A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study) (preprint)

Objectives: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. Methods: FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected for daily seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. Results: Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. Conclusion: Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses.

Studying how administration route and dose regulates antibody generation against LNPs for mRNA delivery with single-particle resolution.

Following the recent approval of both siRNA- and mRNA-based therapeutics, nucleic acid therapies are considered a game changer in medicine. Their envisioned widespread use for many therapeutic applications with an array of cellular target sites means that various administration routes will be employed. Concerns exist regarding adverse reactions against the lipid nanoparticles (LNPs) used for mRNA delivery, as PEG coatings on nanoparticles can induce severe antibody-mediated immune reactions, potentially being boosted by the inherently immunogenic nucleic acid cargo. While exhaustive information is available on how physicochemical features of nanoparticles affects immunogenicity, it remains unexplored how the fundamental choice of administration route regulates anti-particle immunity. Here, we directly compared antibody generation against PEGylated mRNA-carrying LNPs administered by the intravenous, intramuscular, or subcutaneous route, using a novel sophisticated assay capable of measuring antibody binding to authentic LNP surfaces with single-particle resolution. Intramuscular injections in mice were found to generate overall low and dose-independent levels of anti-LNP antibodies, while both intravenous and subcutaneous LNP injections generated substantial and highly dose-dependent levels. These findings demonstrate that before LNP-based mRNA medicines can be safely applied to new therapeutic applications, it will be crucial to carefully consider the choice of administration route.

Cystic Fibrosis Learning Network Learning Structure for Multicenter Spread of Co-Production and Timely Patient Registry Data Entry Practices

Background: The Cystic Fibrosis Learning Network (CFLN) is a group of 34 programs that work and learn together with shared measures and processes to improve patient outcomes. Interventions are organized into change packages (collected, actionable concepts to share tested, refined ideas across multiple care centers). Since 2016, these change packages have helped advance team level co-production and improve timely data entry (TDE) and quality and use of Cystic Fibrosis Foundation Patient Registry (CFFPR) data. In the context of the COVID-19 pandemic, in-person meetings were curtailed, and team membership changed often. New learning structures to promote peer-to-peer learning were needed to spread and sustain these interventions. The objective was to describe the shared multicenter learning method used to spread practices in two series: co-production (recruitment and onboarding of patient and family partners (PFPs)) and TDE entry into the CFFPR. Method(s): In the design phase of the learning structure, we developed objectives specific to each series. Community content experts refined the curriculum from the established change package concepts. Teams were recruited through an open invitation to all CFLN sites. and met virtually biweekly for 30-minute sessions for 10 to 12 weeks. CFLN content experts used the change packages to coach teams and share their experiences during learning structure huddles. These sessionswere followed by 2-week action periods to review and test change package ideas. Teams shared progress at each meeting in round-robin format. Progress toward smart aims, team experience, and participation were assessed using descriptive surveys before, during, at the end of the series, and 6 months after it closed. Result(s): In initial surveys, teams self-reported awide range of experiences with co-production and TDE into the CFFPR. Participating teamswere from pediatric and adult programs that varied in number of patients and geographic location. Four teams participated in the co-production series to recruit and onboard PFPs within 6 months of completion. In the 6-month follow-up survey, two of the four teams met their goal of recruiting and onboarding a new PFP. The remaining teams reported barriers related to institutional policies that limited training for volunteers. In the TDE series, five teams joined and aimed to improve TDE into the CFFPR within 8 months. All five teams are on target to meet this goal. For both series, action-period surveys revealed completion of tasks assigned (e.g., reviewof change package concepts, testing tools, process maps, barriers, facilitators). Feedback surveys collected during the final sessions of each series indicated that the learning structure helped teams meet expectations, learn something new, and increase confidence in the interventions. Conclusion(s): This learning structure for spreading standard interventions helped teams meet series' aims. The small-group structure allowed teams to learn and adapt coproduction and timely data change package ideas and sustain practices for at least 6 months. In future iterations, this learning structure could be used as a model to spread standard interventions to other programs in the CFLN and the larger care center network.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.

Bedside vs webside: Assessing patient-reported experiences for in-person and telemedicine-based perioperative evaluations.

