Pharmacist Metrics in the Pediatric Intensive Care Unit: an Exploration of the Medication Regimen Complexity-Intensive Care Unit (MRC-ICU) Score.

INTRODUCTION: The medication regimen complexity-intensive care unit (MRC-ICU) score has been developed and validated as an objective predictive metric for patient outcomes and pharmacist workload in the adult critically ill population. The purpose of this study was to explore the MRC-ICU and other workload metrics in the pediatric ICU (PICU). METHODS: This study was a retrospective cohort of pediatric ICU patients admitted to a single institution -between February 2, 2022 - August 2, 2022. Two scores were calculated, including the MRC-ICU and the pediatric Daily Monitoring System (pDMS). Data were extracted from the electronic health record. The primary outcome was the correlation of the MRC-ICU to mortality, as measured by Pearson -correlation -coefficient. Additionally, the correlation of MRC-ICU to number of orders was evaluated. Secondary -analyses explored the correlation of the MRC-ICU with pDMS and with hospital and ICU length of stay. RESULTS: A total of 2,232 patients were included comprising 2,405 encounters. The average age was 6.9 years (standard deviation [SD] 6.3 years). The average MRC-ICU score was 3.0 (SD 3.8). For the primary outcome, MRC-ICU was significantly positively correlated to mortality (0.22 95% confidence interval [CI 0.18 - 0.26]), p<0.05. Additionally, MRC-ICU was significantly positively correlated to ICU length of stay (0.38 [CI 0.34 - 0.41]), p<0.05. The correlation between the MRC-ICU and pDMS was (0.72 [CI 0.70 - 0.73]), p<0.05. CONCLUSION: In this pilot study, MRC-ICU demonstrated an association with existing prioritization metrics and with mortality and length of ICU stay in PICU population. Further, larger scale studies are required.

Between-hospital variation in clinical decision support availability for common inpatient pediatric conditions: Results of a national Pediatric Research in Inpatient Settings (PRIS) Network survey.

Implementing pediatric-focused clinical decision support (CDS) into hospital electronic health records can lead to improvements in patient care and accelerate quality improvement and research initiatives. However, its design, development, and implementation can be a time-consuming and costly endeavor that may not be feasible for all hospital settings. In this cross-sectional study, we surveyed Pediatric Research in Inpatient Settings (PRIS) Network hospitals about the availability of CDS tools to gain an understanding of the functionality available across 8 common inpatient pediatric diagnoses. Among the conditions, asthma had the most extensive CDS availability, while mood disorders had the least. Overall, freestanding children's hospitals had the greatest breadth in CDS coverage across conditions and depth in CDS types within conditions. Future initiatives should examine the relationship between CDS availability and clinical outcomes as well as its relationship with hospitals' performance executing multicenter informatics projects, quality improvement collaboratives, and implementation science strategies.

Reducing Therapeutic Duplication in Inpatient Medication Orders.

BACKGROUND: Therapeutic duplication, the presence of multiple agents prescribed for the same indication without clarification for when each should be used, can contribute to serious medical errors. Joint Commission standards require that orders contain clarifying information about when each order should be given. In our system, as needed (PRN) acetaminophen and ibuprofen orders are major contributors to therapeutic duplication. OBJECTIVE: The objective of this study is to design and evaluate effectiveness of clinical decision support (CDS) to reduce therapeutic duplication with acetaminophen and ibuprofen orders. METHODS: This study was done in a pediatric health system with three freestanding hospitals. We iteratively designed and implemented two CDS strategies aimed at reducing the therapeutic duplication with these agents: (1) interruptive alert prompting clinicians for clarifying PRN comments at order entry and (2) addition of discrete "first-line" and "second-line" PRN reasons to orders. Therapeutic duplications were measured by manual review of orders for 30-day periods before and after each intervention and 6 months later. RESULTS: Therapeutic duplications decreased from 1,485 in the 30 days prior to the first alert implementation to 818 in the 30 days after but rose back to 1,208 in the 30 days prior to the second intervention. After discrete reasons were added to the order, therapeutic duplication decreased to 336 in the immediate 30 days and 6 months later remained at 277. Alerts firing rates decreased from 76.0 per 1,000 PRN acetaminophen or ibuprofen orders to 42.9 after the second intervention. CONCLUSION: Interruptive alerts may reduce therapeutic duplication but are associated with high rates of user frustration and alert fatigue. Leveraging discrete PRN reasons for "first line" and "second line" produced a greater reduction in therapeutic duplication as well as fewer interruptive alerts and less manual entry for providers.

Characteristics of Emergency Room and Hospital Encounters Resulting From Consumer Home Monitors.

