Mucosal rAd5 Immunization against SARS-CoV-2 Spike Elicits Cross-Reactive Nasal and Serum Neutralizing Antibodies and Protects Against Beta Variant Challenge in African Green Monkeys

Background. Mucosal vaccination may offer increased protection against SARS-CoV-2 compared to parental immunization. Here, we describe immunogenicity and efficacy following viral challenge in non-human primates after intranasal delivery of three unique non-replicating adenoviral vector vaccine (rAd5) candidates. Methods. African green monkeys (AMG) were prime boost immunized 29 days apart with vaccine candidates either expressing the parental spike protein alone (Wuhan-S), spike plus nucleocapsid(Wuhan-S-N), or the spike protein fromthe beta variant (beta-S). Serumand nasal swabs were collected every 14 days and humoral responses to full length spike (S) and receptor binding domain (RBD) were assessed.AllAMGs were challenged with SARS-CoV-2 B.1.351 (beta variant)onday 56. Viral loadsmeasured every two days by TCID50 in nasal washes and bronchial lavage fluid post challenge. Results. Mucosal immunization with Wuhan-S induced significant increases in serum IgG and IgA responses against the homologous parental lineage, as well as beta, delta, and omicron variants. In nasal samples, Wuhan-S immunization elicited over 500-fold increases in in cross-reactive IgA against multiple variants of concern including delta and omicron. While the beta-S rAd5 vaccine candidate induced enhanced serum IgG responses to homologous S and RBD proteins, this approach resulted in less cross-reactive antibodies to other variants compared to Wuhan-S rAd5 vaccine. Despite the differences in the ability to elicit cross-reactive antibody responses, all vaccinated AMGs challenged with SARS-CoV-2 B.1.351 (beta variant), had a significant reduction in viral titers by TCID50 in the nasal passages and reduced viral load in bronchial lavage fluid compared to unvaccinated controls. Conclusion. These results demonstrate mucosal administration of rAd5 clinical candidate vaccine, Wuhan-S, is immunogenic and offers cross-protective humoral responses in both serum and nasal compartments against a mismatched SARS-CoV-2 challenge virus.

The Impact of 'Golden Local Anaesthetic (GLA)' Principal on Emergency Theatre Efficiency - Analysing 232 Hand and Plastic Trauma Operations

Aim: 'Golden local anaesthetic' (GLA) principals are known to improve theatre efficiency. This first GLA case should be suitable to be completed unsupervised by a registrar and confirmed 12 hours prior to the start of the list with a negative COVID PCR test. This allows for list to be started, whilst the consultant is able to see and consent the remainder of the patients for that list, maximising theatre efficiency. Method: Operative timings was gathered in real time in our electronic database (TIMS). Initially, retrospective analysis was performed for cases in November 2020, comparing lists whereby a potential GLA first case was present, versus lists that did not. After remodelling this process, lists in October 2021 were analysed. Statistical analysis was carried out using Mann Whitney U Test. Results: Initially (PDSA-1), 110 trauma cases (58% GA and 42% LA) were performed [3.67/day] whilst post refinement (PDSA-2) 122 cases (52% GA and 48% LA) were performed [3.94 /day]. In PDSA-2, there was a 29% (9/ 31) uptake of GLA list principals. The average GLA list start time was 09:27hrs in PDSA-1 and 09:08hrs in PDSA-2 [Δ 19 mins, p<0.05] whilst the average non-GLA list start time was worse (09:53hrs and 10:12hrs). By refining the GLA principal, £470.63 was 'saved' with a further £445.86 potentially able to be saved when starting at the earliest recorded start time (1) Conclusions: The GLA model is a simple and sustainable method to improve theatre efficiency which could be adopted by other units.

