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IntroductionThe collection and evaluation of patient-reported outcomes is essential to the development of patient and family centered care. Current patient surveying techniques are limited by delayed response times and restriction to specific health systems. The use of random-domain intercept technology (RDIT), by Real-Time Interactive World-Wide Intelligence (RIWI, Toronto, ON, Canada) mitigates current barriers by creating a dynamic real-time feedback environment and providing a mass sampling technique.MethodsRDIT was employed to survey a wide sample of respondents across the United States (US). Respondents who self-identified as having had a surgical procedure or cared for someone having a surgical procedure were included in the analysis.Results1,004 participants completed the survey and answered questions regarding demographics, perioperative details, sentiments on postoperative recovery, postoperative clinical endpoints, sentiments on healthcare professionals, and opinions on future surgical care.DiscussionThe results of this cross-sectional study identified areas with potential for improvement in the patient perioperative experience that could improve the patient experience. This novel use of RDIT provided a valuable tool for real-time feedback and mass sampling allowing the creation of a dynamic healthcare environment that fosters timely and targeted improvements to patient experiences and outcomes.

Amanda L Neil,1 Vaughan J Carr2,3 1Menzies Institute for Medical Research, The University of Tasmania, Hobart, TAS, 2Research Unit for Schizophrenia Epidemiology, University of New South Wales, Sydney, NSW, 3Department of Psychiatry, School of Clinical Sciences, Monash University, Melbourne, VIC, AustraliaFor clarification, we undertook bottom-up costing using individual participant data from the Low Prevalence Disorders Study in our costing study.1 We did not use the data reported in the study by Carr et al2 as asserted by Chong et al.3 Chong et al have thus misunderstood and thus misrepresented our methodology in both their systematic review4 and their response to our letter.5 Authors' reply Huey Yi Chong,1 Nathorn Chaiyakunapruk1–41School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 2Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 3School of Pharmacy, University of Wisconsin, Madison, USA; 4School of Population Health, University of Queensland, Brisbane, Australia We thank Dr Neil and Professor Carr for their clarification on the data source used in their study.1 In this regard, we would like to highlight one of the most common challenges when conducting any systematic review, for example economic burden of schizophrenia in this case – the marked diversity in reporting among the included studies, which increases the likelihood of any potential misinterpretation. In convergence with a number of published systematic reviews of economic burden studies,2–5 there has been a consistent call for a more explicit reporting in various aspects of an economic burden study, thus readability and transparency can be enhanced. However, a standardized guide/checklist for conducting and reporting economic burden is yet to be available. On the final note, we strongly urge for the development of such a guidance document to improve the quality and clarity of an economic burden study. View original paper by Chong et al View original Letter by Neil and Carr

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.

Hoy en día, los derrames de petróleo no son casos aislados. El uso en gran medida de hidrocarburos genera altas tasas de probabilidades de derrames. Lamentablemente, el Perú no es la excepción en la incidencia de derrames de petróleo. Ante estos eventos la biorremediación con microorganismos marinos (bacterias y cianobacterias) surge como una solución sostenible para implementar planes de contingencia ante potenciales acontecimientos de contaminación por hidrocarburos. Entre las bacterias más importantes resaltan los géneros Achromobacter, Acinetobacter y Pseudomonas, Alteromonas, Haloferula, Ruegeria y Alcanivorax. Asimismo, bacterias nativas peruanas como Vibrio fluvialis y Vibrio sp. y la cianobacteria Anabaena cicadae han mostrado potencial de biodegradación. Es imperativo que las autoridades promuevan la investigación sobre el uso de consorcios microbianos autóctonos en ambientes naturales en adición de nutrientes, en diferentes estratos y zonificación de la costa peruana.

Proponer estrategias para mejorar la capacidad de respuesta de los pescadores artesanales ante derrames de petróleo, basándonos en experiencias exitosas internacionales, se hace indispensable en el Perú. Esto se vuelve más importante recordando lo acontecido el 15 de enero de 2022, donde cerca de 11 000 barriles de petróleo fueron derramados al mar frente a la Refinería La Pampilla. Resulta fundamental facultar a los pescadores en técnicas de monitoreo y respuesta, dotarlos de equipos adecuados, e implementar sistemas de alerta temprana. Es fundamental crear redes de vigilancia comunitaria y fortalecer el marco legal para incluir la participación de estas comunidades. La cooperación internacional es fundamental para intercambiar conocimientos y mejores prácticas. Estas acciones buscan minimizar los impactos ambientales y socioeconómicos de los derrames de petróleo, al empoderar a las comunidades locales y promover una gestión sostenible del entorno marino.