BACKGROUND: Though telemedicine has been identified as safe and feasible, data on patient reported experiences (PREs) are lacking. We sought to compare PREs between in-person and telemedicine-based perioperative care. METHODS: Patients evaluated from August-November 2021 were prospectively surveyed to assess experiences and satisfaction with care rendered during in-person and telemedicine-based encounters. Patient and hernia characteristics, encounter related plans, and PREs were compared between in-person and telemedicine-based care. RESULTS: Of 109 respondents (86% response rate), 55% (n = 60) utilized telemedicine-based perioperative care. Indirect costs were lower for patients using telemedicine-based services, including work absence (3% vs. 33%, P < 0.001), lost wages (0% vs. 14%, P = 0.003), and requirements for hotel accommodations (0% vs. 12%, P = 0.007). PREs related to telemedicine-based care were non-inferior to in-person care across all measured domains (P > 0.4). CONCLUSIONS: Telemedicine-based care yields significant cost-savings over in-person care with similar patient satisfaction. These findings suggest that systems should focus on optimization of perioperative telemedicine services.

Dexamethasone for Inpatients With COVID-19 in a National Cohort.

Importance: Limited effective therapeutics are available to hospitalized patients with COVID-19. Clinical trials and observational studies have shown varying effects of systemic corticosteroids, including dexamethasone, in hospitalized patients with COVID-19, with limited descriptions of important patient subgroups. Objective: To examine the clinical use of dexamethasone for hospitalized patients with COVID-19 respiratory illness and to explore the heterogeneity of treatment outcomes across different subgroups. Design, Setting, and Participants: This is a retrospective, propensity score-weighted cohort study of adult patients hospitalized for at least 48 hours for COVID-19 respiratory illness between July 1, 2020, and October 31, 2021, at a large health care network of 156 hospitals across the US. Data analysis was performed from March 2022 to February 2023. Exposures: Systemic dexamethasone administered within 48 hours of either admission or escalation in oxygen support. Main Outcomes and Measures: All-cause in-hospital mortality or discharge to hospice. Results: A total of 80 699 patients who met the eligibility criteria were identified (median [IQR] age, 64 [52-76] years; 37 606 women [46.6%]); 13 230 patients (16.4%) identified as Black, 49 222 (60.9%) as White, 18 247 (22.6%) as other race, and 20 340 (25.2%) as Hispanic ethnicity. Of these patients, 13 040 (16.2%) did not require supplemental oxygen within 48 hours of admission, 56 368 (69.8%) required supplemental oxygen, 7618 (9.4%) required noninvasive positive pressure ventilation (NIPPV), and 3673 (4.6%) required mechanical ventilation (MV) and/or extracorporeal membrane oxygenation (ECMO). After adjustment by propensity score overlap weighting, early use of dexamethasone was associated with reduction in a composite outcome of in-hospital mortality or discharge to hospice for patients receiving supplemental oxygen (aOR, 0.92; 95% CI, 0.86-0.98) and MV and/or ECMO (aOR, 0.82; 95% CI, 0.68-0.99). In contrast, all-cause inpatient mortality or discharge to hospice was not lower for patients who received dexamethasone in the no supplemental oxygen group (aOR, 0.90; 95% CI, 0.78-1.03) and in the NIPPV group (aOR, 0.87; 95% CI, 0.73-1.04). Importantly, patients with more comorbidities had greater benefit from dexamethasone use. Conclusions and Relevance: In this national multicenter cohort study of inpatients with COVID-19, early administration of dexamethasone was associated with significantly reduced odds of mortality or discharge to hospice in those requiring supplemental oxygen or MV and/or ECMO but not in those requiring no supplemental oxygen or NIPPV. These results support the continued use of systemic dexamethasone in patients hospitalized with COVID-19.

Impact of the Early COVID-19 Pandemic on the Number of HIV Preexposure Prophylaxis Uses and the Proportion of Preexposure Prophylaxis Users Receiving Sexually Transmitted Infection Testing Services.

