Top Ten Tips Palliative Clinicians Should Know About Rural Palliative Care in the United States.

Palliative care improves outcomes, yet rural residents often lack adequate and equitable access. This study provides practical tips to address palliative care (PC)-related challenges in rural communities. Strategies include engaging trusted community partners, addressing cultural factors, improving pediatric care, utilizing telehealth, networking with rural teams including caregivers, and expanding roles for nurses and advanced practice providers. Despite complex barriers to access, providers can tailor PC to be patient-centered, respect local values, and bridge gaps. The "Top 10" format emphasizes the relevant issues to enable clinicians to provide optimal care for people from rural areas.

Signs and Behaviors to Identify Impairment and Drug Diversion.

Substance use disorder in health care professionals may adversely affect patient care. To reduce the risks of harm, raising awareness among all staff for early identification and response is a primary goal. Knowledgeable co-workers play an essential role to identify signs and behaviors indicating at-risk substance use by observed impairment or suspicion of drug diversion and report to a supervisor. Response protocol for a timely, confidential, safe and non-punitive intervention can help connect the clinician to needed assessment and treatment help and potentially save a life and provide a hopeful outcome to retain their license and career.

Hemodynamic and Respiratory Effects of Regadenoson During Radiologic Imaging in Infants and Children.

BACKGROUND: Myocardial perfusion imaging using radionuclides is a well-validated, noninvasive method to aid in the diagnosis of patients with suspected or known myocardial ischemia. To increase the sensitivity of the technique, pharmacologic agents which induce coronary vasodilatation are administered. Regadenoson is a novel selective A2A receptor agonist that has similar efficacy to adenosine for cardiac magnetic resonance imaging (MRI) with a more favorable adverse effect profile and is the most widely used pharmacologic stress agent. While widely used in adults, there is limited experience with it in pediatrics, particularly young children. METHODS: The current study retrospectively reviews our experience with stress cardiac MRI using regadenoson in children requiring general anesthesia. The study cohort included eight patients, all male, ranging in age from 2 to 6.2 years (mean age of 4.2 years) and in weight from 10 to 30.5 kg (mean weight of 18.5 kg). All patients received general anesthesia with endotracheal intubation and a volatile anesthetic agent. RESULTS: Heart rate 1 min prior to regadenoson was 99 ± 19.2 (mean ± standard deviation (SD)) beats per minute. Peak heart rate was achieved at an average of 4 min post regadenoson administration with a mean heart rate of 122 ± 15 beats per minute. The average of the mean arterial pressure 1 min prior to regadenoson was 53.4 ± 5.2 mm Hg. Mean arterial pressure nadir was noted at 6 min post regadenoson with a value of 44.1 ± 6.3 mm Hg. Blood pressure support with phenylephrine was required in four of the eight (50%) of patients. No adverse respiratory events were noted. Only one of the eight (13%) patients had a perfusion defect but had preserved ventricular function and recovered without incident. CONCLUSIONS: Use of regadenoson in pediatric patients requiring general anesthesia is safe and feasible.

Benchmark Concentrations for Untargeted Metabolomics Versus Transcriptomics for Liver Injury Compounds in In Vitro Liver Models.

Interpretation of untargeted metabolomics data from both in vivo and physiologically relevant in vitro model systems continues to be a significant challenge for toxicology research. Potency-based modeling of toxicological responses has served as a pillar of interpretive context and translation of testing data. In this study, we leverage the resolving power of concentration-response modeling through benchmark concentration (BMC) analysis to interpret untargeted metabolomics data from differentiated cultures of HepaRG cells exposed to a panel of reference compounds and integrate data in a potency-aligned framework with matched transcriptomic data. For this work, we characterized biological responses to classical human liver injury compounds and comparator compounds, known to not cause liver injury in humans, at 10 exposure concentrations in spent culture media by untargeted liquid chromatography-mass spectrometry analysis. The analyte features observed (with limited metabolites identified) were analyzed using BMC modeling to derive compound-induced points of departure. The results revealed liver injury compounds produced concentration-related increases in metabolomic response compared to those rarely associated with liver injury (ie, sucrose, potassium chloride). Moreover, the distributions of altered metabolomic features were largely comparable with those observed using high throughput transcriptomics, which were further extended to investigate the potential for in vitro observed biological responses to be observed in humans with exposures at therapeutic doses. These results demonstrate the utility of BMC modeling of untargeted metabolomics data as a sensitive and quantitative indicator of human liver injury potential.

