Rapid decay of transthoracic echocardiography skills at 1 month: A prospective observational study.

OBJECTIVE: Focused transthoracic echocardiography (FTTE) is an emerging tool in the management of critically ill patients, but the lack of adequate training models has limited the expansion of this technology. Although basic FTTE training courses have been shown to be sufficient in developing echocardiography skills, limited data exist regarding skill retention. In an effort to develop an adequate FTTE training model, we sought to determine the degree of skill retention after FTTE training. DESIGN: A prospective, observational study. SETTING: An academic center. PARTICIPANTS: Surgical residents and medical students: 31 subjects were enrolled from February to June 2016. RESULTS: Participants underwent a 2-hour FTTE course including didactics and a hands-on session measuring ejection fraction of left ventricle (LV) and inferior vena cava (IVC) diameter. Written knowledge and performance examinations applying FTTE were conducted before the course, immediately after, and at 1- and 3-month intervals, which were evaluated on a 0 to 9 scale and analyzed with paired t-tests. Performance examination scores obtaining the LV and IVC views preinitial and postinitial training increased from 1.7 to 6.5 (LV) and from 2.0 to 6.8 (IVC) (p < 0.01), decreased to 5.0 and 4.8, respectively, at 1 month (posttraining vs 1 month, p < 0.01), and did not significantly change at 3 months (5.4 and 5.0, respectively). Written examination scores increased from 42% to 62% (pretraining vs posttraining, p < 0.01), decreased to 48% in 1 month (posttraining vs 1 month, p < 0.01), and further decreased to 34% at 3 months (1 month vs 3 month, p < 0.01). CONCLUSIONS: Although a short training course appears sufficient to impart basic FTTE skills and knowledge, skills are significantly decayed at 1 month and knowledge continually decreases at 1 and 3 months. Future FTTE training models should consider the rapid degradation of knowledge and skills in determining frequency of refresher training and ongoing evaluation.

Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial.

BACKGROUND: US government organisations have identified the need for a new smallpox vaccine to replenish limited stocks of the approved, calf-lymph derived vaccine, the manufacture of which is no longer acceptable. We aimed to compare the safety and immunogenicity of the new cell-cultured smallpox vaccine (CCSV) to that of the calf-lymph derived vaccine (as a positive control) in 350 healthy, adult volunteers. METHODS: We did a randomised controlled study at the University of Kentucky Medical Center. We randomised 150 vaccinia-naive volunteers, aged 18-30 years, and 100 vaccinia-non-naive people, aged 32-65 years, to equivalent doses of either CCSV or test vaccine (2.5x10(5) plaque-forming units) by 15 puncture scarification in double-blind fashion. Immunogenicity was assessed by pock formation (take rate), humoral immune response by plaque-reduction neutralisation titres, and cellular immune response by vaccinia-specific, interferon-gamma T-cell quantification, cytotoxicity, and T-cell proliferation response. A further 100 vaccine-naive individuals, aged 18-30 years, received one of five doses of CCSV (undiluted, diluted 1 in 5, 1 in 10, 1 in 25, and 1 in 50) in single-blind fashion. Routine laboratory assessments, physical examinations, and recording of adverse events were done to assess vaccine safety. The primary endpoints were safety and reactogenicity (take rate) of CCSV. FINDINGS: 349 (99.7%) of 350 volunteers developed pock lesions; one vaccinia-naive individual who received a 1 in 25 dilution of CCSV did not. The rate of adverse events related to vaccine and the extent of humoral and cellular immune responses did not differ between the vaccine groups in vaccinia-naive or non-naive people. CCSV was immunogenic in vaccine-naive volunteers at a dose 50 times lower than that approved for Dryvax. INTERPRETATION: CCSV seems to be a safe and immunogenic alternative to calf-lymph derived vaccine for both vaccinia-naive and non-naive people.

Development of a novel vaccinia-neutralization assay based on reporter-gene expression.

In anticipation of large-scale smallpox vaccination, clinical trials of new vaccine candidates with improved safety profiles, and new vaccinia immune globulin (VIG) products, there is an immediate need to develop new assays to measure vaccinia-specific immune responses. The classical assay to measure vaccinia neutralization, the plaque-reduction neutralization test (PRNT), is slow, labor intensive, and difficult to validate and transfer. Here we describe the development of a novel vaccinia-neutralization assay based on the expression of a reporter gene, beta-galactosidase (beta-Gal). Using a previously constructed vaccinia-beta-Gal recombinant virus, vSC56, we developed a neutralization assay that is rapid, sensitive, and reproducible. The readout is automated. We show that the neutralizing titers, ID(50), for several VIG products measured by our assay were similar to those obtained by PRNTs. A new Food and Drug Administration VIG standard was established for distribution to other laboratories. The new assay will serve as an important tool both for preclinical and clinical trials of new smallpox vaccines and for evaluation of therapeutic agents to treat vaccine-associated adverse reactions.