BACKGROUND AND OBJECTIVES: Consumer home monitors (CHM), which measure vital signs, are popular products marketed to detect airway obstruction and arrhythmia. Yet, they lack evidence of infant death prevention, demonstrate suboptimal accuracy, and may result in false alarms that prompt unnecessary acute care visits. To better understand the hospital utilization and costs of CHM, we characterized emergency department (ED) and hospital encounters associated with CHM use at a children's hospital. METHODS: We used structured query language to search the free text of all ED and admission notes between January 2013 and December 2019 to identify clinical documentation discussing CHM use. Two physicians independently reviewed the presence of CHM use and categorized encounter characteristics. RESULTS: Evidence of CHM use contributed to the presentation of 36 encounters in a sample of over 300 000 encounters, with nearly half occurring in 2019. The leading discharge diagnoses were viral infection (13, 36%), gastroesophageal reflux (8, 22%) and false positive alarm (6, 17%). Median encounter duration was 20 hours (interquartile range: 3 hours to 2 days; max 10.5 days) and median cost of encounters was $2188 (interquartile range: $255 to $7632; max $84 928). CONCLUSIONS: Although the annual rate of CHM-related encounters was low and did not indicate a major public health burden, for individual families who present to the ED or hospital for concerns related to CHMs, there may be important adverse financial and emotional consequences.

Clinical Decision Support Stewardship: Best Practices and Techniques to Monitor and Improve Interruptive Alerts.

Interruptive clinical decision support systems, both within and outside of electronic health records, are a resource that should be used sparingly and monitored closely. Excessive use of interruptive alerting can quickly lead to alert fatigue and decreased effectiveness and ignoring of alerts. In this review, we discuss the evidence for effective alert stewardship as well as practices and methods we have found useful to assess interruptive alert burden, reduce excessive firings, optimize alert effectiveness, and establish quality governance at our institutions. We also discuss the importance of a holistic view of the alerting ecosystem beyond the electronic health record.

Alert burden in pediatric hospitals: a cross-sectional analysis of six academic pediatric health systems using novel metrics.

BACKGROUND: Excessive electronic health record (EHR) alerts reduce the salience of actionable alerts. Little is known about the frequency of interruptive alerts across health systems and how the choice of metric affects which users appear to have the highest alert burden. OBJECTIVE: (1) Analyze alert burden by alert type, care setting, provider type, and individual provider across 6 pediatric health systems. (2) Compare alert burden using different metrics. MATERIALS AND METHODS: We analyzed interruptive alert firings logged in EHR databases at 6 pediatric health systems from 2016-2019 using 4 metrics: (1) alerts per patient encounter, (2) alerts per inpatient-day, (3) alerts per 100 orders, and (4) alerts per unique clinician days (calendar days with at least 1 EHR log in the system). We assessed intra- and interinstitutional variation and how alert burden rankings differed based on the chosen metric. RESULTS: Alert burden varied widely across institutions, ranging from 0.06 to 0.76 firings per encounter, 0.22 to 1.06 firings per inpatient-day, 0.98 to 17.42 per 100 orders, and 0.08 to 3.34 firings per clinician day logged in the EHR. Custom alerts accounted for the greatest burden at all 6 sites. The rank order of institutions by alert burden was similar regardless of which alert burden metric was chosen. Within institutions, the alert burden metric choice substantially affected which provider types and care settings appeared to experience the highest alert burden. CONCLUSION: Estimates of the clinical areas with highest alert burden varied substantially by institution and based on the metric used.

Safety of Automatic End Dates for Antimicrobial Orders to Facilitate Stewardship.

Following implementation of automatic end dates for antimicrobial orders to facilitate antimicrobial stewardship at a large, academic children's hospital, no differences were observed in patient mortality, length of stay, or readmission rates, even among patients with documented bacteremia. Infect Control Hosp Epidemiol 2016;37:974-978.

Heterologous immunity triggered by a single, latent virus in Mus musculus: combined costimulation- and adhesion- blockade decrease rejection.

The mechanisms underlying latent-virus-mediated heterologous immunity, and subsequent transplant rejection, especially in the setting of T cell costimulation blockade, remain undetermined. To address this, we have utilized MHV68 to develop a rodent model of latent virus-induced heterologous alloimmunity. MHV68 infection was correlated with multimodal immune deviation, which included increased secretion of CXCL9 and CXCL10, and with the expansion of a CD8(dim) T cell population. CD8(dim) T cells exhibited decreased expression of multiple costimulation molecules and increased expression of two adhesion molecules, LFA-1 and VLA-4. In the setting of MHV68 latency, recipients demonstrated accelerated costimulation blockade-resistant rejection of skin allografts compared to non-infected animals (MST 13.5 d in infected animals vs 22 d in non-infected animals, p<.0001). In contrast, the duration of graft acceptance was equivalent between non-infected and infected animals when treated with combined anti-LFA-1/anti-VLA-4 adhesion blockade (MST 24 d for non-infected and 27 d for infected, p = n.s.). The combination of CTLA-4-Ig/anti-CD154-based costimulation blockade+anti-LFA-1/anti-VLA-4-based adhesion blockade led to prolonged graft acceptance in both non-infected and infected cohorts (MST>100 d for both, p<.0001 versus costimulation blockade for either). While in the non-infected cohort, either CTLA-4-Ig or anti-CD154 alone could effectively pair with adhesion blockade to prolong allograft acceptance, in infected animals, the prolonged acceptance of skin grafts could only be recapitulated when anti-LFA-1 and anti-VLA-4 antibodies were combined with anti-CD154 (without CTLA-4-Ig, MST>100 d). Graft acceptance was significantly impaired when CTLA-4-Ig alone (no anti-CD154) was combined with adhesion blockade (MST 41 d). These results suggest that in the setting of MHV68 infection, synergy occurs predominantly between adhesion pathways and CD154-based costimulation, and that combined targeting of both pathways may be required to overcome the increased risk of rejection that occurs in the setting of latent-virus-mediated immune deviation.