Simulation-based curriculum development: lessons learnt in Global Health education.

BACKGROUND: Simulation based medical education (SBME) allows learners to acquire clinical skills without exposing patients to unnecessary risk. This is especially applicable to Emergency Medicine training programs where residents are expected to demonstrate proficiency in the management of time critical, low frequency, and highly-morbidity conditions. This study aims to describe the process through which a SBME curriculum was created, in a limited simulation resource setting at a 4-year Emergency Medicine (EM) residency program at the American University of Beirut Medical Center. METHODS: A case-based pilot simulation curriculum was developed following Kern's 6 step approach to curriculum design. The curricular objectives were identified through an anonymous survey of the program's residents and faculty. Curriculum outcomes were assessed, and the curriculum was revised to address curricular barriers. Evaluations of the revised curriculum were collected during the simulation sessions and through a whole revised curriculum evaluation at the end of the first year of its implementation. RESULTS: 14/20 residents (70%) and 8/8 faculty (100%) completed the needs assessment from which objectives for the pilot curriculum were developed and implemented through 6 2-h sessions over a 1-year period. Objectives were not met and identified barriers included cost, scheduling, resources, and limited faculty time. The revised curriculum addressed these barriers and 24 40-min sessions were successfully conducted during the following year. The sessions took place 3 at a time, in 2-h slots, using the same scenario to meet the objectives of the different learners' levels. 91/91 evaluations were collected from participants with overall positive results. The main differences between the pilot and the revised curricula included: a better understanding of the simulation center resources and faculty's capabilities. CONCLUSION: Simulation-based education is feasible even with limited-resources. However, understanding the resources available, and advocating for protected educator time are essential to implementing a successful EM simulation curriculum.

Opioid-Sparing Anesthetic Technique for Pediatric Patients Undergoing Adenoidectomy: A Pilot Study.

INTRODUCTION: An opioid-sparing anesthetic involves a multi-modal technique with non-opioid medications targeting different analgesic pathways. Such techniques may decrease adverse effects related to opioids. These techniques may be considered in patients at higher risk for opioid-related adverse effects including obstructive sleep apnea or sleep disordered breathing. METHODS: A prospective, pilot study was performed in 10 patients (3-8 years of age), presenting for adenoidectomy. The perioperative regimen included oral dextromethorphan (1 mg/kg) and acetaminophen (15 mg/kg) plus single boluses of intraoperative dexmedetomidine (0.5 µg/kg) and ketamine (0.5 mg/kg). Pain scores were assessed in the post anesthesia care unit (PACU) using the FLACC (Face, Legs, Activity, Cry, Consolability) scale. Patients with a pain score >4 received fentanyl as needed. PACU time, pain scores, and parent satisfaction were recorded. Postoperatively, patients were instructed to use oral acetaminophen or ibuprofen every 6 hours as needed for pain. RESULTS: The study cohort included 10 patients, 3-8 years of age. All patients had opioid-free anesthetic care. PACU time ranged from 24 to 102 minutes (median: 56 minutes). FLACC pain scores were 0 for all PACU assessments. Nine patients were discharged home and 1 patient had a planned overnight admission. Following hospital discharge, the pain scores were satisfactory during the 72-hour study period and 90% of the patients' guardians were satisfied or highly satisfied with their child's pain control. CONCLUSION: This opioid-sparing approach provided safe and effective pain control as well as parental satisfaction following adenoidectomy in children. Additional prospective studies are needed to determine whether this regimen is effective in a larger cohort of patients with and for other otolaryngology procedures.

An Interprofessional Approach in Caring for a Patient on Maintenance Hemodialysis with COVID-19 in Toronto, Canada: An Educational Case Report.

