Improving Time to Antibiotic Administration for Pediatric Oncology Patients With New-Onset Fever.

PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.

Repurposing Atovaquone as a Therapeutic against Acute Myeloid Leukemia (AML): Combination with Conventional Chemotherapy Is Feasible and Well Tolerated.

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) and blood/marrow pharmacokinetics (PK) were collected during Induction 1. Correlative studies assessed AQ-induced apoptosis and effects on OXPHOS. PDX models were treated with AQ. A total of 26 patients enrolled (ages 7.2 months-19.7 years, median 12 years); 24 were evaluable. A total of 14 (58%) and 19 (79%) evaluable patients achieved plasma concentrations above the known anti-leukemia concentration (>10 µM) by day 11 and at the end of Induction, respectively. Seven (29%) patients achieved adequate concentrations for PJP prophylaxis (>40 µM). Mean ease of administration score was 3.8. Correlative studies with AQ in patient samples demonstrated robust apoptosis, OXPHOS suppression, and prolonged survival in PDX models. Combining AQ with chemotherapy for AML appears feasible and safe in pediatric patients during Induction 1 and shows single-agent anti-leukemic effects in PDX models. AQ appears to be an ideal concomitant AML therapeutic but may require intra-patient dose adjustment to achieve concentrations sufficient for PJP prophylaxis.

Prison Culture as Rape Supportive: Applying Importation and Deprivation Models to Examine Inmate Beliefs.

While research examining sexual violence in prison has increased over the past 15 years, relatively scant attention has been paid to rape supportive beliefs and the factors influencing inmate adherence to these beliefs. Given the demonstrated role from studies outside the prison context that rape supportive beliefs have on sexual violence, important parallels can be drawn from studying the inmate population. Importation and deprivation models have been used to explain how inmates adapt to prison life-whether attitudes and behaviors are imported from their lives outside prison or are developed in prison due to the conditions of incarceration. Using a sample of male and female inmates (n = 875) from a large state prison system in the southern United States, the researchers explored the degree to which inmate rape supportive beliefs (IRSB) were influenced by variables indicative of importation or deprivation models of prison adaption. Findings revealed greater support for importation variables among both male and female inmates. With some variation, measures such as gender, age, ethnicity, and education were significant in explaining IRSB, similar to findings of studies on rape supportive beliefs among noninmate samples. Because these beliefs can manifest in problematic attitudes and behaviors among inmates, such as prison sexual violence and the underreporting of such violence, it is important that correctional administrators understand this relationship and take steps to lessen IRSB. Since IRSB largely correlate with factors unrelated to conditions of confinement, efforts to educate and sensitize inmates to prison sexual violence can replicate best practices based on populations outside of prisons.

Women with a substance use disorder: Treatment completion, pregnancy, and compulsory treatment.

Over the last several decades, research regarding substance use treatment programs has focused on the unique and differential outcomes of male and female illicit substance users. Research less frequently examines the unique individual and contextual factors that may influence treatment outcomes. One such population that merits special consideration is pregnant women, as substance use within this population has deleterious effects for both the women and their unborn children. The current study employs propensity score matching to determine if pregnancy and referral source to treatment affect treatment program outcomes. Findings suggest that pregnant women, compared to similarly situated nonpregnant women, are significantly less likely to complete substance use treatment; however, pregnant women who were referred to treatment by the criminal justice system were significantly more likely to complete treatment than those who entered treatment by other referral sources.

Evaluation of Chest Radiographs of Children with Newly Diagnosed Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the diagnostic yield of baseline chest radiographs (CXRs) of children with acute lymphoblastic leukemia (ALL). STUDY DESIGN: We reviewed the CXR findings at diagnosis for 990 patients aged 1-18 years with ALL treated during the Total XV and XVI studies at St. Jude Children's Research Hospital and evaluated the associations of these findings with clinical characteristics and initial management. RESULTS: Common findings were peribronchial/perihilar thickening (n = 187 [19.0%]), pulmonary opacity/infiltrate (n = 159 [16.1%]), pleural effusion/thickening (n = 109 [11.1%]), mediastinal mass (n = 107 [10.9%]), and cardiomegaly (n = 68 [6.9%]). Portable CXRs provided results comparable with those obtained with 2-view films. Forty of 107 patients with a mediastinal mass (37.4%) had tracheal deviation/compression. Mediastinal mass, pleural effusion/thickening, and tracheal deviation/compression were more often associated with T-cell ALL than with B-cell ALL (P < .001 for all). Pulmonary opacity/infiltrate was associated with younger age (P = .003) and was more common in T-cell ALL than in B-cell ALL (P = .001). Peribronchial/perihilar thickening was associated with younger age (P < .001) and with positive central nervous system disease (P = .012). Patients with cardiomegaly were younger (P = .031), more often black than white (P = .007), and more often categorized as low risk than standard/high risk (P = .017). Patients with a mediastinal mass, pleural effusion/thickening, tracheal deviation/compression, or pulmonary opacity/infiltrate were more likely to receive less invasive sedation and more intensive care unit admissions and respiratory support (P ≤ .001 for all). Cardiomegaly was associated with intensive care unit admission (P = .008). No patients died of cardiorespiratory events during the initial 7 days of management. CONCLUSIONS: The CXR can detect various intrathoracic lesions and is helpful in planning initial management.