BACKGROUND: With the potential impact of the COVID-19 pandemic on HIV preexposure prophylaxis (PrEP) care management, we assessed the number of PrEP users and sexually transmitted infection (STI) testing-eligible PrEP users, STI testing rates, and prevalence between prepandemic (January 1, 2018-March 31, 2020) and early-pandemic (April 1, 2020-September 30, 2020) periods. METHODS: In this retrospective cohort study, a PrEP user for a given quarter is defined as either a previous PrEP user or a PrEP initiator who has at least 1-day coverage of tenofovir/emtricitabine in the given quarter. The STI testing-eligible PrEP users for a given quarter were defined as those persons whose runout date (previous dispense date + days of tenofovir/emtricitabine supply) was in the given quarter. RESULTS: The quarterly number of PrEP users increased from the first quarter of 2018 to the first quarter of 2020 and then decreased in the second and third quarter of 2020. Among STI testing-eligible PrEP users who had ≤14 days between runout and next refill date, gonorrhea and chlamydia screening testing rates were 95.1% for prepandemic and 93.4% for early pandemic ( P = 0.1011). Among all STI testing-eligible PrEP users who were tested for gonorrhea and chlamydia, gonorrhea prevalence was 6.7% for prepandemic and 5.7% for early pandemic ( P = 0.3096), and chlamydia prevalence was 7.0% for prepandemic and 5.8% for early pandemic ( P = 0.2158). CONCLUSIONS: Although the early COVID-19 pandemic resulted in lower numbers of PrEP users and PrEP initiators, individuals who remained continuous users of PrEP maintained extremely high rates of bacterial STI screening. With high STI prevalence among PrEP users, assessments of PrEP care management are continuously needed.

Evaluation of [18F]Favipiravir in Rodents and Nonhuman Primates (NHP) with Positron Emission Tomography.

The COVID-19 pandemic has posed a significant challenge to global public health. In response, the search for specific antiviral drugs that can effectively treat the disease caused by the SARS-CoV-2 virus has become a priority. While significant progress has been made in this regard, much work remains to address this ongoing crisis effectively. Favipiravir is an antiviral drug initially developed for the treatment of influenza and has received approval for emergency use for COVID-19 in many countries. A better understanding of the biodistribution and pharmacokinetics of Favipiravir in vivo would facilitate the development and translation of clinical antiviral drugs for COVID-19. Herein, we report the evaluation of [18F]Favipiravir in naive mice, transgenic mice models of Alzheimer's disease, and nonhuman primates (NHP) with positron emission tomography (PET). The [18F]Favipiravir was obtained in an overall decay-corrected radiochemical yield of 29% with a molar activity of 25 GBq/µmol at the end of synthesis (EOS). PET imaging in naive mice, transgenic mice models of Alzheimer's disease, and nonhuman primates revealed a low initial brain uptake, followed by a slow washout of [18F]Favipiravir in vivo. The [18F]Favipiravir was eliminated by a combination of hepatobiliary and urinary excretion. The low brain uptake was probably attributed to the low lipophilicity and low passive permeability of the drug. We hope this proof-of-concept study will provide a unique feature to study antiviral drugs using their corresponding isotopologues by PET.

Stress, intertemporal choice, and mitigation behavior during the COVID-19 pandemic.

Delayed gratification is an important focus of research, given its potential relationship to forms of behavior, such as savings, susceptibility to addiction, and pro-social behaviors. The COVID-19 pandemic may be one of the most consequential recent examples of this phenomenon, with people's willingness to delay gratification affecting their willingness to socially distance themselves. COVID-19 also provides a naturalistic context by which to evaluate the ecological validity of delayed gratification. This article outlines four large-scale online experiments (total N = 12, 906) where we ask participants to perform Money Earlier or Later (MEL) decisions (e.g., $5 today vs. $10 tomorrow) and to also report stress measures and pandemic mitigation behaviors. We found that stress increases impulsivity and that less stressed and more patient individuals socially distanced more throughout the pandemic. These results help resolve longstanding theoretical debates in the MEL literature as well as provide policymakers with scientific evidence that can help inform response strategies in the future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Preliminary Efficacy of a Theory-Informed Intervention to Increase COVID-19 Testing Uptake Among People Who Inject Drugs in San Diego County: Findings From a Pilot Randomized Controlled Trial.

