Hyperammonemia in the Pediatric Emergency Department.

ABSTRACT: Hyperammonemia is a serious clinical condition associated with significant morbidity and mortality. In the pediatric population, this is often caused by urea cycle disorders, acute liver failure, or other less common underlying etiologies. Children and teens with hyperammonemia can have a broad range of clinical findings, including vomiting, respiratory distress, and changes in mental status. As ammonia levels worsen, this presentation can progress to respiratory failure, encephalopathy, cerebral edema, seizures, and death. Given the risk of neurologic damage, timely identification and management of hyperammonemia is critical and includes initial resuscitation, early consultation with subspecialists, and initiation of appropriate therapies. It is important for pediatric emergency medicine providers to understand the clinical findings, causes, diagnosis, and management of hyperammonemia because they play a key role in the provision of effective, multidisciplinary care of these patients.

Direct-to-patient telemedicine: Expanding access to regional pediatric specialty care.

Telemedicine is seen as a useful tool in reducing gaps in health care but this technology-enabled care can also exacerbate health inequity if not implemented with a focus on inclusivity. Though many studies have reported improvements as well as exacerbation of disparities in access to care in their telehealth programs, there does not exist a common evaluation tool to assess these programs. To mitigate the impact of COVID-19 on health care workers and protect medically vulnerable children, in March 2020 we expanded our pre-established specialty and subspecialty direct-to-patient pediatric telemedicine program in a high volume urban pediatric health system. Our program aimed to prevent disparities in pediatric health care. In this study, using a "Pillars of Access" approach as a model to evaluate impact and access to care of our direct-to-patient telemedicine program, we analyzed the patients that were seen pre-COVID versus post-COVID. Our study demonstrated an increase in telemedicine visits for patients from diverse socioeconomic and racial backgrounds, and geographically underserved communities. We also observed an increase in telemedicine visits for mental health complaints and for certain categories of high-risk patients. This study was not designed to identify language and cultural barriers to telemedicine. Future identification of these specific barriers is needed. The tool to evaluate telehealth impact/access to care through a "Pillars of Access" approach presented here could serve as a model for implementation of telehealth programs. Our study highlights telemedicine programs as a mechanism to address healthcare inequity and overcome barriers to care.

Urban environmental exposures during the first 2000 days of life as a foundation for health across the life-course: a scoping review.

OBJECTIVES: By 2030, 60% of the global population is expected to live in urban areas. Exposure to urban environments during the first 2000 days of life can have positive or negative health outcomes across the life course. Understanding the types of urban exposures that influence health outcomes is needed to guide research priorities for public health and urban planning. This review aims to summarise the published research examining the health outcomes of all urban environmental exposures during the first 2000 days of life, identify the quantity and characteristics of research in this area, methods used, and knowledge gaps. METHODS: We conducted a scoping review using the JBI methodology for scoping reviews. Eight databases were searched for peer-reviewed primary studies. Inclusion criteria were studies that measured maternal, infant and child exposure to everyday urban environment features and conditions in cities/metropolitan areas during the first 2000 days of life and reported offspring health outcomes across the life course, including embryo, fetal/newborn, infant, child, adolescent, and adult outcomes. We used Covidence software for data screening and extraction. Study characteristics and findings were summarised using tables and narrative synthesis. RESULTS: We reviewed 235 articles, which included studies conducted across 41 countries, the majority in the US (n = 63). A broad range of environmental exposures were studied, spanning seven categories: air pollution; energy-based pollution; atmosphere, chemical and metal exposure; neighbourhood-built and natural environment features; neighbourhood community conditions; and residential living conditions. Air pollution was the most studied exposure type (n = 153 studies). Health outcomes were reported for all life stages except adults, with fetal/newborn outcomes the most studied life stage (n = 137). CONCLUSIONS: We found that most research investigating urban environmental exposures in the first 2000 days and health outcomes across the life course focused on air pollution exposures and fetal/newborn health outcomes, using correlational retrospective cohort designs. Few studies included multiple environmental exposures. There is a clear need for more longitudinal research to determine the health impacts of multiple urban environmental exposures across the life course. This will assist in developing urban design and planning strategies and population health to mitigate health risks across the life course.

Delays in treatment and disposition attributable to undertriage of pediatric emergency medicine patients.

