Reproducibility of Symptom Sequences Across Episodes of Recurrent Anaphylaxis.

BACKGROUND: Anaphylactic reactions may present with varying levels of severity, ranging from mild multisystem involvement to severe, and sometimes fatal, anaphylaxis. The severity of anaphylaxis is variable from one reaction to the next within the same individuals. OBJECTIVE: To compare the temporal sequence of symptoms within individuals and between individuals across multiple anaphylactic reactions. METHODS: Patients were evaluated for recurrent anaphylaxis in a tertiary care allergy clinic between 2012 and 2018. At each visit, patients were asked to record the temporal sequence in which symptoms of anaphylaxis appeared. These data were recorded at each visit and retrieved through retrospective chart review. Patients with a history of ≥2 anaphylactic reactions were included; those with anaphylaxis due to multiple allergens were excluded. The Fleiss Kappa method was used to assess reproducibility of the order of appearance of specific symptoms during anaphylaxis within individual patients and between individuals with similar triggers. RESULTS: The mean patient age was 35.6 years (standard deviation = 13.9; range: 1-68 years); 113 of 149 (76%) patients were female. The mean Fleiss Kappa reproducibility score within individuals was 0.94, 5th percentile was 0.53, and 95th percentile was 1.0. The mean Kappa score between individuals was -0.03 (range, -0.14 to 0.05). Among the 16 of 149 patients who recorded reactions of varying severity grades, the mean within-patient Kappa score was 0.96. CONCLUSION: Individual patients experience reproducibly stereotypic anaphylactic reactions over time, which are unique to a given patient, irrespective of the cause of anaphylaxis, including foods, medications, mast cell disorders, and idiopathic anaphylaxis. In contrast, symptom sequences during anaphylaxis are not reproducible between individuals.

Hemodynamic Aspects of Veno-Arterial Extracorporeal Membrane Oxygenation for Cardiac Support: A Worldwide Survey.

There is limited data available to guide management of patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). An international cross-sectional survey of medical directors/program coordinators from Extracorporeal Life Support Organization centers was conducted. A hierarchical clustering on principle components was used. A total of 243 (55%) centers responded and were divided into three clusters: Cluster 1 (n = 102) had few high volumes and low specialized heart failure (HF) involvement; Cluster 2 (n = 75) had few high volumes and moderate HF involvement; Cluster 3 (n = 66) contained the majority of centers with >50 annual cases and high HF involvement. The most divergent responses were observed between Clusters 1 and 3 wherein Cluster 1 centers were less likely to change management based on pulse pressure (77% vs. 100%; p < 0.001) and would rather avoid inotropes to "rest the heart" (28%). Cluster 3 centers were more likely to perform daily echocardiograms (50% vs. 24%, p < 0.001), which were less likely to be exclusively performed by cardiologist (36% vs. 58%, p < 0.046) and base weaning on echocardiographic findings, when compared to Cluster 1 (3.97/5 vs. 3.56, p < 0.001). Responses were variable in management reflecting the lack of evidence for hemodynamic care for those supported with VA-ECMO.

Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.