Differential impact of COVID-19 non-pharmaceutical interventions on the epidemiological dynamics of respiratory syncytial virus subtypes A and B.

Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale; however, the cycling of RSV subtypes in the pre- and post-pandemic period remains poorly understood. Here, we used a two subtype RSV model supplemented with epidemiological data to study the impact of NPIs on the two circulating subtypes, RSV-A and RSV-B. The model is calibrated to historic RSV subtype data from the United Kingdom and Finland and predicts a tendency for RSV-A dominance over RSV-B immediately following the implementation of NPIs. Using a global genetic dataset, we confirm that RSV-A has prevailed over RSV-B in the post-pandemic period, consistent with a higher R0 for RSV-A. With new RSV infant monoclonals and maternal and elderly vaccines becoming widely available, these results may have important implications for understanding intervention effectiveness in the context of disrupted subtype dynamics.

Living on low-incomes with multiple long-term health conditions: A new method to explore the complex interaction between finance and health.

People on low-incomes in the UK develop multiple long-term health conditions over 10 years earlier than affluent individuals. Financial diaries -new to public health- are used to explore the lived experiences of financially-vulnerable individuals, diagnosed with at least one long-term condition, living in two inner-city London Boroughs. Findings show that the health status of these individuals is a key barrier to work opportunities, undermining their income. Their precarious and uncertain financial situation, sometimes combined with housing issues, increased stress and anxiety which, in turn, contributed to further deteriorate participants' health. Long-term health conditions limited the strategies to overcome moments of financial crisis and diarists frequently used credit to cope. Restrictions to access reliable services and timely support were connected to the progression of multiple long-term conditions. Models that integrate healthcare, public health, welfare and financial support are needed to slow down the progression from one to many long-term health conditions.

From polarity to plurality: Perceptions of COVID-19 and policy measures in England and Scotland.

AIM: The aim of this study was to uncover perspectives on the COVID-19 pandemic and the responses implemented by the UK and Scottish Governments to help control the spread of infection. Such understanding could help to inform future responses to pandemics at individual, community and national levels. METHOD: Q methodology was used to elicit perspectives from people in England and Scotland with different experiences of the pandemic including public health officials, key workers, those on furlough, those who were unvaccinated or vaccinated to different levels, those who were 'shielding' because they were at higher risk and people with different scientific expertise. Participants rank-ordered phrases about different aspects of COVID-19 according to their viewpoint. Factor analysis was then conducted in conjunction with interview material from the same respondents. RESULTS: A four-factor solution was statistically supported and was interpretable alongside the qualitative accounts of participants loading on these factors. These four perspectives are titled Dangerous and Unaccountable Leadership, Fear and Anger at Policy and Public responses, Governing Through a Crisis and Injustices Exposed. CONCLUSION: The four perspectives demonstrate plurality and nuance in views on COVID-19 and the associated policies and restrictions, going beyond a binary narrative that has been apparent in popular and social media. The four perspectives include some areas of common ground, as well as disagreement. We argue that understanding the detail of different perspectives might be used to build cohesion around policy initiatives in future. PATIENT OR PUBLIC CONTRIBUTION: The development of the statement set, which is rank-ordered by participants in a Q study, and factor interpretations were informed by views of the general public. The statement set was initially developed using existing publicly available material based on members of the general public experiencing the pandemic first hand. It was then piloted with members of the public experiencing different challenges as a result of COVID-19 and the subsequent lockdown and updated based on feedback. Finally, interpretations of the identified factors were presented publicly and edited according to their feedback.

Charting public views on the meaning of illness severity.