RATIONALE: Hemodialysis patients are at significant risk from COVID-19 due to their frequent interaction with the health care system and medical comorbidities. We followed up the trajectory of the first COVID-19-positive maintenance hemodialysis patient at Sunnybrook Health Sciences Centre in Toronto. We present the lessons learned and changes in practices that occurred to prevent an outbreak in our center. PRESENTING CONCERNS OF THE PATIENT: The patient, a 66-year-old woman on in-center hemodialysis, initially presented with a 2-day history of a productive cough. She subsequently developed a fever, was placed on contact and droplet isolation, and admitted to hospital. DIAGNOSES: On March 13, 2020, the patient tested positive for COVID-19. Within the next 48 hours, she developed hypoxia and acute respiratory distress syndrome as a complication of her illness requiring an extended critical care stay. This extended critical care stay resulted in critical illness-associated secondary sclerosing cholangitis. INTERVENTIONS: An interprofessional team was established, performing rapid Plan-Do-Study-Act quality improvement cycles to improve screening practices and promote the safety of patients and staff in the hemodialysis unit. OUTCOMES: We present here the lessons learned, the changes to our screening protocols, and the clinical course of our first in-center hemodialysis patient with SARS-CoV-2. TEACHING POINTS: Regular review of the infection screening processes is paramount in preventing outbreaks of COVID-19, particularly in hemodialysis units. Hospital admission should be arranged if a patient exhibits any clinical signs of hemodynamic compromise or hypoxia. Early education for health care practitioners caring for patients with COVID-19 and refresher information regarding personal protective equipment helped promote the safety of staff and prevent health care-associated outbreaks.

A Survey to Define and Predict Difficult Vascular Access in the Pediatric Perioperative Population.

BACKGROUND: Various criteria exist for defining difficult peripheral intravenous (DPIV) cannulation in infants and children. With the help of a survey tool, the characteristics perceived to increase the likelihood of DPIV cannulation amongst anesthesia providers were assessed. METHODS: An individualized survey regarding DPIV which included pediatric anesthesiology faculty and certified registered nurse anesthetists at Nationwide Children's Hospital and anesthesiology faculty members of Wake-up Safe was conducted. Anesthesia provider, patient, and procedural characteristics were expressed as a count and percentage, and compared according to group (faculty, certified registered nurse anesthetists, Wake-up Safe faculty) using analysis of variance. RESULTS: Of the 48 local respondents, 33 (69%) reported age as a contributing factor to DPIV, and 32 (67%) reported weight as a factor. Of the 22 Wake-up Safe respondents, 14 (63%) reported age, and 16 (73%) reported weight as a factor. Patient and procedural characteristics perceived to increased likelihood of DPIV cannulation did not differ by respondent role. The factors most commonly mentioned by local respondents as contributing to DPIV included trisomy 21, neuromuscular disorders, and history of many prior IV cannulations. Among the Wake-up Safe faculty respondents, the most commonly mentioned factors were neuromuscular disorders, trisomy 21, and skin injuries or conditions. CONCLUSION: Age and weight were the two most commonly reported factors from both groups of respondents. Other factors contributing to DPIV included prior history of DPIV, neuromuscular disorders, trisomy 21 and American Society of Anesthesiology status ≥4. Patient and procedural characteristics were perceived to increase the likelihood of DPIV cannulation with no difference among respondents.

Non-invasive carbon dioxide monitoring in patients with cystic fibrosis during general anesthesia: end-tidal versus transcutaneous techniques.