BACKGROUND: Triage, the initial assessment and sorting of patients in the Emergency Department (ED), determines priority of evaluation and treatment. Little is known about the impact of undertriage, the underestimation of disease severity at triage, on clinical care in pediatric ED patients. We evaluate the impact of undertriage on time to disposition and treatment decisions in pediatric ED patients. METHODS: This was a case control study of ED visits for patients <22 years of age, with an assigned Emergency Severity Index (ESI) score of 4 or 5, and associated hospital admission, nebulized treatment, supplemental oxygen, and/or intravenous (IV) line placement, between January 1, 2018, to June 30, 2022. Controls were sampled from a pool of patient visits with an ESI score of 3, matched by intervention, disposition, and date and hour of arrival. Primary outcome measures were time to order of intervention (nebulized treatment, oxygen administration, or IV placement) and time to disposition decision. A secondary outcome measure was return visits requiring admission or emergency intervention within 14 days of the index visit. Continuous variables (time to orders) were analyzed using Wilcoxon rank sum test and dichotomous outcomes (return visits) were compared using odds ratios with 95% confidence intervals. Analysis was performed with Python v3.10. RESULTS: The final analysis included 7245 undertriaged patients. Undertriaged patients had longer times to orders for nebulized treatments, (p < 0.001) IV placement, (p < 0.001) and admission (p < 0.001) when compared to controls. There were no significant differences in time to supplemental oxygen delivery and time to discharge compared to controls. Undertriaged patients were more likely to experience a return visit requiring admission or emergency intervention (OR 3.74, 95% CI 3.32,4.22). CONCLUSIONS: Undertriage in the pediatric ED is associated with delays in care and disposition decisions and increases likelihood of return visits.

Undertriage for Children With Caregivers Preferring Languages Other Than English.

OBJECTIVES: Undertriage, the underestimation of acuity, can result in delayed care and potential morbidity in the emergency department (ED). Although inequities in ED care based on language preference have been noted, little is known about its association with undertriage. We evaluated for differences in undertriage based on caregiver language preference. METHODS: This was a retrospective cross-sectional study of patients aged younger than 21 years, triaged as Emergency Severity Index (ESI) level 4 or 5 (nonurgent), to the pediatric ED from January 1, 2019, through January 31, 2021. Indicators of undertriage were defined as hospital admission, significant ED resource use, or return visits with admission. We used logistic regression with generalized estimating equations to measure the association of preferred language with undertriage. RESULTS: Of 114 266 ED visits included in the study, 22 525 (19.8%) represented patients with caregivers preferring languages other than English. These children were more likely to experience undertriage compared with those with caregivers preferring English (3.7% [English] versus 4.6% [Spanish] versus 5.9% [other languages]; Spanish versus English: odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.4] and other languages versus English: OR, 1.6; 95% CI, 1.2-2.2). Differences remained after adjusting for sex, insurance, mode of arrival, and clustering by triage nurse (Spanish versus English: adjusted OR, 1.3; 95% CI, 1.3-1.5) and other languages versus English: adjusted OR, 1.6; 95% CI, 1.2-2.2). CONCLUSIONS: Children accompanied by caregivers preferring languages other than English are more likely to be undertriaged in the pediatric ED. Efforts to improve the triage process are needed to promote equitable care for this population.

Resident Communication With Patients and Families Preferring Languages Other Than English.

OBJECTIVES: Patients and families preferring languages other than English (LOE) often experience inequitable communication with their health care providers, including the underutilization of professional interpretation. This study had 2 aims: to characterize resident-perceived communication with families preferring LOE and to evaluate the impact of language preference on frequency of resident interactions with hospitalized patients and families. METHODS: This was a cross-sectional study at a quaternary care children's hospital. We developed a questionnaire for residents regarding their interactions with patients preferring LOE. We concurrently developed a communication tracking tool to measure the frequency of resident communication events with hospitalized patients. Data were analyzed with logistic and Poisson regression models. RESULTS: Questionnaire results demonstrated a high level of resident comfort with interpretation, though more than 30% of residents reported "sometimes" or "usually" communicating with families preferring LOE without appropriate interpretation (response rate, 47%). The communication tracking tool was completed by 36 unique residents regarding 151 patients, with a 95% completion rate. Results demonstrated that patients and families preferring LOE were less likely to be present on rounds compared with their counterparts preferring English (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.07-0.39). Similarly, patients and families preferring LOE were less likely to receive a resident update after rounds (adjusted odds ratio, 0.29; 95% CI, 0.13-0.62) and received fewer resident updates overall (incidence rate ratio, 0.45; 95% CI, 0.30-0.69). CONCLUSIONS: Hospitalized patients and families preferring LOE experience significant communication-related inequities. Ongoing efforts are needed to promote equitable communication with this population and should consider the unique role of residents.

Primary Palliative Care for Pediatric Residents: A Curricular Framework and Pilot.

PROBLEM: Palliative care (PC) is high-value, holistic care for a child and their family across the entire arc of an illness. All physicians should be competent in symptom management and providing goal-concordant care that acknowledges the quality of life; however, there is insufficient education in pediatric residency to develop competence in basic or ..úPrimary..Ñ PC. APPROACH: We completed a needs assessment and developed a longitudinal, comprehensive, and integrated primary PC curriculum for pediatric residents with the goal of developing foundational primary PC skills regardless of eventual career trajectory. After 1 year of implementation, we assessed resident comfort with primary PC skills via a retrospective pre-post survey. OUTCOMES: We found a statistically significant (P.ß<.ß.05) increase in residents... comfort with pain management, delivering serious news, and discussing goals of care. An increase in comfort with the management of other symptoms was not statistically significant. NEXT STEPS: After 1 year of implementation, residents describe an increase in comfort with primary PC skills. The next steps include more rigorous evaluation and expansion to include more education in medical ethics. While the educational need is universal, resident needs are constantly evolving and each institution should tailor this curriculum to fit their specific trainee needs and institutional expertise.