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of cases. CCHFV is listed as a priority pathogen by the World Health Organization (WHO) and there are currently no widely-approved vaccines. Defining a serological correlate of protection against CCHFV infection would support the development of vaccines by providing a ‘target threshold’ for pre-clinical and clinical immunogenicity studies to achieve in subjects and potentially obviate the need for in vivo protection studies. We therefore sought to establish titratable protection against CCHFV using pooled human convalescent plasma, in a mouse model. Convalescent plasma collected from seven individuals with a known previous CCHFV virus infection were characterised using binding antibody and neutralisation assays. All plasma recognised nucleoprotein and the Gc glycoprotein, but some had a lower Gn glycoprotein response by ELISA. Pooled plasma and two individual donations from convalescent donors were administered intraperitoneally to A129 mice 24 h prior to intradermal challenge with CCHFV (strain IbAr10200). A partial protective effect was observed with all three convalescent plasmas characterised by longer survival post-challenge and reduced clinical score. These protective responses were titratable. Further characterisation of the serological reactivities within these samples will establish their value as reference materials to support assay harmonisation and accelerate vaccine development for CCHFV.

BackgroundDuring an infodemic, timely, reliable, and accessible information is crucial to combat the proliferation of health misinformation. While message testing can provide vital information to make data-informed decisions, traditional methods tend to be time- and resource-intensive. Recognizing this need, we developed the rapid message testing at scale (RMTS) approach to allow communicators to repurpose existing social media advertising tools and understand the full spectrum of audience engagement. ObjectiveWe had two main objectives: (1) to demonstrate the use of the RMTS approach for message testing, especially when resources and time are limited, and (2) to propose and test the efficacy of an outcome variable that measures engagement along a continuum of viewing experience. MethodsWe developed 12 versions of a single video created for a vaccine confidence project in India. We manipulated video length, aspect ratio, and use of subtitles. The videos were tested across 4 demographic groups (women or men, younger or older). We assessed user engagement along a continuum of viewing experience: obtaining attention, sustaining attention, conveying the message, and inspiring action. These were measured by the percentage of video watched and clicks on the call-to-action link. ResultsThe video advertisements were placed on Facebook for over 4 consecutive days at the cost of US $450 and garnered a total of 3.34 million impressions. Overall, we found that the best-performing video was the shorter version in portrait aspect ratio and without subtitles. There was a significant but small association between the length of the video and users’ level of engagement at key points along the continuum of viewing experience (N=1,032,888; χ24=48,261.97; P

Objective: To report a case of mandibular fracture in a newborn presenting with post-delivery oral cavity bleeding and to discuss its etiology, clinical findings, diagnosis, management and outcome after treatment. Methods: Design: Case Report Setting: Tertiary Government Training Hospital Patient: One Results: A newborn girl was referred for oral cavity bleeding after partial breech extraction. An intraoral hematoma and symphyseal step deformity on examination corresponded to a complete fracture of the symphysis and downward displacement of the left hemimandible on facial CT scans with 3D reconstruction. An uneventful closed reduction with external fixation using acrylic cap splint with circum-mandibular wiring was performed under general anesthesia and she was discharged feeding well. The cap splint and wires were removed after 4 weeks showing good facial symmetry and bone alignment. There were no complications on follow-up after 1 year. Conclusion: Mandibular fracture can result from traumatic delivery and present with oral bleeding and hematoma. A thorough physical examination and workup should be done to assess for the sites involved. A multidisciplinary approach should be undertaken to provide the best possible care with the least invasive technique.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing a debilitating febrile illness with rheumatic disease symptoms of arthralgia and arthritis. Since its spread outside of Africa in 2005, it continues to cause outbreaks and disseminates into new territories. Intervention strategies are urgently required, including vaccination and antiviral approaches. To test efficacy, the use of small animal models is required. Two mouse strains, A129, with a deficiency in their type-I interferon (IFN) receptor, and C57BL/6 are widely used. A direct comparison of these strains alongside the wild-type parental strain of the A129 mice, 129Sv/Ev, was undertaken to assess clinical disease progression, viral loads in key tissues, histological changes and levels of sera biomarkers. Our results confirm the severe disease course in A129 mice which was not observed in the parental 129Sv/Ev strain. Of the two wild-type strains, viral loads were higher in 129Sv/Ev mice compared to C57BL/6 counterparts. Our results have established these models and parameters for the future testing of vaccines and antiviral approaches.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family.

