Changing Vaccine Assessment Criteria and Focus Towards Prevention Strategies

Objectives: To understand changes to granting access to novel vaccines by NITAG and payers and how prevention has become a focus in many markets Methods: Secondary research by studying various NITAG documents and published articles followed by primary research with experts in EU4 and UK Results: For NITAG recommendations, disease burden, vaccine efficacy, vaccine safety, followed by Epidemiology and mathematical modelling are conducted by most Western countries. Published studies on efficacy, effectiveness and reactogenicity are considered as key reference. UK specifically takes into account health economic modelling outputs. Recommendations in other markets are also considered in making local decisions. For vaccine funding payers consider the efficacy, durability and dosing regimen as key drivers, followed by aspects of strain coverage, formulation and storage. Platform were not considered by payers, while physicians considered it to be very important. For cost containment reasons, many NITAGs issue a recommendation for a narrow patient population Payers in all markets indicated that there is focus or prioritization of prevention strategies from ongoing COVID-19 pandemic and are likely to remain. UK for instance has increased its prevention budgets;however, this does not mean there is higher willingness to pay. In Germany there is no ring-fenced prevention specific budget. Conclusion(s): Severity of the disease is an important criterion in assessing the burden, an influential factor in vaccine decision making. In all countries in focus, Payers anticipate that the evaluation of new vaccines launched post-COVID-19 to be faster. Structural changes in Italy (restructure of AIFA and new NITAG) and UK (new public health agency), add to uncertainties on timelines. The length of the evaluation process will depends mainly on pre-work done with availability of local data on burden, epidemiology, and cost-effectiveness modelling.Copyright © 2023

Trends of Autologous Free-Flap Breast Reconstruction and Safety during the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Autologous free-flap breast reconstruction (ABR) is a valuable surgical option for patients following mastectomy. The coronavirus disease 2019 (COVID-19) pandemic has led to a myriad of factors that have affected access to care, hospital logistics, and postoperative outcomes. This study aims to identify differences in patient selection, hospital course and severity, and postoperative outcomes for patients who underwent ABR during and prior to the COVID-19 pandemic. METHODS: Patients undergoing ABR from the American College of Surgeons National Surgical Quality Improvement Program 2019 to 2020 database were analyzed to compare sociodemographics, hospital course, and outcomes over the first postoperative month. Multivariable logistic regression was used to identify factors predictive of complications based on the operative year. RESULTS: In total, 3,770 breast free flaps were stratified into two groups based on the timing of reconstruction (prepandemic and pandemic groups). Patients with a diagnosis of disseminated cancer were significantly less likely to undergo ABR during the COVID-19 pandemic. On univariate analysis, there were no significant differences in postoperative complications between the two groups. When controlling for potentially confounding sociodemographic and clinical risk factors, the COVID-19 group was significantly more likely to undergo reoperation compared with the prepandemic group (p < 0.05). CONCLUSION: When comparing outcomes for patients who underwent ABR prior to and during the COVID-19 pandemic, we found a significant increase in the odds of reoperation for those who had ABR during the pandemic. Debridement procedures and exploration for postoperative hemorrhage, thrombosis, or infection increased in the prepandemic group compared to the COVID-19 group. Notably, operative times decreased.

Extrafollicular IgD-CD27-CXCR5-CD11c- DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)-CD27-CXCR5-CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

Knowledge, attitudes, and behaviors with mask use and vaccines for COVID-19 prevention at 13 colleges and universities, April 2021.

Objectives: To understand college and university student knowledge, attitudes, and behaviors (KAB) regarding COVID-19 prevention strategies. Methods: Thirteen colleges and universities volunteered to conduct an anonymous electronic survey in April 2021 to assess students' KAB about mask use and vaccination to prevent COVID-19. Results: Three-quarters of students indicated they "Always" wore a mask correctly when in public indoor places. Of those not yet vaccinated, 55% expressed concern about unknown side effects. Over half of students were unsure or believe they do not need to continue wearing masks after vaccination and older students more likely to be vaccinated. There was a significant inverse correlation between intention of getting vaccinated and intention to attend a large indoor party without a mask. Conclusions: Colleges and universities are important to community efforts to slow the COVID-19 pandemic. The KAB findings can inform approaches to increase overall mask use and vaccination uptake among young students.

