Real-World Application of Recently Proposed ASTCT/CIBMTR/EBMT/APBMT Consensus Risk Stratification for Transplantation-Associated Thrombotic Microangiopathy in Children.

Consensus diagnostic and risk stratification of transplantation-associated thrombotic microangiopathy (TA-TMA) was recently achieved from international transplantation groups. Although the proposed diagnostic criteria have been applied to multiple pediatric cohorts, there are scant data applying the novel risk stratification approach in children with TA-TMA. In this retrospective cohort study, all children undergoing an allogeneic HCT or autologous HCT for neuroblastoma were prospectively screened for TA-TMA, diagnosed, and risk-stratified using the Jodele criteria from August 2019 to October 2023. Our institutional practice during the study period was treat all Jodele intermediate-risk (IR) and high-risk (HR) patients with eculizumab. Harmonization risk stratification criteria were applied retrospectively. All survival analyses were calculated from the day of TA-TMA diagnosis. To identify which specific harmonization high-risk features were the most important predictors for nonrelapse mortality (NRM), full and reduced logistical regression models were tested. The lowest Bayes information criterion and optimal Mallows CP statistic were used to identify the best subset. The analysis was performed with SAS 9.4 (SAS Institute, Cary, NC). Fifty-two children were diagnosed with TA-TMA during the study period, at a median of 37.5 days post-HCT (range, 3 to 735 days). Using Jodele risk stratification, 11 (21%) were SR, 21 (40%) were IR, and 20 (39%) were HR. Forty (77%) were treated with eculizumab. There were no statistically significant differences in NRM among Jodele risk groups, although overall survival (OS) differed significantly. Using the harmonized stratification, 49 children (94%) were stratified as HR and 3 as standard risk (SR), there were no statistically significant differences in NRM or OS between groups. Eight children (15.4%) were classified as SR using Jodele risk stratification but restratified as HR using the harmonization criteria. One child (12.5%) died in the setting of severe GVHD, and the remaining 7 were alive at the last follow-up. In a best subset model, lactate dehydrogenase (LDH) level >2 times the upper limit of normal (ULN) (odds ratio [OR], 6.52, 95% confidence interval [CI], .96 to 44.3; P = .05), grade II-IV acute graft-versus-host disease (GVHD) at the time of TA-TMA diagnosis (OR, 15.4; 95% CI, 2.14 to 110.68; P = .01), and organ dysfunction at the time of TA-TMA (OR, 21.5; 95% CI, 2.96 to 156.37; P = .002) were significantly associated with NRM; elevated sC5b-9, urine protein/creatinine ratio, and viral infections were not significantly associated with NRM. Using these best-fit criteria, 14 patients were classified as SR and 38 were classified as HR, NRM was significantly higher, and OS was significantly lower. In this cohort of children with TA-TMA, retrospective application of the harmonization criteria resulted in more patients stratified as HR compared to use of the previously described Jodele criteria. The intention of the harmonization criteria was to identify those at greatest risk of poor outcomes; while all harmonization SR patients survived, this risk stratification was very sensitive. Previous criticisms of harmonization risk stratification include limited access to sC5b-9 testing. These data suggest that organ dysfuncion, acute GVHD, and LDH >2 times ULN are the most important predictors of NRM in this cohort, allowing risk stratification even in the absence of available sC5b-9 testing. Additional studies are needed to validate these findings.

Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children.