BACKGROUND: People who inject drugs (PWID) have low rates of COVID-19 testing yet are vulnerable to severe disease. In partnership with a mobile syringe service program (SSP) in San Diego County, CA, we developed the evidence-, community-, and Social Cognitive Theory-informed "LinkUP" intervention (tailored education, motivational interviewing, problem-solving, and planning) to increase COVID-19 testing uptake among PWID. PURPOSE: To assess preliminary efficacy of LinkUP in increasing PWID COVID-19 testing in a pilot randomized controlled trial (RCT). METHODS: We referred participants (PWID, ≥18 years old, San Diego County residents who had not recently undergone voluntary COVID-19 testing) to mobile SSP sites that had been randomized (by week) to offer the active LinkUP intervention or didactic attention-control conditions delivered by trained peer counselors. Following either condition, counselors offered on-site rapid COVID-19 antigen testing. Analyses estimated preliminary intervention efficacy and explored potential moderation. RESULTS: Among 150 participants, median age was 40.5 years, 33.3% identified as Hispanic/Latinx, 64.7% were male, 73.3% were experiencing homelessness, and 44.7% had prior mandatory COVID-19 testing. The LinkUP intervention was significantly associated with higher COVID-19 testing uptake (p < .0001). Homelessness moderated intervention effects; LinkUP increased COVID-19 testing uptake more among participants experiencing homelessness (adjusted risk ratio [aRR]: 1.80; 95% CI: 1.56-2.09; p < .0001) than those not experiencing homelessness (aRR: 1.20; 95% CI: 1.01-1.43; p = .04). CONCLUSIONS: Findings from this pilot RCT support the preliminary efficacy of the "LinkUP" intervention to increase COVID-19 testing among PWID and underscore the importance of academic-community partnerships and prevention service delivery through SSPs and other community-based organizations serving vulnerable populations.

People who inject drugs (PWID) are vulnerable to severe COVID-19 disease yet have low rates of COVID-19 testing. We partnered with a syringe service program (SSP) in San Diego County, CA, to develop "LinkUP," an evidence- and community-informed intervention. Specifically, LinkUP used tailored education, motivational interviewing, and problem-solving and planning strategies to increase COVID-19 testing uptake among PWID. This study was a pilot randomized controlled trial (RCT) designed to assess the preliminary efficacy of LinkUP in increasing PWID COVID-19 testing. We referred participants (PWID, ≥18 years old, San Diego residents without recent voluntary COVID-19 testing) to mobile SSP sites that had been randomized (by week). Trained peer counselors then offered LinkUP or an educational control condition lasting the same length (~30 minutes). After either condition, counselors offered on-site rapid COVID-19 antigen testing. Among 150 participants, our analyses found that the LinkUP intervention was associated with higher COVID-19 testing uptake, especially for participants experiencing homelessness. In summary, our findings from this pilot RCT support the preliminary efficacy of the "LinkUP" intervention in increasing COVID-19 testing among PWID. This study also underscores the importance of academic-community partnerships and prevention service delivery through SSPs and other community-based organizations serving vulnerable populations.

Toward reciprocity in healing: Introduction to the special issue

The article presents an introduction to the special issue on reciprocity. The notion of reciprocity was the primary confluence theme. The word reciprocal comes from the Latin, reciprocus, meaning to move backward and forward. Reciprocity is easy enough to understand as a concept, but it is challenging to manifest. We are habitually human-focused, continuously concerned with ourselves, and too commonly unaware of ourselves as a profoundly impactful part of nature. As a consequence, we end up forgetting the other half of the equation, the back-and forth- ing required for all of us to be healthy. Confluence participants were encouraged to submit articles to this special issue of Ecopsychology, but the invitation for submissions went out more broadly to anyone inspired by the confluence themes. In the interval between the confluence and publication of this special issue, the world was turned upside down by the novel coronavirus. This pandemic and the isolation, reflection, and quarantines it has spawned made the fundamental human need to connect with the natural world even more self-evident, becoming the subject of numerous mainstream news stories and highlighting the value of Nature for human health. However, in the midst of widespread panic, it has created a context in which recognition of the healing value of nature was markedly one-sided, lacking in any impulse toward reciprocity. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

DREAMS After-School Programme for the Holistic Development of Children Amid Covid-19

After-school programmes (ASPs) help to facilitate students learning. DREAMS ASP facilitates schoolchildren with holistic development interventions at different locations. Due to the pandemic, DREAMS conducted their ASP in the online mode. The present study aims to narrate the case of ASP in the virtual mode and discuss participants experiences on holistic development at one of its locations. The study employed qualitative study designs. The sample of the study included participants from DREAMS ASP site at Kerala, India. The study interviewed four mentors, seven participants, and their parents to understand participants holistic development. However, the study excluded physical and spiritual aspects of holistic development. It found that the virtual DREAMS ASP was joyful, and there was a significant, positive change in all the selected dimensions of holistic development as reported by mentors, children, and parents. The study encourages future researchers to provide opportunities and frameworks to conduct more ASPs in India. © 2022 IGI Global. All rights reserved.