The impact of living through COVID-19 pandemic on mental health, food insecurity, loneliness and health behaviours in people with obesity.

OBJECTIVE: To examine the continued impact of the COVID-19 pandemic on the mental health of people living with obesity, and associations with food insecurity, loneliness, and health-related behaviours. METHODS: The study recruited 1187 UK adults living with obesity who completed an online survey, that examined mental health, and associations with food insecurity, loneliness, and health-related behaviours from July 2020 (end of the first UK lockdown) to the point they completed the survey in 2021. Regression analyses were used to examine relationships between outcome variables and demographic factors, and hierarchical linear regression models were used to assess levels of loneliness, depression, and wellbeing. RESULTS: Participants reported worse loneliness, depression, wellbeing, and food insecurity compared to pre-COVID. However, participants reported attempting to lose weight, healthier food shopping, diet, and increased physical activity. Quality and quantity of sleep deteriorated compared to prior to COVID-19. CONCLUSIONS: Adult living with obesity in the UK report a continued negative impact of the COVID-19 pandemic upon their mental health together with increased loneliness and food insecurity. However, our findings suggest that UK adults living with obesity have increased their engagement in positive health behaviours and were attempting to lose weight. This article is protected by copyright. All rights reserved.

N-of-1 trials versus usual care in children with hypertension: a pilot randomized clinical trial.

BACKGROUND: Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care. METHODS: A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10-22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary outcome was the proportion of patients with ambulatory BP control at 6 months in a Bayesian analysis. RESULTS: Among 49 participants (23 randomized to n-of-1 trials and 26 to usual care), mean age was 15.6 years. Using skeptical priors, we found a 69% probability that n-of-1 trials increased BP control at 6 months (Bayesian odds ratio (OR) 1.24 (95% credible interval (CrI) 0.51, 2.97), and 74% probability using neutral informed priors (OR 1.45 (95% CrI 0.48, 4.53). Systolic BP was reduced in both groups, with a 93% probability of greater reduction in the n-of-1 trial group (mean difference between groups = -3.6 mmHg (95%CrI -8.3, 1.28). There was no significant difference in side effect experience or caregiver satisfaction. CONCLUSIONS: Among hypertensive adolescents and young adults, n-of-1 trials with ambulatory BP monitoring likely increased the probability of BP control. A large trial is needed to assess their use in clinical practice.

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.

BACKGROUND: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. METHODS: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. FINDINGS: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The 'beta variant' RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. INTERPRETATION: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. FUNDING: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Climate disasters, altered migration and pandemic shocks: (im)mobilities and interrelated struggles in a border region

Shocks linked to climate disasters are increasingly understood as intertwined with inequities, devastating livelihoods, exacerbating food insecurities and impacting migration economies. Yet there is often a lack of sustained and situated attention to how these – and diverse secondary and tertiary shocks – are experienced in relation to gender and class inequalities, other social differences and underlying forces shaping differentiated mobility-related challenges over time. Divergent experiences and histories of shocks are often simplified, with (im)mobility-related struggles misunderstood or only ly represented. Amid these concerns, this article explores the 'mobilities turn' in climate disaster research, focusing on experiences articulated by people along the Zimbabwe-Mozambique border, examining multiple impacts of climate disasters and changing dynamics of (im)mobility converging with pandemic shocks and interrelated political and socio-economic struggles. In this region, impacted by one of the world's most severe tropical cyclones in recent memory, we explore the embeddedness of shocks in dynamic political-economic landscapes and life trajectories. Part of a multi-method 5-year project, we focus on stories where articulations around mobilities, translocal connections and mobility disruptions, including from COVID-19, call for carefully understanding socio-economic ties and histories, land alienation and access inequities, mutating meanings of borders, and factors intensifying economic insecurities amid increasingly severe and frequent climate shocks. [ FROM AUTHOR] Copyright of Mobilities is the property of Routledge 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 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 . (Copyright applies to all s.)