Transplant-associated thrombotic microangiopathy (TA-TMA) and sickle cell disease (SCD) share features of endothelial and complement activation. Thus, we hypothesized that SCD is a risk factor for TA-TMA and that prehematopoietic cellular transplantation (HCT) markers of endothelial dysfunction and complement activation would be higher in patients with SCD. Children who underwent initial haploidentical or matched sibling donor HCT between January 2015 and June 2020 were included in this institutional review board-approved, single institution, retrospective study. Of the 115 children, 52 had SCD, and 63 underwent HCT for non-SCD indications. There was no significant difference in severe grade 3 to 4 acute graft-versus-host disease (GVHD) between recipients of HCT with or without SCD. The non-SCD cohort had significantly more cytomegalovirus-positive recipients, radiation-containing preparative regimens, and peripheral blood stem cell graft sources (P ≤ .05), all described risk factors for developing TA-TMA. Despite this, 7 of 52 patients (13%) with SCD developed TA-TMA compared with 1 of 63 patients (2%) without SCD (P = .015). Risk was highest in those who underwent haploidentical HCT (odds ratio [OR], 33; 95% confidence interval [CI], 1.4-793.2). Adjusting for HLA match, GVHD, post-HCT viral infection, stem cell source, and myeloablation, SCD remained a risk for developing TA-TMA (OR, 12.22; 95% CI, 1.15-129.6). In available pre-HCT samples, there was no difference in complement biomarkers between those with SCD and those without, though patients with SCD did have significantly higher levels of markers of endothelial activation, soluble vascular cell adhesion molecule 1, and P-selectin. In conclusion, children with SCD merit careful screening for TA-TMA after HCT, particularly those receiving a haploidentical HCT.

Short-Course Empiric Antibiotics in Children Undergoing Allogeneic Hematopoietic Cell Transplantation.

Fever is common in children undergoing hematopoietic cell transplantation (HCT). Empiric antibiotic (EA) therapy is initiated and often continued until neutrophil engraftment. Prolonged antibiotic exposure reduces microbiome diversity and causes overgrowth of pathogenic organisms, leading to such complications as infections from antibiotic-resistant organisms and Clostridium difficile colitis. Shorter courses of EA therapy have been studied in adults undergoing HCT without significant safety concerns, but data in children are lacking. We instituted a single-center preintervention/ postintervention quality improvement (QI) project to assess the feasibility of short-course EA therapy for first fever in patients undergoing HCT. We aimed to reduce the median duration of broad-spectrum antibiotic use in eligible patients from 20 days in 2020 to 10 days in 2021. Patients were eligible for the intervention, limiting EAs to 7 days for first fever, if they were admitted for their first allogeneic HCT, were afebrile for >24 hours, had no infection requiring systemic treatment, and were hemodynamically stable. Outcome measures included days of EA therapy for first fever and total broad-spectrum antibiotic use during the period of hospitalization, defined as the time from the start of conditioning to 30 days after HCT or hospital discharge, whichever occurred first. Balancing measures included bloodstream infection (BSI), fever, and intensive care (ICU) admission within 3 days of stopping EA therapy. Project criteria were applied retrospectively to patients who underwent HCT in 2020 to construct a preintervention short-course-eligible cohort. During the intervention period, 41 patients underwent allogeneic HCT, of whom 17 (41%) were eligible for short-course EA therapy. Among eligible patients, the median age was 5.3 years, 47% had an underlying malignancy, and 88% received myeloablative conditioning. There were no differences in demographic or HCT characteristics between patients eligible for short-course EA during the intervention and preintervention period (n = 24). The short-course EA schedule was adhered to by 14 of the 17 eligible patients (82%). The duration of EA for first fever and total broad-spectrum antibiotic use was significantly decreased in the short-course EA-eligible patients compared to the preintervention cohort, from a median of 17 days to 8 days and from 20 days to 10 days, respectively (P < .01). Of the 14 patients adhering to short-course EA, 2 experienced a balancing measure of recurrent fever requiring resumption of EA, but no infection was identified. There were no BSIs, ICU admissions, or deaths during the hospitalization period in patients who received short-course EA. In this single-center QI project, short-course EA for initial fever was successfully applied to children undergoing allogeneic HCT using strict criteria and led to a significant decrease in broad-spectrum antibiotic use during hospitalization. These results should be validated in a prospective clinical trial to include the impact of short-course EA on antibiotic-resistant organisms, the intestinal microbiome, and HCT outcomes.