INTRODUCTION: The gold standard for measuring the partial pressure of carbon dioxide remains arterial blood gas (ABG) analysis. For patients with cystic fibrosis undergoing general anesthesia or polysomnography studies, continuous non-invasive carbon dioxide monitoring may be required. The current study compares end-tidal (ETCO2), transcutaneous (TCCO2), and capillary blood gas carbon dioxide (Cap-CO2) monitoring with the partial pressure of carbon dioxide (PaCO2) from an ABG in patients with cystic fibrosis. METHODS: Intraoperatively, a single CO2 value was simultaneously obtained using ABG (PaCO2), capillary (Cap-CO2), TCCO2, and ETCO2 techniques. Tests for correlation (Pearson's coefficient) and agreement (Bland-Altman analysis) were performed. Data were further stratified into two subgroups based on body mass index (BMI) and percent predicted forced expiratory volume in 1 s (FEV1%). Additionally, the absolute difference in the TCCO2, ETCO2, and Cap-CO2 values versus PaCO2 was calculated. The mean ± SD differences were compared using a paired t test while the number of times the values were ≤ 3 mmHg and ≤ 5 mmHg from the PaCO2 were compared using a Fishers' exact test. RESULTS: The study cohort included 47 patients (22 males, 47%) with a mean age of 13.4 ± 7.8 years, median (IQR) BMI of 18.7 kg/m2 (16.7, 21.4), and mean FEV1% of 87.3 ± 18.3%. Bias (SD) was 4.8 (5.7) mmHg with Cap-CO2 monitoring, 7.3 (9.7) mmHg with TCCO2 monitoring, and 9.7 (7.7) mmHg with ETCO2 monitoring. Although there was no difference between the degree of bias in the population as a whole, when divided based on FEV1% and BMI, there was greater bias with ETCO2 in patients with a lower FEV1% and a higher BMI. The Cap-CO2 vs. PaCO2 difference was 5.2 ± 5.3 mmHg (SD), with 16 (48%) ≤ 3 mmHg and 20 (61%) ≤ 5 mmHg from the ABG value. The TCCO2-PaCO2 difference was 9.1 ± 7.2 mmHg (SD), with 11 (27%) ≤ 3 mmHg and 15 (37%) ≤ 5 mmHg from the ABG value. The ETCO2-PaCO2 mean difference was 11.2 ± 7.9 mmHg (SD), with 5 (12%) ≤ 3 mmHg and 11 (26%) ≤ 5 mmHg from the ABG value. CONCLUSIONS: While Cap-CO2 most accurately reflects PaCO2 as measured on ABG, of the non-invasive continuous monitors, TCCO2 was a more accurate and reliable measure of PaCO2 than ETCO2, especially in patients with worsening pulmonary function (FEV1% ≤ 81%) and/or a higher BMI (≥ 18.7 kg/m2).

Evaluating Sufficient Similarity of Botanical Dietary Supplements: Combining Chemical and In Vitro Biological Data.

Botanical dietary supplements are complex mixtures with numerous potential sources of variation along the supply chain from raw plant material to the market. Approaches for determining sufficient similarity (ie, complex mixture read-across) may be required to extrapolate efficacy or safety data from a tested sample to other products containing the botanical ingredient(s) of interest. In this work, screening-level approaches for generating both chemical and biological-response profiles were used to evaluate the similarity of black cohosh (Actaea racemosa) and Echinacea purpurea samples to well-characterized National Toxicology Program (NTP) test articles. Data from nontargeted chemical analyses and gene expression of toxicologically important hepatic receptor pathways (aryl hydrocarbon receptor [AhR], constitutive androstane receptor [CAR], pregnane X receptor [PXR], farnesoid X receptor [FXR], and peroxisome proliferator-activated receptor alpha [PPARα]) in primary human hepatocyte cultures were used to determine similarity through hierarchical clustering. Although there were differences in chemical profiles across black cohosh samples, these differences were not reflected in the biological-response profiles. These findings highlight the complexity of biological-response dynamics that may not be reflected in chemical composition profiles. Thus, biological-response data could be used as the primary basis for determining similarity among black cohosh samples. Samples of E. purpurea displayed better correlation in similarity across chemical and biological-response measures. The general approaches described herein can be applied to complex mixtures with unidentified active constituents to determine when data from a tested mixture (eg, NTP test article) can be used for hazard identification of sufficiently similar mixtures, with the knowledge of toxicological targets informing assay selection when possible.

The Power of Resolution: Contextualized Understanding of Biological Responses to Liver Injury Chemicals Using High-throughput Transcriptomics and Benchmark Concentration Modeling.

Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions, however, limited throughput, high-costs, and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. To address these challenges, we have utilized a novel high-throughput transcriptomics (HTT) platform, TempO-Seq, to apply the interpretive power of concentration-response modeling with exposures to 24 reference compounds in both differentiated and non-differentiated human HepaRG cell cultures. Our goals were to (1) explore transcriptomic characteristics distinguishing liver injury compounds, (2) assess impacts of differentiation state of HepaRG cells on baseline and compound-induced responses (eg, metabolically-activated), and (3) identify and resolve reference biological-response pathways through benchmark concentration (BMC) modeling. Study data revealed the predictive utility of this approach to identify human liver injury compounds by their respective BMCs in relation to human internal exposure plasma concentrations, and effectively distinguished drug analogs with varied associations of human liver injury (eg, withdrawn therapeutics trovafloxacin and troglitazone). Impacts of cellular differentiation state (proliferated vs differentiated) were revealed on baseline drug metabolizing enzyme expression, hepatic receptor signaling, and responsiveness to metabolically-activated toxicants (eg, cyclophosphamide, benzo(a)pyrene, and aflatoxin B1). Finally, concentration-response modeling enabled efficient identification and resolution of plausibly-relevant biological-response pathways through their respective pathway-level BMCs. Taken together, these findings revealed HTT paired with differentiated in vitro liver models as an effective tool to model, explore, and interpret toxicological and pharmacological interactions.

Hemodynamic and pharmacokinetic analysis of oxymetazoline use during nasal surgery in children.

OBJECTIVES/HYPOTHESIS: Oxymetazoline is an α-adrenergic agonist that is commonly used as a topical hemostatic agent in the operating room during ear, nose, and throat surgery. There are limited data on oxymetazoline pharmacokinetics in children who undergo general anesthesia. We assessed the hemodynamic effects and systemic absorption of topically applied oxymetazoline in children undergoing various nasal procedures. STUDY DESIGN: Prospective trial. METHODS: Children ages 2 to 17 years undergoing functional endoscopic sinus surgery, turbinate resection, or adenoidectomy were enrolled. The surgeon placed oxymetazoline-soaked pledgets (1.5 mL of 0.05% solution) according to our usual clinical practice. Blood samples for oxymetazoline assay were drawn at 5, 10, 20, 45, 90, and 150 minutes, and hemodynamic data were recorded at 5-minute intervals. Data analysis included mixed-effects regression and population pharmacokinetic/pharmacodynamic modeling. RESULTS: The analysis included 27 patients, age 7 ± 4 years, who received between 2 and 12 pledgets (3-18 mL) of oxymetazoline. Relative bioavailability compared to the spray formulation was 2.3 (95% confidence interval [CI]: 1.6-3.2), with slow absorption from the mucosal surface (absorption half-life 64 minutes; 95% CI: 44-90). Mean arterial pressure did not increase with oxymetazoline instillation at the observed oxymetazoline serum concentrations (0.04-7.6 µg/L). CONCLUSIONS: Despite concerns regarding oxymetazoline administration to mucosal membranes, we found that hemodynamic changes were clinically negligible with our usual clinical use of pledgets soaked in oxymetazoline. Compared to data on oxymetazoline in spray formulation, bioavailability was increased twofold with pledgets, but systemic absorption was very slow, contributing to low serum concentrations and limited hemodynamic effects. LEVEL OF EVIDENCE: 1b. Laryngoscope, 129:2775-2781, 2019.

Perioperative Provider and Staff Competency in Providing Culturally Competent LGBTQ Healthcare in Pediatric Setting.

INTRODUCTION: Children and adolescents identifying as lesbian, gay, bisexual, transgender, or queer/questioning (LGBTQ) may feel reluctant to seek medical care due to stigma and the possibility of negative interactions with health care providers. Due to the short duration of the perioperative period, the interaction in this setting is limited and providers may not have the time to develop a rapport with the patient. It is imperative that staff are trained to address the patient and family in a culturally competent manner. METHODS: We undertook surveys before and after a 2 part educational series among the pediatric perioperative staff to understand the impact of providing education and cultural competency training regarding caring for patients who identify as LGBTQ. Providers self-reported their knowledge and comfort on a 1-5 point scale (5 being most knowledgeable or comfortable) in 6 domains of caring for LGBTQ patients. Objective knowledge of LGBTQ issues was assessed using 7 questions based on lecture material. On objective assessment, knowledge of LGBTQ issues improved after cultural competency training. RESULTS: The analysis included 90 responses. Before training, median ratings of knowledge and comfort were 3 or 4 out of a maximum of 5 for each domain. The pre-training median score on the 7-item test of LGBTQ cultural competency was 5 (IQR: 4, 6). After training, knowledge and comfort self-ratings did not improve, but the score on the objective knowledge test increased to a median of 6 (IQR: 4, 7; p=0.011) of 7 possible points. DISCUSSION: Anesthesia providers participating in LGBTQ cultural competency training self-reported high levels of knowledge and comfort with providing care to LGBTQ patients even before formal training was provided. On objective assessment, knowledge of LGBTQ issues improved after cultural competency training.