Factors Associated with Successful Implementation of Worksite Mindfulness Interventions for Acute Care Nurses

Methods: A multi-phase, sequential, mixed-methods design explored critical aspects of the implementation process for worksite mindfulness-based interventions targeted to clinician groups that included acute care nurses working in academic medical centers. A descriptive, crosssectional survey design was used to obtain information related to variations in worksite mindfulness interventions and implementation processes acrossmultiple U.S. healthcare systems. Factors associated with implementation success were computed using regression analysis. Semi-structured interviews were completed to further explore, evaluate, and clarify strategies that have led to successful implementation and describe intervention, healthcare setting, or process-related barriers to implementation success. Results: Significant predictors of implementation success within academic healthcare systems included offering adapted mindfulness programming (p=.038) and paid time (p=.029) to support employee participation. Of these two predictors, offering paid time for employee participation provided the most significant (p=.008) contribution to organizational implementation success and was validated qualitatively by organizational implementation leaders. Background: Effects of nurse stress and burnout on work engagement, absenteeism, and turnover are well documented as are associations with medication errors and lapses in care. Mindfulness-based interventions are widely recognized for reducing employee stress and improving coping and resilience. However, mechanisms of success and sustainability are difficult to ascertain due to multiple inter-related factors including intervention features, nurse characteristics, and complexities of healthcare environments. The purpose of this study was to determine contextual factors contributing to implementation success of worksite mindfulness-based interventions aimed at supporting nurse health and wellbeing. Conclusion: An understanding of how and why specific development and implementation strategies for mindfulnessbased interventions are successful for nurses may be applicable to other interventions and more broadly to all healthcare professionals in the acute care healthcare environment. This is also valuable information for healthcare organizations that employ interventions targeted to employee well-being, especially considering the significant psychological impact of the COVID-19 pandemic on front line healthcare providers.

Oral Tablet Vaccination Induces Heightened Cross-Reactive CD8 T Cell Responses to SARS-COV-2 in Humans

Background. Covid-19 has accelerated global demand for easily distributed vaccines. Furthermore, as variant SARS-CoV-2 strains that circumvent antibody responses emerge, cross-protective vaccines provide substantial public health benefits. Vaxart is developing a shelf stable oral tablet vaccine that incorporates both the spike (S) and the more conserved nucleocapsid (N) proteins. Vaxart's vaccine platform uses a non-replicating adenovirus and a TLR3 agonist as an adjuvant. Methods. In an open-label phase 1 clinical study, 35 healthy subjects received either a single low (1x1010 IU;n=15) or high (5x1010 IU;n=15) dose of the vaccine candidate VXA-CoV2-1 with a small cohort receiving 2 low doses. PBMCs were taken at pre- and 7 days post-vaccination and restimulated with S and N peptides from SARSCoV-2 or the 4 human endemic coronaviruses (HCoV). Cells were stained for CD4/ CD8/CD107a (surface) and IFNγ/TNFα (intracellular). Subjects that received an intramuscular (i.m.) mRNA vaccine had PBMCs taken at the same timepoints and were compared in the same assay. Results. The study's results indicate that the VXA-CoV2-1 tablet was well tolerated. The majority of subjects had an increase in S-specific anti-viral CD8+ T cell responses. 19/26 (73%) subjects had a measurable CD8+ T cell response on day 8 above baseline, on average 1.5-4.6%. In a comparator experiment with the 2 SARS-CoV-2 i.m. mRNA vaccines, VXA-CoV2-1 outperformed other vaccine candidates with a >3.5-fold increase in S specific antiviral CD8 T cell responses. T cell responses specific to the 4 endemic HCoV were increased by 0.6% in subjects given VXA-CoV2-1. Conclusion. Here we describe a room temperature stable tablet that induces SARS-CoV-2 S specific CD8 T cells of high magnitude after one dose in humans. Overall, the level of antiviral SARS-CoV-2 specific T cells, particularly IFNg-producing CD8s, induced following oral immunization with VXA-CoV2-1 are of higher magnitude than the mRNA vaccines currently in use against COVID-19. T cell responses against 4 endemic HCoV were also induced. Because T cells may be important in protecting against death and severe infection, these results suggest that VXA-CoV2-1 could be cross-protective against a wide array of emerging pandemic coronaviruses.

