Use of a SimBox, a Video-Augmented, Newborn Resuscitation Simulation for Prehospital Providers to Measure Clinical Performance and Educational Experience.

OBJECTIVES: Few studies have described the current clinical practices, adherence to guidelines, and outcomes of newborn resuscitations attended by emergency medical services (EMS). SimBox, a novel, video-augmented simulation, was used to describe the adherence of prehospital providers to Neonatal Resuscitation Program guidelines, to measure satisfaction with the simulation intervention, and to describe the self-reported improvement in knowledge, skills, and attitudes after the simulation. METHODS: A prospective observational cohort study of EMS providers was designed and conducted using SimBox, an open-access simulation platform, and facilitated by EMS educators. Clinical performance measures were collected using a five-item checklist. Simulation satisfaction measures were collected through net promoter scores. Learners' demographics, and self-reported knowledge, skills, and attitudes were measured using a retrospective survey of 25 questions. RESULTS: In total, 33 facilitator and 55 learner surveys were collected across Connecticut, Colorado, and Alaska between July 2021 and September 2022. At least one deviation from clinical guidelines occurred in 22/30 (73.3%) of the sessions, with 10/30 (33.3%) teams inappropriately performing chest compressions, 5/31 (16.1%) teams not warming, drying, stimulating, and suctioning the newborn, and 7/31 (22.6%) teams not performing positive pressure ventilation correctly. Lastly, 10/30 (33.3%) teams administered an incorrect dose of dextrose-containing fluids. Very high levels of satisfaction were reported with net promoter scores of 97 and 82 out of 100 for the facilitator and learner surveys, respectively. Finally, all 55/55 (100%) of the learners strongly or somewhat agreed that the simulation improved their knowledge, teamwork, communication, and psychomotor skills. CONCLUSIONS: In this cohort of prehospital providers, clinical management decisions during a newborn resuscitation simulation often deviated from the gold-standard, newborn resuscitation guidelines. Free, online, open-access simulation resources like SimBox can be used to identify and measure practice deviations from standardized resuscitation protocols in the prehospital setting.

Variation in the Guidelines for the Acute Management of Anaphylaxis in Pediatric Patients: An International Narrative Review.

OBJECTIVES: Evidence-based guidelines have been created and disseminated by multiple organizations to standardize the care of pediatric patients with anaphylaxis. Differences across these guidelines can cause confusion and potentially errors in clinical practice leading to patient harm. The aim of this study was to describe and identify patterns of variation in the current guidelines. METHODS: A narrative review with 3 major components was designed. First, a narrative review of current, peer-reviewed, guidelines published by national and international allergy and immunology, pediatric, and emergency medicine organizations was performed. That was followed by a gray literature review of guidelines by resuscitation councils and national health organizations. The third component focused on the translation of these guidelines at local and institutional levels by reviewing clinical pathways published by academic institutions. RESULTS: With regard to the fixed epinephrine autoinjector dosing, 50% (6 of 12) of the reviewed guidelines offered weight-based and 41.7% (5 of 12) age-based dosing recommendations. Furthermore, different weight cutoffs for the 0.15- and 0.3-mg autoinjectors were identified among guidelines. Variation was identified in the description of intramuscular epinephrine concentration ("1:1000," "1 mg/mL," or both), the recommended concentration for intravenous administration ("1:10,000" or "1:1000"), or the rate of infusion or titration. Eight of the 12 guidelines (66.7%) recommend a dose in milligrams, and 33.3% (4 of 12) in micrograms. Five of 12 (41.7%) used both milliliters and milligrams or micrograms. CONCLUSIONS: Notable variation in the current guidelines for the acute management of anaphylaxis in the pediatric population was identified. Flagging this variability could help inform a consensus-based approach toward harmonization of guidelines, which in turn could streamline the management of anaphylaxis in pediatric patients across the United States, Canada, Ireland, the United Kingdom, Europe, Australia, and New Zealand, and hopefully prevent errors and mitigate patient harm.

Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation.

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors.

BACKGROUND: Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk. SUBJECTS, MATERIALS, AND METHODS: This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at diagnosis ≤19 years, survival ≥5 years) were followed up over a median time period of 12.3 (5-40.9) years. Independent predictors of cardiovascular mortality (CVM) were combined into a risk score, which was developed in a derivation set (n = 22,374), and validated in separate patient registries (n = 6,437). RESULTS: In the derivation registries, older age at diagnosis (≥10 years vs. reference group of 1-5 years), male sex, non-white race, a history of lymphoma, and a history of radiation were independently associated with an increased risk of CVM among long-term CCS (p < .05). A risk score derived from this model (Childhood and Adolescence Cancer Survivor CardioVascular score [CHACS-CV], range: 0-8) showed good discrimination for CVM (Harrell's C-index [95% confidence interval (CI)]: 0.73 [0.68-0.78], p < .001) and identified a high-risk group (CHACS-CV ≥6), with cumulative CVM incidence over 30 years of 6.0% (95% CI: 4.3%-8.1%) versus 2.6% (95% CI: 1.8%-3.7%), and 0.7% (95% CI: 0.5%-1.0%) in the mid- (CHACS-CV = 4-5) and low-risk groups (CHACS-CV ≤3), respectively (plog-rank < .001). In the validation set, the respective cumulative incidence rates were 4.7%, 3.1%, and 0.8% (plog-rank < .001). CONCLUSION: We propose a simple risk score that can be applied in everyday clinical practice to identify long-term CCS at increased cardiovascular risk, who may benefit from early cardiovascular screening, and risk-reduction strategies. IMPLICATIONS FOR PRACTICE: Childhood cancer survivors (CCS) are known to be at increased cardiovascular risk. Currently available prognostic tools focus on treatment-related adverse events and late development of congestive heart failure, but there is no prognostic model to date to estimate the risk of cardiovascular mortality among long-term CCS. A simple clinical tool is proposed for cardiovascular risk stratification of long-term CCS based on easily obtainable information from their medical history. This scoring system may be used as a first-line screening tool to assist health care providers in identifying those who may benefit from closer follow-up and enable timely deployment of preventive strategies.

Cloning and characterization of the trout perforin.

The pore-forming protein, perforin is one of the effectors of cell-mediated killing. A perforin cDNA clone was isolated from rainbow trout (Oncorhynchus mykiss) after screening of a spleen cDNA library. The full-length cDNA is 2070 bp in size, encoding for a polypeptide of 589 amino acids. The predicted amino acid sequence of the trout perforin is 64, 58 and 40% identical to those of Japanese flounder, zebrafish and human perforins, respectively. Although its membrane attack complex/perforin (MACPF) domain is conserved, trout perforin shows low homology to human and trout terminal complement components (C6, C7, C8 and C9), ranging from 19 to 26% identity. Expression analysis reveals that the trout perforin gene is expressed in the blood, brain, heart, kidney, intestine and spleen. Phylogenetic analysis of proteins which belong to the MACPF superfamily clusters the trout perforin in the same group with other known perforins.