Prehospital Evaluation of the FAST-ED as a Secondary Stroke Screen to Identify Large Vessel Occlusion Strokes.

Introduction: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) was developed to identify Large Vessel Occlusion Strokes (LVOS) presenting out of hospital, although there is limited prospective research validating its use in this setting. This study evaluated the test characteristics of the FAST-ED to identify LVOS when used as a secondary stroke screen in the prehospital environment. Secondary analysis compared the performance of the CPSS and the FAST-ED in identifying an LVOS. Methods: This prospective, observational study was conducted from April 2018 to December 2019 in a municipal EMS system with all ALS ambulance response. The FAST-ED was implemented as a secondary screening tool for emergent stroke patients who had at least one positive Cincinnati Prehospital Stroke Screen (CPSS) item. CPSS and FAST-ED scores were extracted from prehospital electronic care reports, while the presence of LVOS was extracted from hospital records. Results: A total 1,359 patients were enrolled; 55.3% female, 47.5% white, with a mean age of 69.4 (SD 15.8). In this cohort, 11.3% of patients experienced an LVOS. The mean FAST-ED for a patient experiencing an LVOS was 5.33 (95%CI 4.97-5.69) compared to 3.06 (95%CI 2.95-3.12) (p < 0.001). A score of greater or equal to 4 yielded the highest combination of sensitivity (77.78%) and specificity (65.34%) with positive likelihood ratio 2.24 (95% CI 2.00-2.52) and negative likelihood ratio 0.34 (95% CI 0.25-0.46). Area under the ROC curve was 0.77 (95%CI 0.73, 0.81). A CPSS with all three items positive demonstrated a sensitivity of 73.20% and 69.57% specificity, with an ROC area of 0.73 (95% CI 0.70-0.77). When comparing a FAST-ED ≥4 to a CPSS of all positive items, there was no significant difference in sensitivity (p > 0.05), and the FAST-ED had a significantly lower specificity than the CPSS (p < 0.005). Conclusion: As stroke care advances, EMS agencies must consider their destination triage needs. This study suggests agencies must consider the use of single versus secondary scales, and to determine the ideal sensitivity and specificity for their system.

Inter-Rater Reliability of the FAST-ED in the Out-of-Hospital Setting.

Introduction: Patients experiencing a large vessel occlusion stroke (LVOS) may require endovascular-capable centers and benefit from direct transport to such facilities, creating a need for an accurate prehospital assessment. The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) is a secondary scale to identify LVOS. Currently, there is limited prospective evidence validating the use of the FAST-ED in the prehospital environment. This study aimed to evaluate the inter-rater reliability of the FAST-ED between patient care providers in the prehospital setting.Methods: This prospective study was conducted between 4/1/2018 and 7/1/2018 in a single municipal EMS agency that staffs two providers per ambulance with at least one being a paramedic. Patients were included based on paramedic impression that the patient was both having a stroke and greater than 18 years old. Each provider independently performed and documented a FAST-ED assessment on eligible patients. Data analysis consisted of performing inter-rater reliability using Cohen's Kappa on the FAST-ED score between primary and secondary providers. The FAST-ED was analyzed on an item level, an aggregate level (cumulative of all items), and using the defined cut point of ≥4. A sub-analysis determined if inter-rater reliability changed across provider certification.Results: There were 231 patients included in this analysis with an average age of 68.5 years and 135 (58.4%) female. Inter-rater reliability varied across individual items in the scale from 90.1% agreement to 82.5%. When analyzing inter-rater reliability of the aggregate FAST-ED score, the scale demonstrated 70.1% agreement (Kappa 0.66), considered substantial agreement. FAST-ED scores were analyzed using a cut point of ≥4. When using this cut point, there was 92.2% (Kappa 0.81) agreement between primary and secondary caregiver, demonstrating almost perfect agreement. Agreement was substantial across provider certifications including paramedics and EMTS.Conclusion: This study demonstrated high inter-rater reliability of the FAST-ED scale when performed in the prehospital setting on patients suspected of having a stroke. There were minimal differences in reliability based on provider certification, and item level analysis indicated substantial inter-rater reliability.

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine.

Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

Association of neighborhood characteristics with incidence of out-of-hospital cardiac arrest and rates of bystander-initiated CPR: implications for community-based education intervention.