Analgesic effects of methadone and magnesium following posterior spinal fusion for idiopathic scoliosis in adolescents: a randomized controlled trial.

PURPOSE: To provide optimal conditions for neurophysiological monitoring and rapid awakening, remifentanil is commonly used during pediatric spinal surgery. However, remifentanil may induce hyperalgesia and increase postoperative opioid requirements. We evaluated the potential of methadone or magnesium to prevent remifentanil-induced hyperalgesia. METHODS: Using a prospective, randomized, blinded design, adolescents presenting for posterior spinal fusion to treat idiopathic scoliosis were assigned to receive desflurane with remifentanil alone (REMI), remifentanil + methadone (MET) (0.1 mg/kg IV over 15 min), or remifentanil + magnesium (MAG) (50 mg/kg bolus over 30 min followed by 10 mg/kg/h). Primary outcomes were opioid requirements and postoperative pain scores. Secondary outcomes included intraoperative anesthetic requirements, neurophysiological monitoring conditions, and emergence times. RESULTS: Data analysis included 60 patients. Total opioid requirement (hydromorphone) in the REMI group (received perioperatively and on the inpatient ward) was 0.34 ± 0.11 mg/kg compared to 0.26 ± 0.10 mg/kg in the MET group (95% confidence interval (CI) of difference: - 0.14, - 0.01; p = 0.035). The difference in opioid requirements between the REMI and MET group was related to intraoperative dosing (0.04 ± 0.02 mg/kg vs. 0.02 ± 0.01 mg/kg; 95% CI of difference: - 0.01, - 0.02; p = 0.003). No difference was noted in pain scores, and no differences were noted when comparing the REMI and MAG groups. CONCLUSION: With the dosing regimens in the current study, the only benefit noted with methadone was a decrease in perioperative opioid requirements. However, given the potential for hyperalgesia with the intraoperative use of remifentanil, adjunctive use of methadone appears warranted.

Optimizing Mastery Learning Environments: A New Approach to Deliberate Practice for Simulation-based Learning.

BACKGROUND: Deliberate practice (DP) is a method of mastery learning widely used in healthcare education. Investigations into improved mastery learning environments are important as we move to competency-based educational models. The objective of this pilot project is to create and test the feasibility of a simulation-based learning methodology based on close adherence to the tenants of DP for the acquisition of mastery knowledge. METHODS: We created a new methodology for simulation-based mastery learning modules after review of the tenants of DP. A module was constructed to highlight important aspects of supraventricular tachycardia (SVT) management in accordance with current American Heart Association practice guidelines and underwent expert review. Ten emergency medicine interns completed the module as part of the pilot. The number of case attempts, critical actions completed, and time to cardioversion of unstable patients were recorded. Resident confidence was reported before and several months after the module via survey instrument. RESULTS: Six cases of patients presenting with SVT were created and critical actions were defined. Cases were ordered in increasing difficulty to form a module in which learners were placed immediately into more complex contexts to practice the skill of SVT management with feedback provided between each case attempt. Residents averaged 2.5 attempts to complete case one. All completed case six on first attempt. All residents completed the six cases within the 2-hour module. Time to cardioversion decreased significantly on repetitive practice. Increased resident confidence in several areas of SVT management was maintained several months postintervention. CONCLUSION: The best methods for the use of DP to encourage mastery learning have not been well defined. Participation in our pilot case increased novice trainee performance and confidence in the management of SVT. Several challenges inherent in testing mastery knowledge acquisition were encountered and will inform future study of this new educational strategy.

Comprehensive Analyses and Prioritization of Tox21 10K Chemicals Affecting Mitochondrial Function by in-Depth Mechanistic Studies.