The moderating role of resilience in the relationship between experiences of COVID-19 response-related discrimination and disinformation among people who inject drugs

Background Due to the persistence of COVID-19, it remains important to measure and examine potential barriers to COVID-19 prevention and treatment to avert additional loss of life, particularly among stigmatized populations, such as people who inject drugs (PWID), who are at high risk for contracting and spreading SARS-CoV-2. We assessed the psychometrics of a novel COVID-19 response-related discrimination scale among PWID, and characterized associations between COVID-19 response-related discrimination, resilience to adversity, and endorsement of COVID-19 disinformation. Methods We assessed internal reliability, structural validity and construct validity of a 4-item COVID-19 response-related discrimination scale among PWID living in San Diego County, completing interviewer-administered surveys between October 2020 and September 2021. Using negative binomial regression, we assessed the relationship between COVID-19 response-related discrimination and disinformation and the potential moderating role of resilience. Results Of 381 PWID, mean age was 42.6 years and the majority were male (75.6%) and Hispanic (61.9%). The COVID-19 response-related discrimination scale had modest reliability (α=0.66, ω=0.66) as a single construct with acceptable construct validity (all p≤0.05). Among 216 PWID who completed supplemental surveys, a significant association between COVID-19 response-related discrimination and COVID-19 disinformation was observed, which was moderated by resilience (p=0.044). Specifically, among PWID with high levels of resilience, endorsement of COVID-19 disinformation significantly increased as exposure to COVID-19 response-related discrimination increased (p=0.011). Conclusions These findings suggest that intervening on COVID-19 response-related discrimination may offset the negative outcomes associated with COVID-19 disinformation.

Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Health workforce perceptions on telehealth augmentation opportunities.

BACKGROUND: The availability and use of telehealth to support health care access from a distance has expanded in response to the COVID-19 pandemic. Telehealth services have supported regional and remote health care access for many years and could be augmented to improve health care accessibility, acceptability and overall experiences for both consumers and clinicians. This study aimed to explore health workforce representatives' needs and expectations to move beyond existing telehealth models and plan for the future of virtual care. METHODS: To inform recommendations for augmentation, semi-structured focus group discussions were held (November-December 2021). Health workforce representatives with experience in health care delivery via telehealth across country Western Australia were approached and invited to join a discussion. RESULTS: Focus group participants included 53 health workforce representatives, with between two and eight participants per discussion. In total, 12 focus groups were conducted: seven were specific to regions, three with staff in centralised roles, and two with a mixture of participants from regional and central roles. Findings identified four key areas for telehealth augmentation: improvements required to existing service practice and processes; equity and access considerations; health workforce-focussed opportunities; and consumer-focussed opportunities. CONCLUSIONS: Following the onset of the COVID-19 pandemic and the rapid increase in health services delivered via telehealth modalities, it is timely to explore opportunities to augment pre-existing models of care. Workforce representatives consulted in this study suggested modifications to existing process and practice that would improve the current models of care, and recommendations on ways to improve clinician and consumer experiences with telehealth. Improving experiences with virtual delivery of health care is likely to support continued use and acceptance of this modality in health care delivery.

Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine.

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3-4 weeks after the first vaccination dose but before the second dose, and 2-6 months after the second (booster) dose. The blood plasma concentration of antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector antibodies.

Modeling COVID-19 disease processes by remote elicitation of causal Bayesian networks from medical experts.