Abstract India has reported more than 35 million confirmed cases of COVID-19 and nearly half a million cumulative deaths. Although vaccination rates for the first vaccine dose are quite high, one-third of the population has not received a second shot. Due to its widespread use and popularity, social media can play a vital role in enhancing vaccine acceptance. This study in a real-world setting utilizes YouTube videos in Odisha, India where the platform has deep penetration among the 18–35 target population, and secondarily their family and peers. Two contrasting videos were launched on the YouTube platform to examine how those videos operate within the broader recommender and subscription systems that determine the audience reach. Video analytics, algorithms for recommended videos, visual representation of connections created, centrality between the networks, and comment analysis was conducted. The results indicate that the video with a non-humorous tone and collectivistic appeal delivered by a female protagonist performed best with regard to views and time spent watching the videos. The results are of significance to health communicators who seek to better understand the platform mechanisms that determine the spread of videos and measures of viewer reactions based on viewer sentiment.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation. Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke–induced airway inflammation in humans. Methods: This was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol–enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates. Results: Short-course γ-tocopherol intervention did not reduce wood smoke–induced neutrophilic airway inflammation, but it did prevent wood smoke–induced eosinophilic airway inflammation. Conclusion: γ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.

Abstract Background Cross-cultural communication, often conceptualized along culture and language dimensions, is an important issue for collaborative teams that include both scientists and artists. Such teams must balance the standardization needs of rigorous scientific methods, on the one hand, with openness for artistic creativity, on the other. The scientific literature does not provide clear guidance on how to structure such collaborations. Discussion We created eight videos manipulating the type of appeal, message tone, and gender of the vaccine promoter in a 2 × 2 × 2 between-subjects experiment. The four stages of the filmmaking process were 1) conceptualizing filmmaking and script writing through a scientific lens, 2) pilot testing and finalizing the script, 3) video production and editing, and 4) dissemination. We describe the process and learnings from a collaboration that included filmmakers, researchers, and vaccine experts from India and the United States in producing, disseminating, and evaluating videos that promoted vaccine uptake in Odisha, India. Conclusions When projects require close collaborations between scientists and artists, committing to a unified vision is essential for facilitating open, bidirectional communication and building trust between the partners. Clearly denoting research boundaries ensures that the scientific needs of the project are met while simultaneously welcoming space for the filmmakers’ creativity, fostering a sense of ownership, and enhancing the final product.

Abstract SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species—one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters—following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10–28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.

Abstract Background Benzodiazepines (BZD) are widely prescribed to older adults despite their association with increased fall injury. Our aim is to better characterize risk-elevating factors among those prescribed BZD. Methods A retrospective cohort study using a 20% sample of Medicare beneficiaries with Part D prescription drug coverage. Patients with a BZD prescription (“index”) between 1 April 2016 and 31 December 2017 contributed to incident (n=379,273) and continuing (n=509,634) cohorts based on prescriptions during a 6-month pre-index baseline. Exposures were index BZD average daily dose and days prescribed; baseline BZD medication possession ratio (MPR) (for the continuing cohort); and co-prescribed central nervous system-active medications. Outcome was a treated fall-related injury within 30 days post-index BZD, examined using Cox proportional hazards adjusting for demographic and clinical covariates and the dose prescribed. Results Among incident and continuing cohorts, 0.9% and 0.7% experienced fall injury within 30 days of index. In both cohorts, injury risk was elevated immediately post-index among those prescribed the lowest quantity: e.g., for

Understanding infectious disease pathogenesis and evaluating novel candidate treatment interventions for human use frequently requires prior or parallel analysis in animal model systems. While rodent species are frequently applied in such studies, there are situations where non-human primate (NHP) species are advantageous or required. These include studies of animals that are anatomically more akin to humans, where there is a need to interrogate the complexity of more advanced biological systems or simply reflect susceptibility to a specific infectious agent. The contribution of different arms of the immune response may be addressed in a variety of NHP species or subspecies in specific physiological compartments. Such studies provide insights into immune repertoires not always possible from human studies. However, genetic variation in outbred NHP models may confound, or significantly impact the outcome of a particular study. Thus, host factors need to be considered when undertaking such studies. Considerable knowledge of the impact of host immunogenetics on infection dynamics was elucidated from HIV/SIV research. NHP models are now important for studies of emerging infections. They have contributed to delineating the pathogenesis of SARS-CoV-2/COVID-19, which identified differences in outcomes attributable to the selected NHP host. Moreover, their use was crucial in evaluating the immunogenicity and efficacy of vaccines against COVID-19 and establishing putative correlates of vaccine protection. More broadly, neglected or highly pathogenic emerging or re-emergent viruses may be studied in selected NHPs. These studies characterise protective immune responses following infection or the administration of candidate immunogens which may be central to the accelerated licensing of new vaccines. Here, we review selected aspects of host immunogenetics, specifically MHC background and TRIM5 polymorphism as exemplars of adaptive and innate immunity, in commonly used Old and New World host species. Understanding this variation within and between NHP species will ensure that this valuable laboratory source is used most effectively to combat established and emerging virus infections and improve human health worldwide.