BACKGROUND: A central challenge in toxicity testing is the large number of chemicals in commerce that lack toxicological assessment. In response, the Tox21 program is re-focusing toxicity testing from animal studies to less expensive and higher throughput in vitro methods using target/pathway-specific, mechanism-driven assays. OBJECTIVES: Our objective was to use an in-depth mechanistic study approach to prioritize and characterize the chemicals affecting mitochondrial function. METHODS: We used a tiered testing approach to prioritize for more extensive testing 622 compounds identified from a primary, quantitative high-throughput screen of 8,300 unique small molecules, including drugs and industrial chemicals, as potential mitochondrial toxicants by their ability to significantly decrease the mitochondrial membrane potential (MMP). Based on results from secondary MMP assays in HepG2 cells and rat hepatocytes, 34 compounds were selected for testing in tertiary assays that included formation of reactive oxygen species (ROS), upregulation of p53 and nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), mitochondrial oxygen consumption, cellular Parkin translocation, and larval development and ATP status in the nematode Caenorhabditis elegans. RESULTS: A group of known mitochondrial complex inhibitors (e.g., rotenone) and uncouplers (e.g., chlorfenapyr), as well as potential novel complex inhibitors and uncouplers, were detected. From this study, we identified four not well-characterized potential mitochondrial toxicants (lasalocid, picoxystrobin, pinacyanol, and triclocarban) that merit additional in vivo characterization. CONCLUSIONS: The tier-based approach for identifying and mechanistically characterizing mitochondrial toxicants can potentially reduce animal use in toxicological testing. https://doi.org/10.1289/EHP2589.

A Standardized Needs Assessment Tool to Inform the Curriculum Development Process for Pediatric Resuscitation Simulation-Based Education in Resource-Limited Settings.

INTRODUCTION: Under five mortality rates (UFMR) remain high for children in low- and middle-income countries (LMICs) in the developing world. Education for practitioners in these environments is a key factor to improve outcomes that will address United Nations Sustainable Development Goals 3 and 10 (good health and well being and reduced inequalities). In order to appropriately contextualize a curriculum using simulation, it is necessary to first conduct a needs assessment of the target learner population. The World Health Organization (WHO) has published a tool to assess capacity for emergency and surgical care in LMICs that is adaptable to this goal. MATERIALS AND METHODS: The WHO Tool for Situational Analysis to Assess Emergency and Essential Surgical Care was modified to assess pediatric resuscitation capacity in clinical settings in two LMICs: Uganda and Myanmar. Modifications included assessment of self-identified learning needs, current practices, and perceived epidemiology of disease burden in each clinical setting, in addition to assessment of pediatric resuscitation capacity in regard to infrastructure, procedures, equipment, and supplies. The modified tool was administered to 94 respondents from the two settings who were target learners of a proposed simulation-based curriculum in pediatric and neonatal resuscitation. RESULTS: Infectious diseases (respiratory illnesses and diarrheal disease) were cited as the most common causes of pediatric deaths in both countries. Self-identified learning needs included knowledge and skill development in pediatric airway/breathing topics, as well as general resuscitation topics such as CPR and fluid resuscitation in shock. Equipment and supply availability varied substantially between settings, and critical shortages were identified in each setting. Current practices and procedures were often limited by equipment availability or infrastructural considerations. DISCUSSION AND CONCLUSION: Epidemiology of disease burden reported by respondents was relatively consistent with WHO country-specific UFMR statistics in each setting. Results of the needs assessment survey were subsequently used to refine goals and objectives for the simulation curriculum and to ensure delivery of pragmatic educational content with recommendations that were contextualized for local capacity and resource availability. Effective use of the tool in two different settings increases its potential generalizability.

Current perioperative care of infants with pyloric stenosis: comparison of survey results.

BACKGROUND: Considerable variation in the perioperative management of infants with pyloric stenosis (PS) led the authors to undertake a survey of pediatric anesthesiologists to determine if consensus-based guidelines could be developed. MATERIALS AND METHODS: Physicians who are members of the Society for Pediatric Anesthesia or the Association of Pediatric Anaesthetists of Great Britain and Ireland completed an online questionnaire through SurveyMonkey regarding current management of patients with PS. RESULTS: There were significant differences in the use of anticholinergic premedication, the selection of induction technique, and the use of adjuvant regional analgesia between the members of both organizations. CONCLUSIONS: The authors recommend creating an international multiinstitutional registry to prospectively record and track perioperative management of patients with PS to facilitate the development of clinical practice guidelines.