In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray

Background: Nasal disinfection with 0.5% povidone-iodine (PVP-I) may be a useful adjunct in the management of COVID-19. The purpose of this article is to confirm the in vitro activity of the PVP-I nasal spray against SARS-CoV-2 and whether that may translate into reduced nasal shedding in vivo. Methods: Two SARS-CoV-2 virus isolates were exposed to 0.5% PVP-nasal spray (Nasodine®) for different times in vitro, with PCR and cell culture used to assess impact on viral infectivity and RNA copies. An open label in vivo single arm pilot study of 14 subjects with positive COVID-19 PCR diagnosis was undertaken. Baseline nasal swabs were collected to quantify SARS-CoV-2 pre-treatment, followed by a single 0.5% PVP nasal spray application (1.12 mL). Nasal swabs were collected at 5, 15, and 60 minutes post-dose to assess immediate and residual impact of treatment. Results: In vitro, the nasal spray reduced infectivity by 3.5 log10 TCID50/mL (99.97%) after 15 seconds exposure and eliminated detectable viral infectivity after 60 seconds;there was no effect on viral RNA detection by PCR. In vivo, culturable virus (VOC beta/B.1.351 variant) was obtained from 6 of 14 PCRconfirmed positive subjects;in these subjects, 5 minutes after the single PVP-I dose, the mean viral titre was reduced by 65% versus baseline and by 79% versus baseline at 60 minutes post-dose. 5 of the 6 subjects (83%), had reduction or cessation of viral shedding at 5 minutes in all 6 subjects, virus titers 60 minutes post-dose were below baseline value. 0.5% PVP-I treatment didn’t interfere with the laboratory diagnosis of COVID-19 via PCR-detection of viral RNA in humans. Conclusions: 0.5% PVP-I nasal spray is rapidly virucidal to SARS-CoV-2 in vitro using exposure times consistent with nasal residence;single in vivo nasal administration reduced infectious viral titers in COVID-19 subjects with culturable virus. A single application of 0.5% PVP-I nasal spray does not interfere with PCR-mediated laboratory diagnosis of COVID-19. We are undertaking a large double blinded randomized controlled trial to confirm if repeated application of 0.5% PVP-I nasal spray over a longer period could be useful in suppressing viral shedding and transmission risk in COVID-positive patients. © Australian Journal of Otolaryngology. All rights reserved.

Nurses Are More Exhausted Than Ever: What Should We Do About It? A review of the evidence leads to timely recommendations

For nurses, the challenges posed by demanding work environments and schedules often lead to fatigue, and this can be exacerbated during crises like the COVID-19 pandemic. In this article, the authors discuss causes and challenges of nurse fatigue and consider several evidence-based strategies and solutions for individual nurses and organizations. Barriers to implementation, including a negative workplace culture and inadequate staffing, are also described, and several resources are presented.

Anticipating revisions in the transportation services index

The Transportation Services Index (TSI) lags two months from its release date due to source data availability, and it is desirable to publish a preliminary TSI that is advanced two months ahead. We model and forecast TSI with a co-integrated Vector Autoregression, also considering two explanatory series that do not have publication delay. Thus we are able to produce forecasts and nowcasts of the index, and we demonstrate that – during normal economic conditions – out-of-sample performance is within the scope expected by the forecast confidence intervals. We also examine the performance of the models at the onset of the COVID-19 pandemic, and the large forecast errors at this regime change are beyond the bounds indicated by our model. The practical ramifications of this methodology is discussed. [ABSTRACT FROM AUTHOR] Copyright of Statistical Journal of the IAOS is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Restarting plastic surgery: Drawing on the experience of the initial COVID-19 pandemic to inform the safe resumption of services.

Coronavirus disease-2019 (COVID-19) has caused an unprecedented demand on healthcare resources globally. In the light of the arrival of a novel contagious and life-threatening virus, the NHS has responded by making difficult decisions to maintain care for patients and protect staff. The response has been frequently amended following updates in the UK Government policy as scientific understanding of the virus has improved. Our Plastic Surgery practice has adapted to mitigate risk to patients by reducing face-to-face contact, downgrading emergency procedures and deferring elective surgery where possible. This has inevitably resulted in a backlog in elective surgery and outpatient appointments. An assessment of the long-term health, social and economic impact of NHS wide service reconfiguration upon patient outcomes is yet to be seen. In this paper, we review the demonstrable early effects of service changes upon our unit and compare those to national and internationally published data. We also outline some of the considerations being made as we consider strategies to resume services in the light of the ongoing COVID-19 pandemic.

A plastic surgery service response to COVID-19 in one of the largest teaching hospitals in Europe.

COVID-19 is presenting a colossal challenge to frontline NHS staff. This paper highlights how plastic surgery teams can use their diverse skills and resources in times of crisis. Through effective strategy and leadership we present how we are adapting as a department to serve our plastic surgery patients, other hospital teams and the Trust.