GVHD after haploidentical transplantation: a novel, MHC-defined rhesus macaque model identifies CD28- CD8+ T cells as a reservoir of breakthrough T-cell proliferation during costimulation blockade and sirolimus-based immunosuppression.

We have developed a major histocompatibility complex-defined primate model of graft-versus-host disease (GVHD) and have determined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this disease. Severe GVHD developed after haploidentical transplantation without prophylaxis, characterized by rapid clinical decline and widespread T-cell infiltration and organ damage. Mechanistic analysis showed activation and possible counter-regulation, with rapid T-cell expansion and accumulation of CD8(+) and CD4(+) granzyme B(+) effector cells and FoxP3(pos)/CD27(high)/CD25(pos)/CD127(low) CD4(+) T cells. CD8(+) cells down-regulated CD127 and BCl-2 and up-regulated Ki-67, consistent with a highly activated, proliferative profile. A cytokine storm also occurred, with GVHD-specific secretion of interleukin-1 receptor antagonist (IL-1Ra), IL-18, and CCL4. Costimulation Blockade and Sirolimus (CoBS) resulted in striking protection against GVHD. At the 30-day primary endpoint, CoBS-treated recipients showed 100% survival compared with no survival in untreated recipients. CoBS treatment resulted in survival, increasing from 11.6 to 62 days (P < .01) with blunting of T-cell expansion and activation. Some CoBS-treated animals did eventually develop GVHD, with both clinical and histopathologic evidence of smoldering disease. The reservoir of CoBS-resistant breakthrough immune activation included secretion of interferon-γ, IL-2, monocyte chemotactic protein-1, and IL-12/IL-23 and proliferation of cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-resistant CD28(-) CD8(+) T cells, suggesting adjuvant treatments targeting this subpopulation will be needed for full disease control.

Overweight/obesity and gastric fluid characteristics in pediatric day surgery: implications for fasting guidelines and pulmonary aspiration risk.

BACKGROUND: The safety of 2-h preoperative clear liquid fasts has not been established for overweight/obese pediatric day surgical patients. Healthy children and obese adults who fasted 2 h have small residual gastric fluid volumes (GFVs), which are thought to reflect low pulmonary aspiration risk. We sought to measure the prevalence of overweight/obesity in our day surgery population. We hypothesized that neither body mass index (BMI) percentile nor fasting duration would significantly affect GFV or gastric fluid pH. In children who were allowed clear liquids up until 2 h before surgery, we hypothesized that overweight/obese subjects would not have increased GFV over lean/normal subjects and that emesis/pulmonary aspiration events would be rare. METHODS: Demographics, medical history, height, and weight were recorded for 1000 consecutive day surgery patients aged 2-12 yr. In addition, 1000 day surgery patients (age 2-12 yr) undergoing general endotracheal anesthesia were enrolled. After tracheal intubation, a 14-18F orogastric tube was inserted and gastric contents evacuated. Medications, fasting interval, GFV, pH, and emetic episodes were documented. Age- and gender-specific Center for Disease Control and Prevention growth charts (2000) were used to determine ideal body weight (IBW = 50th percentile) and to classify patients as lean/normal (BMI 25th-75th percentile), overweight (BMI > or = 85th to <95th percentile), or obese (BMI > or = 95th percentile). RESULTS: Of all day surgery patients, 14.0% were overweight and 13.3% were obese. Obese children had lower GFV per total body weight (P < 0.001). When corrected for IBW, however, volumes GFV(IBW) were identical across all BMI categories (mean 0.96 mL/kg, sd 0.71; median 0.86 mL/kg, IQR 0.96). Preoperative acetaminophen and midazolam contributed to increased GFV(IBW) (P = 0.025 and P = 0.001). Lower GFV(IBW) was associated with ASA physical status III (P = 0.024), male gender (P = 0.012), gastroesophageal reflux disease (P = 0.049), and proton pump inhibitor administration (P = 0.018). GFV(IBW) did not correlate with fasting duration or age. Decreased gastric fluid acidity was associated with younger age (P = 0.005), increased BMI percentile (P = 0.036), and African American race (P = 0.033). Emesis on induction occurred in eight patients (50% of whom were obese, P = 0.052, and 75% of whom had obstructive sleep apnea, P = 0.061). Emesis was associated with increased ASA physical status (P = 0.006) but not with fasting duration. There were no pulmonary aspiration events. CONCLUSIONS: Twenty-seven percent of pediatric day surgery patients are overweight/obese. These children may be allowed clear liquids 2 h before surgery as GFV(IBW) averages 1 mL/kg regardless of BMI and fasting interval. Rare emetic episodes were not associated with shortened fasting intervals in this population.