Psychological and developmental concerns in child and adolescent athletes

The worldwide appeal of sports-whether soccer, the NFL, tennis, street basketball, skiing, pickup stickball, curling, etc.-has never been clearer since the interruption of sports during the COVID-19 pandemic. People were willing to make tremendous accommodations and endure heightened risk to play or watch sports. Across local communities, parents encourage their children to get involved in organized sports, and coaches see sports as a great vehicle for youth development or, at times, furthering their own prominence. For a variety of reasons, youth sport has become an arena for pressured performance, leading to or exacerbating mental health problems in child and adolescent "athletes." In this chapter, with coaches as our particular audience because of their critical role, we focus primarily on sport-related anxiety, depression, disordered eating, and substance misuse. We review the range of symptoms and experiences that fall under each of these categories and consider how they present in childhood and adolescence. We want coaches (and other caregivers) to confidently identify early signs of dysfunction, sensitively and competently broach the subject with all involved, and refer youth athletes to appropriate mental health services as needed, thereby serving as catalysts for mental health. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Pandemic restrictions in 2020 highlight the significance of non-road NOx sources in central London

Fluxes of nitrogen oxides (NOx=NO+NO2) and carbon dioxide (CO2) were measured using eddy covariance at the British Telecommunications (BT) Tower in central London during the coronavirus pandemic. Comparing fluxes to those measured in 2017 prior to the pandemic restrictions and the introduction of the Ultra-Low Emissions Zone (ULEZ) highlighted a 73 % reduction in NOx emissions between the two periods but only a 20 % reduction in CO2 emissions and a 32 % reduction in traffic load. Use of a footprint model and the London Atmospheric Emissions Inventory (LAEI) identified transport and heat and power generation to be the two dominant sources of NOx and CO2 but with significantly different relative contributions for each species. Application of external constraints on NOx and CO2 emissions allowed the reductions in the different sources to be untangled, identifying that transport NOx emissions had reduced by >73 % since 2017. This was attributed in part to the success of air quality policy in central London but crucially due to the substantial reduction in congestion that resulted from pandemic-reduced mobility. Spatial mapping of the fluxes suggests that central London was dominated by point source heat and power generation emissions during the period of reduced mobility. This will have important implications on future air quality policy for NO2 which, until now, has been primarily focused on the emissions from diesel exhausts.

Antibody dependent disease enhancement (ADE) after COVID-19 vaccination and beta glucans as a safer strategy in management.

A potential risk associated with vaccines for COVID-19 is antibody-dependent disease enhancement (ADE) in which vaccine induced antibody mediated immune responses may lead to enhanced SARS CoV- 2 acquisition or increased disease severity. Though ADE has not been clinically demonstrated with any of the COVID-19 vaccines so far, when neutralizing antibodies are suboptimal, the severity of COVID-19 has been reported to be greater. ADE is presumed to occur via abnormal macrophages induced by the vaccine based immune response by antibody-mediated virus uptake into Fc gamma receptor IIa (FcγRIIa) or by the formation of Fc-mediated excessive antibody effector functions. Beta-glucans which are naturally occurring polysaccharides known for unique immunomodulation by capability to interact with macrophages, eliciting a specific beneficial immune-response and enhancing all arms of the immune system, importantly without over-activation are suggested as safer nutritional supplement-based vaccine adjuvants for COVID-19.

COVID-19-Related Medical Vulnerability and Mental Health Outcomes Among US First Responders.

OBJECTIVE: The present investigation examined the main and interactive effects of coronavirus disease 2019 (COVID-19)-related medical vulnerability (CMV; the number of medical conditions with potential to elevate COVID-19 risk) and first responder status (emergency medical services roles vs non-emergency medical services roles) on mental health symptoms. METHODS: A national sample of 189 first responders completed an online survey between June and August 2020. Hierarchal linear regression analyses were conducted and included the following covariates: years served as a first responder, COVID-19 exposure, and trauma load. RESULTS: Unique main and interactive effects emerged for both CMV and first responder status. COVID-19-related medical vulnerability was uniquely associated with anxiety and depression, but not alcohol use. Simple slope analyses revealed divergent results. CONCLUSIONS: Findings suggest that first responders with CMV are more likely to experience anxiety and depressive symptoms and that these associations may vary by first responder role.

