the control group required dosing adjustments after initial analysis of serum concentrations were completed (p < 0.001). There was not a statistically significant between-group difference for duration of antibiotics in days (median, 14 vs 13.5; Z, 1.07; p = 0.29) or length of stay (median, 11 vs 11; Z, -0.31; p = 0.76). There was also not a statistically significant between-group difference in forced expiratory volume in one second (FEV1) change from admission to discharge (11.4% vs 13.9%; t, 0.61; Degrees of Freedom, 39; p = 0.55). Two patients (6.25%) in the intervention group experienced nephrotoxicity compared with zero patients in the control group (risk difference, 6.25%; 95% CI, -2.14 to 14.64; number needed to harm, 16). Patient-specific pharmacokinetic monitoring led to significantly more dosing changes and was associated with similar patient outcomes as trough-only monitoring. Further studies are needed to identify methods to optimize aminoglycoside dosing and monitoring for these patients with the goal of reducing toxicities while maximizing efficacy.

BackgroundMany countries have experienced 2 predominant waves of COVID-19–related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and health care dynamics of the COVID-19 pandemic.ObjectiveIn this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating health care systems representing 315 hospitals across 6 countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic.MethodsUsing a federated approach, each participating health care system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were adopted at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual health care system effect sizes and synthesizing these using random effect meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19.ResultsData were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50 to 69 years decreased significantly between the first and second waves. Patients hospitalized in the second wave had a 9.9% reduction in the risk of severe COVID-19 compared to patients hospitalized in the first wave (95% CI 8.5%-11.3%). Demographic subgroup analyses indicated that patients aged 26 to 49 years and 50 to 69 years; male and female patients; and black patients had significantly lower risk for severe disease in the second wave than in the first wave. At admission, the mean values of CRP were significantly lower in the second wave than in the first wave. On the seventh hospital day, the mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave than in the first wave. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain.ConclusionsPatients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international health care systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve.