Evaluation of the readability, understandability, and actionability of COVID-19 public health messaging in Atlantic Canada

IntroductionEffective communication of COVID-19 information involves clear messaging to ensure that readers comprehend and can easily apply behavioral recommendations. This study evaluated the readability, understandability, and actionability of public health resources produced by the four provincial governments in Atlantic Canada (New Brunswick, Newfoundland and Labrador, Nova Scotia, and Prince Edward Island). MethodsA total of 400 web-based resources were extracted in June 2022 and evaluated using the Flesch-Kincaid Grade Level, CDC Clear Communication Index, and the Patient and Education Materials Assessment Tool. Descriptive statistics and a comparison of mean scores were conducted across provinces and type of resources (e.g., text, video). ResultsOverall, readability of resources across the region exceeded recommendations, requiring an average Grade 11 reading level. Videos and short form communication resources, including infographics, were the most understandable and actionable. Mean scores across provinces differed significantly on each tool;Newfoundland and Labrador produced materials that were most readable, understandable, and actionable, followed by New Brunswick. DiscussionRecommendations on improving clarity of COVID-19 resources are described. Careful consideration in the development of publicly available resources is necessary in supporting COVID-19 knowledge uptake, while reducing the prevalence of misinformation.

Acceptability of an mHealth App for Monitoring Perinatal and Postpartum Mental Health: Qualitative Study With Women and Providers.

BACKGROUND: Up to 15% of pregnant and postpartum women commonly experience undiagnosed and untreated mental health conditions, such as depression and anxiety, which may result in serious health complications. Mobile health (mHealth) apps related to mental health have been previously used for early diagnosis and intervention but not among pregnant and postpartum women. OBJECTIVE: This study aims to assess the acceptability of using mHealth to monitor and assess perinatal and postpartum depression and anxiety. METHODS: Focus group discussions with pregnant and postpartum women (n=20) and individual interviews with health care providers (n=8) were conducted to inform the acceptability of mHealth and determine its utility for assessing perinatal and postpartum mood symptoms. Participants were recruited via purposive sampling from obstetric clinics and the surrounding community. A semistructured interview guide was developed by an epidemiologist with qualitative research training in consultation with an obstetrician. The first author conducted all focus group discussions and provider interviews either in person or via Zoom (Zoom Video Communications, Inc) depending on the COVID-19 protocol that was in place during the study period. All interviews were audio recorded with consent; transcribed; and uploaded for coding to ATLAS.ti 8 (ATLAS.ti Scientific Software Development Gmb H), a qualitative data analysis and retrieval software. Data were analyzed using the deductive content analysis method using a set of a priori codes developed based on the interview guide. Methodological rigor and quality were ensured by adopting a systematic approach during the implementation, data collection, data analysis, and reporting of the data. RESULTS: Almost all women and providers had downloaded and used at least 1 health app. The respondents suggested offering short questions in layperson language that could be understood by women of all educational levels and offering no more than 2 to 3 assessments per day at preferred timings decided by the women themselves. They also suggested that the women themselves receive the alerts first, with other options being family members, spouses, or friends if the women themselves did not respond within 24 to 72 hours. Customization and snooze features were strongly endorsed by women and providers to improve acceptability and utility. Women mentioned competing demands on their time during the postpartum period, fatigue, privacy, and the security of mental health data as concerns. Health care professionals highlighted the long-term sustainability of app-based mood assessment and monitoring as an important challenge. CONCLUSIONS: The findings from this study show that mHealth would be acceptable to pregnant and postpartum women for monitoring mood symptoms. This could inform the development of clinically meaningful and inexpensive tools for facilitating the continuous monitoring of, the early diagnosis of, and an early intervention for mood disorders in this vulnerable population.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor-binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are unique in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

hACE2-Induced Allosteric Activation in SARS-CoV versus SARS-CoV-2 Spike Assemblies Revealed by Structural Dynamics.

SARS-CoV and SARS-CoV-2 cell entry begins when spike glycoprotein (S) docks with the human ACE2 (hACE2) receptor. While the two coronaviruses share a common receptor and architecture of S, they exhibit differences in interactions with hACE2 as well as differences in proteolytic processing of S that trigger the fusion machine. Understanding how those differences impact S activation is key to understand its function and viral pathogenesis. Here, we investigate hACE2-induced activation in SARS-CoV and SARS-CoV-2 S using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS revealed differences in dynamics in unbound S, including open/closed conformational switching and D614G-induced S stability. Upon hACE2 binding, notable differences in transduction of allosteric changes were observed extending from the receptor binding domain to regions proximal to proteolytic cleavage sites and the fusion peptide. Furthermore, we report that dimeric hACE2, the native oligomeric form of the receptor, does not lead to any more pronounced structural effect in S compared to saturated monomeric hACE2 binding. These experiments provide mechanistic insights into receptor-induced activation of Sarbecovirus spike proteins.

Web-based pediatric visual acuity testing at home

Introduction: Pediatric eye care access, particularly in rural areas, has been an ongoing concern. The COVID-19 pandemic has led to a growing appreciation and acceptance of a role for telemedicine in pediatric eye care. However, many at-home visual acuity (VA) charts and apps have poor test design or inaccurate optotype sizes, and may passively provide misinformation for clinical decision making.1-3 We evaluated the new M&S EyeSimplify At-Home Visual Acuity Tests, which include web-based versions of the ATS-HOTV and E-ETDRS tests commonly used in clinical trials. Method(s): Children with and without VA deficits were enrolled. In-office VA was tested with the M&S Smart System ATS-HOTV (ages 3-6;N = 34;68 eyes) or E-ETDRS (ages 7-12;N = 31;62 eyes) protocol. The child was registered on the EyeSimplify web-based portal and the parent was emailed a link to the at-home VA test. The portal notified us when at-home testing was completed and provided us on-line access to VA results. Equivalence of the two test settings was evaluated by mean difference and 95% limits of agreement (LOA) using Bland-Altmann analysis. Result(s): The mean difference between in-office and at-home was small for both ATS-HOTV (0.01 + 0.08 logMAR) and E-ETDRS 0.04 + 0.08 logMAR;95% LOA = -0.15 to 0.17 and -0.11 to 0.19, respectively, comparable to test-retest agreement in an office setting. Conclusion/Relevance: The M&S EyeSimplify At-Home Visual Acuity Tests provided VA equivalent to in-office testing. If the burden of travel is significant, at-home testing may provide the information needed to continue care via telemedicine consultation when it might otherwise be discontinued or delayed.Copyright © 2022

Exploring Stroke Survivor and Staff Perceptions of an Intensive Virtual Upper Limb Programme

Introduction: The Queen Square Upper Limb (QSUL) Programme is a clinical service offering high dosage and intense rehabilitation to individuals with upper limb impairment following neurological injury. In response to COVID-19 pandemic, the QSUL Programme was adapted to a predominantly virtual service. The virtual programme consists of 1:1 Physiotherapy, Occupational Therapy and Rehabilitation Assistant sessions, groups, and independent practice. Patients engaged in an average of 83 hours of rehabilitation over four weeks including two face-to-face appointments for assessment. Here, we explore the perspectives of stroke survivors, carers and staff involved in the virtual QSUL programme. Method(s): Descriptive qualitative design using a conventional thematic content approach to analyse the data. Stroke survivors and caregivers who participated in the virtual upper limb programme and staff involved in service delivery were purposively sampled. Six focus groups were conducted with semi-structured interviews: four with stroke survivors (n=16) and carers(n=2) and two with staff (n=12). Result(s): Themes from stroke survivors and carers include (i) intensity and structured nature of the programme, (ii) value of goal directed and meaningful rehabilitation, (iii) camaraderie and shared experience gained from group interactions, (iv) importance of knowledgeable and empowering staff who could effectively deliver virtual therapy and (v) virtual rehabilitation was a 'good compromise' for face-to-face therapy. Conclusion(s): Stroke survivors and carers found the virtual upper limb programme to be intensive, individualised, and motivational. All groups identified positive and negative factors to virtual rehabilitation. Ongoing thematic analysis continues for staff focus groups.

A Prospective Study of Patient-Reported Quality of Life Outcomes in Standard and Expanded Endoscopic Endonasal Skull Base Surgery at a Tertiary Center

Introduction: Transient alterations in patient's quality of life (QOL) following endoscopic endonasal approach skull base surgery (EEA) are inevitable despite substantial progress in techniques and equipment over the last two decades. We have prospectively evaluated patient-reported QOL at our institution using multiple metrics, to better understand the sensitivity of such testing and evaluate for risk factors for worsened quality of life after EEA. Method(s): Prospective, review-board-approved, single-institution cohort study of patients undergoing EEA surgery between 2019 and 2022 (enrollment was paused March to September 2020 due to COVID-19 research restrictions). Patient-reported global PROMIS-29 and sinonasal-specific ASK-Nasal 12 metrics were obtained prior to and at routine intervals after EEA. Result(s): We enrolled 90 patients with baseline and follow-up data available. Average age was 50 years and there was a 58:32 female:male predominance. Most procedures involved at least transsellar (N = 73) surgery, although numerous expanded anatomic compartments (total N = 61) were also accessed. Pituitary adenoma was the most common pathology treated, although a wide range of others were represented. PROMIS-29 evaluation of global QOL demonstrated an expected worsening in symptoms within physical function (+2.9), social interaction (+1.1), and pain (+0.4) metrics at 2-weeks postoperatively compared with baseline;averages in these domains returned to baseline or were improved by 6 months. Anxiety and depression symptom domains were immediately improved as early as 2-weeks after surgery (-1.2 and -0.8, respectively), remaining improved compared with baseline 6 months after surgery. Sinonasal-specific QOL demonstrated expected worsening at 2 weeks postoperative (average sum ASK-Nasal 12 score 21, versus 9.7 baseline, p < 0.05) but returned to baseline at 6 months (average 9.2, p = NS). Subgroup analysis revealed that patients with functional pituitary adenoma (FPA) reported worse baseline global QOL in every PROMIS-29 domain, but similar baseline sinonasal-specific QOL, when compared with the entire cohort. FPA patients reported more absolute improvement in every domain of PROMIS-29 global QOL than did the cohort average at 6 months post-surgery (average change across all PROMIS-29 symptom domains at 6 months -1.96 for FPA, versus -1.2 for all patients, p < 0.05). Discussion(s): We prospectively assessed patient-reported global and sinonasal-specific QOL after EEA at a tertiary center using modern techniques. The PROMIS-29 global QOL metric has not been previously utilized in this patient group;expected postoperative alterations in physical and social function and pain were found and these resolved within six months of surgery. Patient symptoms in Anxiety and Depression QOL domains immediately improved at two weeks postoperatively despite objectively worse reported sinonasal QOL in the same time interval;this implies patients are strongly relieved to have completed surgery even if still suffering sinonasal QOL alterations in the early perioperative period. Patients with functional pituitary tumors have, not surprisingly, worse baseline global QOL than do average EEA patients;nevertheless, functional tumor patients also show more absolute improvement in QOL after surgery. (Figure Presented).

Hand care: it's time to take the gloves off

The increased incidence of hand dermatitis (HD) is well documented in healthcare professionals (HCPs) (Flyvholm MA, Bach B, Rose M, Jepsen KF. Self-reported hand eczema in a hospital population. Contact Dermatitis 2007;57: 110-15). It is reported that HD accounts for 95% of all occupational dermatitis (Bains SN, Nash P, Fonacier L. Irritant contact dermatitis. Clinic Rev Allergy Immunol 2019;56: 99-109). We sought to better understand the prevalence of HD in HCPs in a large teaching hospital, identify any associated risk factors and assess their knowledge of hand care. Additionally, we aimed to assess the availability of ward facilities and posters for hand hygiene and hand care. The survey was conducted between November 2015 and January 2016. A review of ward facilities and posters for hand care and hand hygiene was conducted in October 2020. A total of 820 HCPs responded to the survey. Altogether, 444 respondents (54 1%) reported a previous history of HD and 226 (27 6%) reported active dermatitis. These included 153 (18 6%) doctors/ dentists, 76 (9 3%) allied health professionals (AHPs), 46 (5 6%) nurses/midwives, 27 (3 3%) administrative staff, 16 (1 9%) other, five (0 6%) technicians and 108 (13 2%) medical/ dental/nursing/midwifery/AHP students. Only 10 (1 2%) took time off work owing to their HD, with five (0 6%) requiring > 5 days off work, but 67 (8 2%) wished they had taken time off work. In total, 416 (50 7%) respondents washed their hands > 20 times daily and 229 (27 9%) used disinfectants > 20 times per day. Those with a prior history of atopic dermatitis (AD) were at higher risk of developing HD [relative risk (RR) 1 69, 95% confidence interval (CI) 1 52-1 89;P < 0 001], and within 6 months of starting their job/placement (RR 1 82, 95% CI 1 3-2 5;P < 0 002). Only 107 (13 0%) respondents were able to identify all 11 correct statements regarding hand care. Two hundred and twenty (49 5%) of the 444 HCPs with a history of HD never received hand care advice when they started their current role. The 24 adult wards surveyed had a total of 162 general-use sinks, all with hand soap and disinfectant, and 154 hand hygiene posters. In contrast, only 22 sinks had emollients available. No posters were seen regarding hand care and skin health. This survey highlights the high prevalence of HD among HCPs, especially those with AD, but many are still not aware of good hand care measures. Additionally, our survey reflects the need for early education and equal facilities for hand care and hand hygiene, as both are important when delivering good clinical care, to protect patients and staff, especially in the midst of the COVID-19 pandemic.

Piloting an online telecoaching community-based exercise intervention with adults living with HIV: protocol for a mixed-methods implementation science study.

INTRODUCTION: Our aim is to evaluate the implementation of an online telecoaching community-based exercise (CBE) intervention with the goal of reducing disability and enhancing physical activity and health among adults living with HIV. METHODS AND ANALYSIS: We will conduct a prospective longitudinal mixed-methods two-phased intervention study to pilot the implementation of an online CBE intervention with ~30 adults (≥18 years) living with HIV who consider themselves safe to participate in exercise. In the intervention phase (0-6 months), participants will take part in an online CBE intervention involving thrice weekly exercise (aerobic, resistance, balance and flexibility), with supervised biweekly personal training sessions with a fitness instructor, YMCA membership providing access to online exercise classes, wireless physical activity monitor to track physical activity and monthly online educational sessions on topics related to HIV, physical activity and health. In the follow-up phase (6-12 months), participants will be encouraged to continue independent exercise thrice weekly. Quantitative assessment: Bimonthly, we will assess cardiopulmonary fitness, strength, weight, body composition and flexibility, followed by administering self-reported questionnaires to assess disability, contextual factor outcomes (mastery, engagement in care, stigma, social support), implementation factors (cost, feasibility, technology), health status and self-reported physical activity. We will conduct a segmented regression analyses to describe the change in level and trend between the intervention and follow-up phases. Qualitative assessment: We will conduct online interviews with a subsample of ~10 participants and 5 CBE stakeholders at baseline (month 0), postintervention (month 6) and end of follow-up (month 12) to explore experiences, impact and implementation factors for online CBE. Interviews will be audiorecorded and analysed using content analytical techniques. ETHICS AND DISSEMINATION: Protocol approved by the University of Toronto Research Ethics Board (Protocol # 40410). Knowledge translation will occur in the form of presentations and publications in open-access peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05006391.

Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study.

INTRODUCTION: Our aim was to describe episodic nature of disability among adults living with Long COVID. METHODS: We conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We recruited participants via collaborator community organisations in Canada, Ireland, UK and USA.We recruited adults who self-identified as living with Long COVID with diversity in age, gender, race/ethnicity, sexual orientation and duration since initial COVID infection between December 2021 and May 2022. We used a semistructured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis. RESULTS: Among the 40 participants, the median age was 39 years (IQR: 32-49); majority were women (63%), white (73%), heterosexual (75%) and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterised by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with 'ups and downs', 'flare-ups' and 'peaks' followed by 'crashes', 'troughs' and 'valleys', likened to a 'yo-yo', 'rolling hills' and 'rollercoaster ride' with 'relapsing/remitting', 'waxing/waning', 'fluctuations' in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterised as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health. CONCLUSION: Among this sample of adults living with Long COVID, experiences of disability were described as episodic, characterised by fluctuating health challenges, which may be unpredictable in nature. Results can help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.

An App-Based Ecological Momentary Assessment of Undergraduate Mental Health During the COVID-19 pandemic in Canada (Smart Healthy Campus Version 2.0): Longitudinal Study (preprint)

This paper presents results from the Smart Healthy Campus 2.0 study/smartphone app, developed and used to collect mental health-related lifestyle data from 86 Canadian undergraduates January - August 2021. This was a longitudinal repeat measures study conducted over 40 weeks. A 9-item mental health questionnaire was accessible once daily in the app. Two variants of this mental health questionnaire existed; the first was a weekly variant, available each Monday or until a participant responded during the week. The second was a daily variant available after the weekly variant. Mixed models were fit for responses to the two variants and 12 phone digital measures (e.g. GPS, step counts). A second round of models was fit based on backward elimination to determine associations between the 12 digital measures and the variants. 6518 digital measure samples and 1722 questionnaire responses were collected. The daily questionnaire had positive associations with floors walked, installed apps, and campus proximity, while having negative associations with uptime, and daily calendar events. Daily depression had a positive association with uptime. Daily resilience appeared to have a slight positive association with campus proximity. The weekly questionnaire variant had positive associations with device idling and installed apps, and negative associations with floors walked, calendar events, and campus proximity. Physical activity, weekly, had a negative association with uptime, and a positive association with calendar events and device idling. SHC 2.0, via phone digital measures, identified indicators of lifestyle that appeared to be associated with measures of mental health in undergraduates during COVID-19.

Cytoplasmic Tail Truncation Stabilizes S1-S2 Association and Enhances S Protein Incorporation into SARS-CoV-2 Pseudovirions.

Truncations of the cytoplasmic tail (CT) of entry proteins of enveloped viruses dramatically increase the infectivity of pseudoviruses (PVs) bearing these proteins. Several mechanisms have been proposed to explain this enhanced entry, including an increase in cell surface expression. However, alternative explanations have also been forwarded, and the underlying mechanisms for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein remain undetermined. Here, we show that the partial or complete deletion of the CT (residues 19 to 35) does not modify SARS-CoV-2 S protein expression on the cell surface when the S2 subunit is measured, whereas it is significantly increased when the S1 subunit is measured. We also show that the higher level of S1 in these CT-truncated S proteins reflects the decreased dissociation of the S1 subunit from the S2 subunit. In addition, we demonstrate that CT truncation further promotes S protein incorporation into PV particles, as indicated by biochemical analyses and cryo-electron microscopy. Thus, our data show that two distinct mechanisms contribute to the markedly increased infectivity of PVs carrying CT-truncated SARS-CoV-2 S proteins and help clarify the interpretation of the results of studies employing such PVs. IMPORTANCE Various forms of PVs have been used as tools to evaluate vaccine efficacy and study virus entry steps. When PV infectivity is inherently low, such as that of SARS-CoV-2, a CT-truncated version of the viral entry glycoprotein is widely used to enhance PV infectivity, but the mechanism underlying this enhanced PV infectivity has been unclear. Here, our study identified two mechanisms by which the CT truncation of the SARS-CoV-2 S protein dramatically increases PV infectivity: a reduction of S1 shedding and an increase in S protein incorporation into PV particles. An understanding of these mechanisms can clarify the mechanistic bases for the differences observed among various assays employing such PVs.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection (preprint)

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs, including recently circulating BA.4/BA.5, in both pseudovirus-based and live virus assays, and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

Identification and characterization of alternative sites and molecular probes for SARS-CoV-2 target proteins.

Three protein targets from SARS-CoV-2, the viral pathogen that causes COVID-19, are studied: the main protease, the 2'-O-RNA methyltransferase, and the nucleocapsid (N) protein. For the main protease, the nucleophilicity of the catalytic cysteine C145 is enabled by coupling to three histidine residues, H163 and H164 and catalytic dyad partner H41. These electrostatic couplings enable significant population of the deprotonated state of C145. For the RNA methyltransferase, the catalytic lysine K6968 that serves as a Brønsted base has significant population of its deprotonated state via strong coupling with K6844 and Y6845. For the main protease, Partial Order Optimum Likelihood (POOL) predicts two clusters of biochemically active residues; one includes the catalytic H41 and C145 and neighboring residues. The other surrounds a second pocket adjacent to the catalytic site and includes S1 residues F140, L141, H163, E166, and H172 and also S2 residue D187. This secondary recognition site could serve as an alternative target for the design of molecular probes. From in silico screening of library compounds, ligands with predicted affinity for the secondary site are reported. For the NSP16-NSP10 complex that comprises the RNA methyltransferase, three different sites are predicted. One is the catalytic core at the conserved K-D-K-E motif that includes catalytic residues D6928, K6968, and E7001 plus K6844. The second site surrounds the catalytic core and consists of Y6845, C6849, I6866, H6867, F6868, V6894, D6895, D6897, I6926, S6927, Y6930, and K6935. The third is located at the heterodimer interface. Ligands predicted to have high affinity for the first or second sites are reported. Three sites are also predicted for the nucleocapsid protein. This work uncovers key interactions that contribute to the function of the three viral proteins and also suggests alternative sites for ligand design.