Cochlear Implantation in Adults With Single-Sided Deafness: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the clinical outcomes of adult patients with single-sided deafness (SSD) undergoing ipsilateral cochlear implantation. DATA SOURCE: An electronic search of Medline and Embase articles. REVIEW METHODS: A systematic review was performed with a search strategy developed by a licensed librarian to identify studies of adult patients with SSD who underwent ipsilateral cochlear implantation. Articles were managed in Covidence and evaluated by 2 independent reviewers. Risk of bias was assessed and data were extracted, including patient demographics, etiology of deafness, duration of deafness, and postoperative change in speech recognition, tinnitus, sound localization, and quality of life (QoL). A meta-analysis was performed, and pooled mean differences were calculated for each outcome of interest via random effects models by each outcome, as well as subgroup analyses by the individual clinical score used. RESULTS: Of 2309 studies identified, 185 full texts were evaluated, and 50 were ultimately included involving 674 patients. Speech perception scores in quiet and noise, tinnitus control, sound localization, and QoL all significantly improved after implantation. Pooled outcomes demonstrated score improvements in speech perception (standardized mean difference [SMD], 2.8 [95% CI, 2.16-3.43]), QoL (SMD, 0.68 [95% CI, 0.45-0.91]), sound localization (SMD, -1.13 [95% CI, -1.68 to -0.57]), and tinnitus score reduction (SMD, -1.32 [95% CI, -1.85 to -0.80]). CONCLUSIONS: Cochlear implantation in adults with SSD results in significant improvements in speech perception, tinnitus control, sound localization, and QoL.Level of evidence: 2.

Network Analysis of Neurobehavioral Symptom Patterns in an International Sample of Spanish-Speakers with a History of COVID-19 and Controls.

(1) Background: Psychometric network analysis provides a novel statistical approach allowing researchers to model clusters of related symptoms as a dynamic system. This study applied network analysis to investigate the patterns of somatic, cognitive, and affective neurobehavioral symptoms in an international sample of Spanish-speaking individuals with a history of COVID-19 positivity and non-COVID controls; (2) methods: the sample (n = 1093) included 650 adults from 26 countries who reported having previously tested positive for COVID-19 (COVID+) through a viral and/or antigen test (average of 147 days since diagnosis). The control group (COVID-) was comprised of 443 adults from 20 countries who had completed the survey prior to the COVID-19 pandemic; (3) results: relative to the COVID- network, the COVID+ network was very well-connected, such that each neurobehavioral symptom was positively connected to the network. The organize-to-headache and dizzy-to-balance connections in the COVID+ network were stronger than in the COVID- network. The hearing, numbness, and tense symptoms were more central to the COVID+ network with the latter connected to the sleep, fatigue, and frustrated symptoms. The COVID- network was largely disjointed, with most of the somatosensory symptoms forming their own cluster with no connections to other symptom groups and fatigue not being connected to any other symptom. The cognitive and affective symptoms in the COVID- network were also largely connected to symptoms from within their own groups; (4) conclusions: These findings suggest that many of the long-term neurobehavioral symptoms of COVID-19 form a discernable network and that headaches, frustration, hearing problems, forgetfulness, and tension are the most central symptoms. Cognitive and behavioral rehabilitation strategies targeting these central symptom network features may hold promise to help fracture the lingering symptom network of COVID-19.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Hybridization Chain Reaction Lateral Flow Assays for Amplified Instrument-Free At-Home SARS-CoV-2 Testing.

The lateral flow assay format enables rapid, instrument-free, at-home testing for SARS-CoV-2. Due to the absence of signal amplification, this simplicity comes at a cost in sensitivity. Here, we enhance sensitivity by developing an amplified lateral flow assay that incorporates isothermal, enzyme-free signal amplification based on the mechanism of hybridization chain reaction (HCR). The simplicity of the user experience is maintained using a disposable 3-channel lateral flow device to automatically deliver reagents to the test region in three successive stages without user interaction. To perform a test, the user loads the sample, closes the device, and reads the result by eye after 60 min. Detecting gamma-irradiated SARS-CoV-2 virions in a mixture of saliva and extraction buffer, the current amplified HCR lateral flow assay achieves a limit of detection of 200 copies/µL using available antibodies to target the SARS-CoV-2 nucleocapsid protein. By comparison, five commercial unamplified lateral flow assays that use proprietary antibodies exhibit limits of detection of 500 copies/µL, 1000 copies/µL, 2000 copies/µL, 2000 copies/µL, and 20,000 copies/µL. By swapping out antibody probes to target different pathogens, amplified HCR lateral flow assays offer a platform for simple, rapid, and sensitive at-home testing for infectious diseases. As an alternative to viral protein detection, we further introduce an HCR lateral flow assay for viral RNA detection.