Perceived Barriers to Rapid Response Team Activation Among Nurses.

The purpose of this literature review was to investigate the major barriers nurses face when it is necessary to seek additional assistance and resources by calling the rapid response team (RRT) in order to manage and stabilize a clinically deteriorating patient. A total of 40 articles were reviewed. Eight barriers were identified as having an impact on RRT activation, either causing a delay in activation time or preventing activation altogether: a lack of consistent RRT education among nurses, the established hierarchy in the hospital, an uncertainty about when to call the RRT if clinical deterioration is subtle or gradual rather than abrupt, a perceived need to justify a decision to call the RRT, the increased workload for both the ICU nurse and the medical-surgical nurse, negative past experiences with RRTs, an unsupportive unit culture, and less nursing experience. Suggestions for overcoming these barriers include RRT education for nurses and physicians in addition to fostering a supportive unit culture.

A pilot study on delirium in the intensive care unit: a creative inquiry project with undergraduate nursing students.

INTRODUCTION: Delirium continues to be a major issue in intensive care units (ICUs). Sedation and lack of rapid eye movement (REM) sleep could be important factors in the development of delirium. Improper sedation may interfere with a patient's sleep pattern, specifically time spent in REM sleep, and could be a contributor to the development of delirium. The research team has discovered through this pilot study that there is a possible correlation between sedation, disruptions, and sleep. The goal of our research was to determine the relationship between these variables using a sleep monitor to capture actual sleep activity compared with patient characteristics and real-time activity in the ICU environment. MATERIALS AND METHODS: This was a pilot study of 7 new patients, aged 65 years or older, who were intubated and sedated. Data on patient sleep cycles were collected using a wireless sleep monitor. A time sheet was placed outside each room to record time and type of interruption during nighttime hours (9 PM-6 AM). The patients were observed for 1 to 7 nights dependent on their length of stay in the ICU. RESULTS: Preliminary results demonstrated that, on average, between 9 PM and 6 AM, 48% remained awake (range, 8%-88%), 30% were in light sleep (range, 2%-50%), 18.5% were in REM (range, 2%-60%), and 3.4% were in a deep sleep (range, 0%-9%). Subject 1 remained awake 52% to 88% of the time during the entire admission of 7 days, had an Intensive Care Delirium Screening Checklist score of 5, and had a self-extubation; sedation ordered was Versed as needed. Subject 5 had no interventions done between 12 midnight and 4:50 AM, with the exception of turning once, and had an REM recorded of 60% on 1 night, which equals to 4 hours 49 minutes of rest. All patients with the exception of 1 were on fentanyl and Versed drips with varying dose adjustments throughout their admission. IMPLICATIONS: Preliminary results show that there is a relationship between lack of REM sleep and delirium. The pilot study was a useful model to demonstrate the need for further investigation in a larger population.

The RAVE-O Intervention: Connecting Neuroscience to the Classroom.

This article explores the ways in which knowledge from the cognitive neurosciences, linguistics, and education interact to deepen our understanding of reading's complexity and to inform reading intervention. We first describe how research on brain abnormalities and naming speed processes has shaped both our conceptualization of reading disabilities and the design of a multicomponent reading intervention, the RAVE-O program. We then discuss the unique ways this program seeks to address the multiple and varied sources of disruption in struggling readers. Finally, we present efficacy data for the RAVE-O reading intervention across multiple school settings.

Isopropyl alcohol inhalation as treatment for nausea and vomiting.

In my practice as a recovery room nurse, I had observed anesthesiologists and nurse anesthetists wave an opened alcohol preparation pad under a patient's nose when he or she complained of nausea. When asked, "Why?'' the response often was, "Because it works.'' The following article describes the use of inhalation of isopropyl alcohol as a treatment for postoperative nausea and vomiting. Because alcohol swabs are so readily available, and certainly less expensive than some of the newer antiemetics on the market, this simple nursing intervention was worth investigating.