Using Qualitative Systematic Review to Develop Practice Recommendations for Engaging Children and Adolescents with Cancer Less Than 18 Years in Their Treatment Decision Making

Background and Aims: Children and adolescents < 18 years (C&A) report varying treatment decision-making (TDM) preferences and experiences that might be distinct from what has been reported by their parents and clinicians. Identifying these distinctions will provide insight into care practices to meet child and adolescent's communication needs. Method(s): Using Joanna Briggs Institute meta-aggregation methods, we conducted a qualitative systematic review of the literature to describe child and adolescent (C&A) self-reported preferences for being involved in making their cancer treatment decisions (CTD). Parent or clinician responses were purposefully excluded from this review. PubMed, PsychINFO, CINAHL and SCOPUS database searches were completed in November 2019 and updated March 2022. Covidence screening software identified 46 studies (n=461 C&A across 15 countries) for synthesis and meta-aggregation (PROSPERO ID: CRD42021219107). We used Atlas.ti qualitative analysis software to extract and code C&A self-reported study findings. Result(s): Children and adolescents' self-reported experiences yielded nuanced TDM preferences. Decision types ranged from daily care decisions (e.g. pill vs. liquid medication) to disease-directed decisions (e.g. clinical trial) across the illness continuum. Many C&A did not perceive that there was a treatment choice to make other than following doctors' recommendations. Most C&A reported preferences for trusted adults (parents/clinicians) to make decisions;however, some youth also reported preferences to make their CTD. Younger children focused on daily care decisions related to their treatment, not CTDs. The youngest ages (<5 years) identified that complying with daily care is a decision. Children and adolescents also articulated their rationale for choices made. Conclusion(s): Our meta-aggregation provides a world wide description of child and adolescent cancer treatment decision-making. We also identified different contexts throughout the illness continuum that influence communication and decision-making at various stages of development. Synthesized findings from child and adolescent voices will identify evidence-based practice recommendations with a focus on meeting child and adolescent communication needs.

Comparing Aerosol Generation in Human and Animal Tissues During Common Otolaryngology Procedures

Introduction: The SARS-CoV-2 pandemic has highlighted the need to understand the risk of infection that aerosolized particles pose to surgeons and clinical staff during otolaryngology procedures. The objective of our study is to determine whether hamster and human tissues generate similar amounts of aerosolized particles using common otolaryngology surgical techniques to establish the translational value of modeling aerosol generation in human tissue with animal models. Method(s): Drilling, electrocautery, and coblation were performed on human and hamster tissues. Particle size and concentration were measured during the surgical procedures using a scanning mobility particle sizer and an aerosol particle sizer (SMPS-APS) and GRIMM aerosol particle spectrometer. Result(s): SMPS-APS and GRIMM measurements detected at least 2-fold increases in aerosol concentrations compared with baseline during all procedures. Procedures performed on human and hamster tissues produced similar trends and order of magnitude of aerosol concentrations. Generally, hamster tissues produced higher aerosol concentrations compared with human tissues, and some of these differences were statistically significant. Mean particles sizes for all procedures were small (<200 nm), although statistically significant differences in particle size were identified between human and hamster tissues during coblation and drilling (P=.001 and P<.001, respectively). Conclusion(s): Aerosol-generating procedures performed on human and hamster tissue produce similar trends in aerosol particle concentrations and sizes, although we observed some differences between the two tissue types. Further studies should be performed to understand the clinical significance of these differences.

Uncertainty, scarcity and transparency: Public health ethics and risk communication in a pandemic.

Communicating public health guidance is key to mitigating risk during disasters and outbreaks, and ethical guidance on communication emphasizes being fully transparent. Yet, communication during the pandemic has sometimes been fraught, due in part to practical and conceptual challenges around being transparent. A particular challenge has arisen when there was both evolving scientific knowledge on COVID-19 and reticence to acknowledge that resource scarcity concerns were influencing public health recommendations. This essay uses the example of communicating public health guidance on masking in the United States to illustrate ethical challenges of developing and conveying public health guidance under twin conditions of uncertainty and resource scarcity. Such situations require balancing two key principles in public health ethics: the precautionary principle and harm reduction. Transparency remains a bedrock value to guide risk communication, but optimizing transparency requires consideration of additional ethical values in developing and implementing risk communication strategies.