BACKGROUND: Illness severity is a central principle in multiple priority-setting frameworks, yet there is a paucity of research on public views regarding the meaning of illness severity. This study builds on the findings of a Q methodology study with members of the public that identified four general viewpoints on the meaning of illness severity. Here, we investigate the support for those viewpoints among the Norwegian population. METHODS: Following piloting, the online survey was distributed to a broadly representative sample of the population (March to April 2023). The viewpoints from the earlier Q study were converted into vignettes: Lifespan, Subjective, Objective, and Functioning and Quality of Life (FQoL). The main task in the survey comprised ranking the vignettes and scoring them on a 0-10 visual analogue scale. We describe vignette alignment (from weak to strong) based on four categorisations (C1 to C4). C1 placed all respondents on their top scored vignette(s); C2 required a score of ≥7; C3 was designed to resolve ties; and C4 (which describes vignette membership) required a score of ≥7, a gap of two between vignettes scored ≥7, and did not allow ties. RESULTS: The survey was completed by 1174 individuals; those who completed in ≤3.5 min were excluded. Of the final sample (n = 1094), 98.1% scored at least one vignette ≥7. In C1, 40.2% were aligned with Lifespan, 32.4% with FQoL, 28.9% with Objective, and 16.3% with Subjective. Using the C4 criteria, 55.4% did not have vignette membership, 13.6% had membership with Lifespan, 13.1% with Objective, 11.4% with FQoL, and 6.5% with Subjective. CONCLUSIONS: Severity is an ambiguous term among members of the public. Decisionmakers ought to bear this plurality of meanings in mind, and perhaps reconsider whether using a term as multifaceted as 'severity' is helpful in formulating precise and transparent priority-setting criteria.

Alarming Trends in Dengue Incidence and Mortality in Bangladesh.

Bangladesh is currently experiencing the country's largest and deadliest dengue outbreak on record. This year's outbreak has been characterized by an early seasonal surge in cases, rapid geographic spread, and a high fatality rate. The alarming trends in dengue incidence and mortality this year is an urgent wake-up call for public health policymakers and researchers to pay closer attention to dengue dynamics in South Asia, to strengthen the surveillance system and diagnostic capabilities, and to develop tools and methods for guiding strategic resource allocation and control efforts.

Modeling the impact of COVID-19 nonpharmaceutical interventions on respiratory syncytial virus transmission in South Africa.

Background: The South African government employed various nonpharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2. Surveillance data from South Africa indicates reduced circulation of respiratory syncytial virus (RSV) throughout the 2020-2021 seasons. Here, we use a mechanistic transmission model to project the rebound of RSV in the two subsequent seasons. Methods: We fit an age-structured epidemiological model to hospitalization data from national RSV surveillance in South Africa, allowing for time-varying reduction in RSV transmission during periods of COVID-19 circulation. We apply the model to project the rebound of RSV in the 2022 and 2023 seasons. Results: We projected an early and intense outbreak of RSV in April 2022, with an age shift to older infants (6-23 months old) experiencing a larger portion of severe disease burden than typical. In March 2022, government alerts were issued to prepare the hospital system for this potentially intense outbreak. We then assess the 2022 predictions and project the 2023 season. Model predictions for 2023 indicate that RSV activity has not fully returned to normal, with a projected early and moderately intense wave. We estimate that NPIs reduced RSV transmission between 15% and 50% during periods of COVID-19 circulation. Conclusions: A wide range of NPIs impacted the dynamics of the RSV outbreaks throughout 2020-2023 in regard to timing, magnitude, and age structure, with important implications in a low- and middle-income countries (LMICs) setting where RSV interventions remain limited. More efforts should focus on adapting RSV models to LMIC data to project the impact of upcoming medical interventions for this disease.

We need to talk about values: a proposed framework for the articulation of normative reasoning in health technology assessment.

It is acknowledged that health technology assessment (HTA) is an inherently value-based activity that makes use of normative reasoning alongside empirical evidence. But the language used to conceptualise and articulate HTA's normative aspects is demonstrably unnuanced, imprecise, and inconsistently employed, undermining transparency and preventing proper scrutiny of the rationales on which decisions are based. This paper - developed through a cross-disciplinary collaboration of 24 researchers with expertise in healthcare priority-setting - seeks to address this problem by offering a clear definition of key terms and distinguishing between the types of normative commitment invoked during HTA, thus providing a novel conceptual framework for the articulation of reasoning. Through application to a hypothetical case, it is illustrated how this framework can operate as a practical tool through which HTA practitioners and policymakers can enhance the transparency and coherence of their decision-making, while enabling others to hold them more easily to account. The framework is offered as a starting point for further discussion amongst those with a desire to enhance the legitimacy and fairness of HTA by facilitating practical public reasoning, in which decisions are made on behalf of the public, in public view, through a chain of reasoning that withstands ethical scrutiny.

Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease.

As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer-term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or 'evolution-proof') immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real-world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable and broadly protective vaccine.

Type 1 Diabetes Continuous Glucose Monitoring Use in the Pediatric Emergency Department Affects Laboratory Test Frequency but Not Treatment Timing.