OBJECTIVE: A 10-fold regional variation in survival after out-of-hospital cardiac arrest (OHCA) has been reported in the United States, which partly relates to variability in bystander cardiopulmonary resuscitation (CPR) rates. In order for resources to be focused on areas of greatest need, we conducted a geospatial analysis of variation of CPR rates. METHODS: Using 2010-2011 data from Durham, Mecklenburg, and Wake counties in North Carolina participating in the Cardiac Arrest Registry to Enhance Survival (CARES) program, we included all patients with OHCA for whom resuscitation was attempted. Geocoded data and logistic regression modeling were used to assess incidence of OHCA and patterns of bystander CPR according to census tracts and factors associated herewith. RESULTS: In total, 1466 patients were included (median age, 65 years [interquartile range 25]; 63.4% men). Bystander CPR by a layperson was initiated in 37.9% of these patients. High-incidence OHCA areas were characterized partly by higher population densities and higher percentages of black race as well as lower levels of education and income. Low rates of bystander CPR were associated with population composition (percent black: OR, 3.73; 95% CI, 2.00-6.97 per 1% increment in black patients; percent elderly: 3.25; 1.41-7.48 per 1% increment in elderly patients; percent living in poverty: 1.77, 1.16-2.71 per 1% increase in patients living in poverty). CONCLUSIONS: In 3 counties in North Carolina, areas with low rates of bystander CPR can be identified using geospatial data, and education efforts can be targeted to improve recognition of cardiac arrest and to augment bystander CPR rates.

Analysis of polyamidoamine dendrimers by isoelectric focusing.

Polyamidoamine dendrimers have been studied extensively for their potential applications in nanomedicine. Their uses as imaging, drug, and nucleic acid delivery agents are nearing clinical trials. As such, characterization of polyamidoamine dendrimers and their nano-devices is of immense importance for monitoring the efficiency of their synthesis, purity, and quality control of manufactured products as well as their in vivo behavior. We report here the analysis of polyamidoamine dendrimers possessing various cores and surface groups with a simple and inexpensive isoelectric focusing method. The isoelectric points of the dendrimers were readily determined from a calibration plot generated by running proteins with known pI values. The isoelectric points for various surface-modified polyamidoamine dendrimers ranged from 4 to 9. Polyamidoamine dendrimers possessing terminal hydroxyl groups gave a pI > 7, while those with terminal carboxyl groups exhibit a pI < 7. Generation number and cores of the dendrimers did not significantly affect their isoelectric points. Isoelectric focusing thus offers another important tool for characterizing these nanomolecules.

Preparation of fullerene-shell dendrimer-core nanoconjugates.

Generation 4 amine-terminated polyamidoamine dendrimer (PAMAM G4) was allowed to react with an excess of buckminsterfullerene (C60) to form a nanoconjugate containing a PAMAM core and C60 shell. The PAMAM-C60 conjugate was characterized by MALDI-TOF, TGA, UV-vis, and IR spectroscopy. Approximately thirty shell fullerenes surround each dendrimer core. The conjugates catalyze photooxidation of thioanisole by generation of singlet oxygen (1O2). The oxidation reactions occur in both organic and aqueous solvents, but the reactivity is enhanced in aqueous solution, possibly due to a nanoreactor effect resulting from diffusion of hydrophobic reactant molecules into dendrimer cavities.

Partial shell-filled core-shell tecto(dendrimers): a strategy to surface differentiated nano-clefts and cusps.

Poly(amidoamine) (PAMAM) dendrimer shell reagents possessing either nucleophilic (i.e., primary amines) or electrophilic (i.e., carboxymethyl esters) functional groups have been covalently assembled around appropriate electrophilic or nucleophilic dendrimer core reagents to produce partial shell filled/core-shell tecto(dendrimers). Partial shell-filled products with saturation levels ranging from 28% to 66% were obtained. These metastable, remarkably monodispersed assemblies possess functionally differentiated nano-cusps and clefts that exhibit "autoreactive" behavior. Pacification of these autoreactive products with appropriate alkanolamine reagents produced robust, nonreactive, "hydroxy-amine-differentiated" surfaces that exhibit very active self-assembly properties. Based on the monodispersity, dimensional scaling, and electrophoretic similarities of PAMAM dendrimers to globular proteins, these assemblies may be viewed as crude biomimetics of classical core shell-type protein aggregates. These dimensionally larger, but analogous PAMAM core-shell tecto(dendrimer) architectures extend and complete a similar pattern of autoreactivity and pacification that was observed earlier for traditional mono PAMAM dendrimer core-shell modules possessing unsaturated shell levels.