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.

Background Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions.Methods Malaria cases for 2011—2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts.Results Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p

ABSTRACT Objective: To report a case of multifocal pediatric tuberculosis presenting with mandibular swelling and discuss its etiology, clinical findings, diagnosis, management, and outcome after treatment. Methods: Design: Case Report Setting: Tertiary Government Training Hospital Patient: One Results: A 3-year-old boy presented with progressive non-tender, right mandibular swelling for 11 months. Panoramic X-ray exhibited extensive multiple loculations with lytic changes on the mandible. CT Scans revealed a peripherally enhancing hypodense mass with lytic expansion of the right mandibular angle extending across the left mandibular body with an incidental finding of right lung mass. Other extrapulmonary lesions were also detected involving the scapula, pleura with lysis of the adjacent ribs at the level of T7 and T8. Biopsy of the mandibular and lung mass confirmed the presence of caseating and non-caseating granulomas consistent with Koch’s infection. The patient showed significant improvement by the 7th month of a 12-month course of anti-tuberculous therapy. Conclusion: Multifocal TB can present as simple mandibular swelling, and a thorough workup should look for other involved sites. Early diagnosis in children may prevent debilitating sequelae and improve long-term treatment outcomes.

Tuberculosis (TB) remains the second leading cause of death globally from a single infectious agent, and there is a critical need to develop improved imaging biomarkers and aid rapid assessments of responses to therapy. We aimed to utilize radiomics, a rapidly developing image analysis tool, to develop a scoring system for this purpose. A chest X-ray radiomics score (RadScore) was developed by implementing a unique segmentation method, followed by feature extraction and parameter map construction. Signature parameter maps that showed a high correlation to lung pathology were consolidated into four frequency bins to obtain the RadScore. A clinical score (TBscore) and a radiological score (RLscore) were also developed based on existing scoring algorithms. The correlation between the change in the three scores, calculated from serial X-rays taken while patients received TB therapy, was evaluated using Spearman’s correlation. Poor correlations were observed between the changes in the TBscore and the RLscore (0.09 (p-value = 0.36)) and the TBscore and the RadScore (0.02 (p-value = 0.86)). The changes in the RLscore and the RadScore had a much stronger correlation of 0.22, which is statistically significant (p-value = 0.02). This shows that the developed RadScore has the potential to be a quantitative monitoring tool for responses to therapy.

Background: Vaccine hesitancy is one of the greatest challenges to the success of coronavirus disease 2019 (COVID-19) vaccination campaigns. Videos promoting vaccines have a narrow scope focusing solely on facts, and less on the emotional and narrative elements of communication that can be equally persuasive. The role of humor, for example, has remained largely unexplored. Objective: This study investigates whether theory-based videos can change people’s attitudes, beliefs, and intentions to receive the second COVID-19 vaccine. Our primary research question is: How do collectivistic and individualistic appeals, humor, and protagonist gender individually and jointly affect vaccination attitudes, beliefs, and intentions? Methods: This project tapped into the underutilized Indian film industry—the world’s largest film producer—to promote vaccination messaging through short videos. Feedback from a community advisory board was utilized to inform the video scripts that were then shot by a production team. Eight videos were filmed and shared by adopting a 2 (appeal: individualistic or collectivistic) x 2 (tone: humor or non-humor) x 2 (protagonist gender: male or female) between-subjects design approach. Our sample includes Odia-speaking participants aged between 18 – 35 years old randomly assigned to watch one of the eight study videos. An online survey questionnaire, social media network analysis, and small group qualitative interviews will be utilized to explore how the entertainment-education videos can be used to reduce vaccine hesitancy. Discussion: Vaccine messages do not fall into a cultural or cognitive vacuum. People process and make sense of information based on their prior experience, properties of the message, and their social environment. Yet, these considerations have taken secondary importance in vaccine communications. This research shows that it is possible to deliver high-caliber videos created in accordance with the audience's cultural and cognitive background. Conclusions: This study will inform future health promotion messaging through brief videos on the internet.