BACKGROUND: COVID-19 is a new multi-organ disease causing considerable worldwide morbidity and mortality. While many recognized pathophysiological mechanisms are involved, their exact causal relationships remain opaque. Better understanding is needed for predicting their progression, targeting therapeutic approaches, and improving patient outcomes. While many mathematical causal models describe COVID-19 epidemiology, none have described its pathophysiology. METHODS: In early 2020, we began developing such causal models. The SARS-CoV-2 virus's rapid and extensive spread made this particularly difficult: no large patient datasets were publicly available; the medical literature was flooded with sometimes conflicting pre-review reports; and clinicians in many countries had little time for academic consultations. We used Bayesian network (BN) models, which provide powerful calculation tools and directed acyclic graphs (DAGs) as comprehensible causal maps. Hence, they can incorporate both expert opinion and numerical data, and produce explainable, updatable results. To obtain the DAGs, we used extensive expert elicitation (exploiting Australia's exceptionally low COVID-19 burden) in structured online sessions. Groups of clinical and other specialists were enlisted to filter, interpret and discuss the literature and develop a current consensus. We encouraged inclusion of theoretically salient latent (unobservable) variables, likely mechanisms by extrapolation from other diseases, and documented supporting literature while noting controversies. Our method was iterative and incremental: systematically refining and validating the group output using one-on-one follow-up meetings with original and new experts. 35 experts contributed 126 hours face-to-face, and could review our products. RESULTS: We present two key models, for the initial infection of the respiratory tract and the possible progression to complications, as causal DAGs and BNs with corresponding verbal descriptions, dictionaries and sources. These are the first published causal models of COVID-19 pathophysiology. CONCLUSIONS: Our method demonstrates an improved procedure for developing BNs via expert elicitation, which other teams can implement to model emergent complex phenomena. Our results have three anticipated applications: (i) freely disseminating updatable expert knowledge; (ii) guiding design and analysis of observational and clinical studies; (iii) developing and validating automated tools for causal reasoning and decision support. We are developing such tools for the initial diagnosis, resource management, and prognosis of COVID-19, parameterized using the ISARIC and LEOSS databases.

The Epidemiology and Costs of Disease Intervention Specialist Retention.

BACKGROUND: The COVID-19 pandemic changed the environment in which disease intervention specialists (DISs) operate, as their skills were in demand beyond sexually transmitted disease (STD) control programs. Workforce conditions generally have changed in the last 2 years, imposing additional challenges. Retaining STD DIS has become more difficult in the changed environment. MATERIALS AND METHODS: We conducted a landscape scan and obtained data from literature and personal observations to characterize current DIS workforce issues. We used published employment data to characterize current labor market conditions and described how cost-effectiveness analysis could be used to assess potential DIS retention interventions. An example illustrating cost-effectiveness concepts was developed. RESULTS: Many STD control programs faced difficulties in retaining STD DIS, because competing positions often could be done without field work. Economic and crime issues posed additional challenges. General workforce turnover has increased 33% since 2016. Turnover varies by age, sex, and education. Cost-effectiveness analysis can be used to assess DIS retention interventions, but data on costs and outcomes are needed on an ongoing basis. Changes in the workforce environment could impact both retention and the effectiveness of retention interventions. CONCLUSIONS: Workforce changes have impacted employee retention. Increased federal funding makes expansion of the DIS workforce possible, but the labor market environment will continue to pose challenges to recruitment and retention.

The moderating role of resilience in the relationship between experiences of COVID-19 response-related discrimination and disinformation among people who inject drugs.

BACKGROUND: Due to the persistence of COVID-19, it remains important to measure and examine potential barriers to COVID-19 prevention and treatment to avert additional loss of life, particularly among stigmatized populations, such as people who inject drugs (PWID), who are at high risk for contracting and spreading SARS-CoV-2. We assessed the psychometrics of a novel COVID-19 response-related discrimination scale among PWID, and characterized associations between COVID-19 response-related discrimination, resilience to adversity, and endorsement of COVID-19 disinformation. METHODS: We assessed internal reliability, structural validity and construct validity of a 4-item COVID-19 response-related discrimination scale among PWID living in San Diego County, completing interviewer-administered surveys between October 2020 and September 2021. Using negative binomial regression, we assessed the relationship between COVID-19 response-related discrimination and disinformation and the potential moderating role of resilience. RESULTS: Of 381 PWID, mean age was 42.6 years and the majority were male (75.6 %) and Hispanic (61.9 %). The COVID-19 response-related discrimination scale had modest reliability (α = 0.66, ω = 0.66) as a single construct with acceptable construct validity (all p ≤ 0.05). Among 216 PWID who completed supplemental surveys, a significant association between COVID-19 response-related discrimination and COVID-19 disinformation was observed, which was moderated by resilience (p = 0.044). Specifically, among PWID with high levels of resilience, endorsement of COVID-19 disinformation significantly increased as exposure to COVID-19 response-related discrimination increased (p = 0.011). CONCLUSIONS: These findings suggest that intervening on COVID-19 response-related discrimination may offset the negative outcomes associated with COVID-19 disinformation.