Regular use of continuous glucose monitoring (CGM) in type 1 diabetes management increases the achievement of glycemic targets and reduces health care utilization, specifically emergency department (ED) visits. This retrospective chart review examined the effects of CGM use in patients with type 1 diabetes in a pediatric ED. Use of CGM was associated with several differences in patient management in the ED. This work is a first step toward development of guidelines for the appropriate use of CGM in the pediatric ED. In the future, CGM use in type 1 diabetes may lead to reduced ED-specific health care costs.

Developing a combined framework for priority setting in integrated health and social care systems.

BACKGROUND: There is an international move towards greater integration of health and social care to cope with the increasing demand on services.. In Scotland, legislation was passed in 2014 to integrate adult health and social care services resulting in the formation of 31 Health and Social Care Partnerships (HSCPs). Greater integration does not eliminate resource scarcity and the requirement to make (resource) allocation decisions to meet the needs of local populations. There are different perspectives on how to facilitate and improve priority setting in health and social care organisations with limited resources, but structured processes at the local level are still not widely implemented. This paper reports on work with new HSCPs in Scotland to develop a combined multi-disciplinary priority setting and resource allocation framework. METHODS: To develop the combined framework, a scoping review of the literature was conducted to determine the key principles and approaches to priority setting from economics, decision-analysis, ethics and law, and attempts to combine such approaches. Co-production of the combined framework involved a multi-disciplinary workshop including local, and national-level stakeholders and academics to discuss and gather their views. RESULTS: The key findings from the literature review and the stakeholder workshop were taken to produce a final combined framework for priority setting and resource allocation. This is underpinned by principles from economics (opportunity cost), decision science (good decisions), ethics (justice) and law (fair procedures). It outlines key stages in the priority setting process, including: framing the question, looking at current use of resources, defining options and criteria, evaluating options and criteria, and reviewing each stage. Each of these has further sub-stages and includes a focus on how the combined framework interacts with the consultation and involvement of patients, public and the wider staff. CONCLUSIONS: The integration agenda for health and social care is an opportunity to develop and implement a combined framework for setting priorities and allocating resources fairly to meet the needs of the population. A key aim of both integration and the combined framework is to facilitate the shifting of resources from acute services to the community.

Intravenous Fluid Resuscitation Capabilities in Simulated Reduced Gravity.

BACKGROUND: Critical care for exploration space missions may require intravenous (IV) fluid resuscitation therapy. Resource constraints may limit availability of standard, Earth-based infusion technologies. The effect of variable acceleration on infusion flow rates using simple fluid resuscitation supplies was investigated.METHODS: Infusions of water or blood analog (40% glycerol) from a 1 L IV bag were performed using pressure bag augmentation at 0, 150, or 300 mmHg. The solution bag rested on an adjustable mount, configured to different heights to simulate relevant gravitational accelerations (1 G, Martian G, lunar G, and 0 G). The bag emptied through an IV line with a 14- or 20-gauge angiocath into a 3-mmHg venous pressure reservoir. Flow rates were measured using an in-line flow probe. Three determinations were made for each test condition.RESULTS: Temporal flow rate data for all test conditions displayed one-phase exponential decay. At 300 mmHg pressurization, maximum infusion rates ranged from 92-222 mL ⋅ min-1 for water and from 21-49 mL ⋅ min-1 for blood analog. All reduced gravity conditions had significantly longer infusion times in comparison to 1 G for both test solutions.DISCUSSION: Reduced acceleration significantly altered flow rates and infusion times for fluid resuscitation. Fluid resuscitation protocols specify a desired volume to infuse for a target time (e.g., 20-30 mL ⋅ min-1 for a 75-kg adult). This data demonstrates that this protocol parameter can be achieved with infusion pressure bag augmentation alone and provides information for the refinement of fluid resuscitation protocols for exploration space missions.Pantalos GM, Heidel JS, Jain IM, Warner SE, Barefoot TL, Baker RO, Hailey M. Intravenous fluid resuscitation capabilities in simulated reduced gravity. Aerosp Med Hum Perform. 2023; 94(8):596-603.

Escape the Monotony: Gamification Enhances Nursing Education.