Medication Rounds: A Tool to Promote Medication Safety for Children with Medical Complexity.

Children with medical complexity (CMC) often have lengthy medication lists and are at risk of experiencing suboptimal medication management. This tool tutorial describes a novel and pragmatic strategy for the development and implementation of medication rounds, a model that promotes medication safety for hospitalized CMC. An interprofessional group designed and implemented a pharmacy-led medication rounding care model, in which clinicians and pharmacists partner weekly to conduct reviews of all patient medications on a general pediatrics CMC team using a comprehensive checklist. This approach fosters medication safety for hospitalized CMC and could be adapted to other complex inpatient populations.

A Quality Improvement Initiative to Improve Patient Safety Event Reporting by Residents.

INTRODUCTION: Residents play a key role in patient care at academic medical centers and have unique insights into safety improvement opportunities. At our institution, <1% of safety events were reported by resident trainees. The primary objective of this quality improvement (QI) initiative was to increase the monthly incidence of event reporting by pediatric residents by 20% from baseline within 12 months. METHODS: A QI team used the model for improvement to identify barriers to submitting safety event reports. The team used multiple intervention cycles to increase knowledge and promote engagement in event reporting. Interventions included educational tip sheets, a hospital-wide Morbidity and Mortality (M&M) conference, peer recognition and acknowledgment by senior leadership for report submission, and an interactive reporting activity. The outcome measure was monthly number of reports filed by residents. The process measure was the number of unique residents submitting a report each month. Time to complete a report was a balancing measure. RESULTS: The number of reports placed by residents increased significantly, with a centerline shift from 15 to 29 reports per month (statistical process control chart-Fig. 3). The number of unique residents submitting reports increased from 10 to 22 per month. The time to complete a report was unchanged. CONCLUSIONS: Engaging residents in patient safety initiatives through education, experiential learning, and recognition can increase safety event reporting by residents. Future planned interventions include enhancing safety event reporting technology, developing patient safety faculty and resident champions, and increasing transparency regarding outcomes of safety event reports.

EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression.

Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs. To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma, breast, and colon cancer. Here we studied peripheral blood samples of 48 prostate cancer (PCA) patients including hormone sensitive and castration resistant sub-groups. Blood samples were analyzed for three different properties including our own CSV-based CTC enumeration (using 84-1 mAb against CSV), CellSearch-based epithelial CTC counts, and serum prostate-specific antigen (PSA) quantification. Our data demonstrated that in comparison with CellSearch, the CSV-based method had greater sensitivity and specificity. Further, we observed significantly greater numbers of CTCs in castration resistant patients as measured by our CSV method but not CellSearch. Our data suggests CSV-guided CTC enumeration may hold prognostic value and should be further validated as a possible measurement of PCA progression towards the deadly, androgen-independent form.

Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients.

Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models.

Pharmacokinetics of fixed-dose combinations of empagliflozin/metformin compared with individual tablets in healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of fixed-dose combination (FDC) tablets of empagliflozin/metformin with individual tablets taken together. METHODS: In 3 randomized, open-label studies, healthy subjects received a single FDC tablet of empagliflozin/metformin in 1 of 6 dose combinations (empagliflozin 12.5 mg or 5 mg; metformin 500 mg, 850 mg, or 1,000 mg) in 1 period and the individual tablets taken together under fed conditions in another period. Empagliflozin 12.5 mg/metformin 1,000 mg FDC and individual tablets were also given under fasted conditions. RESULTS: Adjusted geometric mean ratios (GMRs) of empagliflozin area under the plasma concentration-time curve (AUC(0-∞)) for the FDCs vs. individual tablets ranged from 97.92 to 106.00%, and 90% CIs ranged from 93.53 to 109.39%. Adjusted GMRs of empagliflozin maximum plasma concentrations (C(max)) for the FDCs vs. individual tablets ranged from 100.97 to 106.52%, and 90% CIs ranged from 95.86 to 118.35%. Adjusted GMRs of metformin AUC(0-∞) for the FDCs vs. individual tablets ranged from 96.25 to 101.61%, and 90% CIs ranged from 88.54 to 106.62%. Adjusted GMRs of metformin C(max) for the FDCs vs. individual tablets ranged from 93.83 to 102.95%, and 90% CIs ranged from 88.01 to 109.08%. Bioequivalence was also established under fasted conditions for empagliflozin 12.5 mg/metformin 1,000 mg FDC vs. individual tablets taken together. All treatments were well tolerated. CONCLUSION: Empagliflozin/metformin FDC tablets were found to be bioequivalent to individual tablets taken together at all tested dose strengths.