INTRODUCTION: Creating meaningful and engaging learning opportunities can be challenged by budgets, time, and learning management systems with limited methods of interaction. An innovative method was necessary to meet competency evaluation and continuing education needs for emergency department staff. DESIGN: Gamification and simulation techniques were combined to offer an interactive learning opportunity through an escape room format to improve engagement and knowledge retention. This educational offering was designed to enhance staff learning of trauma care and processes at emergency departments that are not designated trauma centers. OUTCOMES: Emergency department team members completed the trauma escape room challenge, and postsurvey results demonstrated favorable ratings of new knowledge acquisition, skill competency, teamwork, and confidence when providing care for a trauma patient. DISCUSSION: Nurse educators can "escape" the monotony of passive learning by using active learning strategies including the fun of gamification to improve clinical skills and confidence.

Discovery and Characterization of a Chemical Probe Targeting the Zinc-Finger Ubiquitin-Binding Domain of HDAC6.

Histone deacetylase 6 (HDAC6) inhibition is an attractive strategy for treating numerous cancers, and HDAC6 catalytic inhibitors are currently in clinical trials. The HDAC6 zinc-finger ubiquitin-binding domain (UBD) binds free C-terminal diglycine motifs of unanchored ubiquitin polymer chains and protein aggregates, playing an important role in autophagy and aggresome assembly. However, targeting this domain with small molecule antagonists remains an underdeveloped avenue of HDAC6-focused drug discovery. We report SGC-UBD253 (25), a chemical probe potently targeting HDAC6-UBD in vitro with selectivity over nine other UBDs, except for weak USP16 binding. In cells, 25 is an effective antagonist of HDAC6-UBD at 1 µM, with marked proteome-wide selectivity. We identified SGC-UBD253N (32), a methylated derivative of 25 that is 300-fold less active, serving as a negative control. Together, 25 and 32 could enable further exploration of the biological function of the HDAC6-UBD and investigation of the therapeutic potential of targeting this domain.

A severely fragmented concept: Uncovering citizens' subjective accounts of severity of illness.

Universal healthcare is constrained by national governments' finite health resources. This gives rise to complex priority-setting dilemmas. In several universal healthcare systems, the notion of severity (Norwegian: 'alvorlighet') is a key consideration in priority setting, such that treatments for 'severe' illness may be prioritised even when evidence suggests it would not be as cost-effective as treatment options for other conditions. However, severity is a poorly-defined concept, and there is no consensus on what severity means in the context of healthcare provision - whether viewed from public, academic, or professional perspectives. Though several public preference-elicitation studies demonstrate that severity is considered relevant in healthcare resource distribution, there is a paucity of research on public perceptions on the actual meaning of severity. We conducted a Q-methodology study between February 2021 and March 2022 to investigate views on severity amongst general public participants in Norway. Group interviews (n = 59) were conducted to gather statements for the Q-sort ranking exercises (n = 34). Data were analysed using by-person factor analysis to identify patterns in the statement rankings. We present a rich picture of perspectives on the term 'severity', and identify four different, partly conflicting, views on severity in the Norwegian population, with few areas of consensus. We argue that policymakers ought to be made aware of these differing perspectives on severity, and that there is need for further research on the prevalence of these views and on how they are distributed within populations.

Selective control of parasitic nematodes using bioactivated nematicides.

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amid limited arable land1-4. Most traditional nematicides have been banned owing to poor nematode selectivity, leaving farmers with inadequate means of pest control4-12. Here we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome-p450-mediated bioactivation in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita, a highly destructive plant-parasitic nematode. Tests against numerous phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than most marketed nematicides. Selectivins are first-in-class bioactivated nematode controls that provide efficacy and nematode selectivity.

From pipelines to pathways in the study of academic progress.

Students and administrators can benefit from new analytics.

Nemacol is a small molecule inhibitor of C. elegans vesicular acetylcholine transporter with anthelmintic potential.

Nematode parasites of humans and livestock pose a significant burden to human health, economic development, and food security. Anthelmintic drug resistance is widespread among parasites of livestock and many nematode parasites of humans lack effective treatments. Here, we present a nitrophenyl-piperazine scaffold that induces motor defects rapidly in the model nematode Caenorhabditis elegans. We call this scaffold Nemacol and show that it inhibits the vesicular acetylcholine transporter (VAChT), a target recognized by commercial animal and crop health groups as a viable anthelmintic target. We demonstrate that it is possible to create Nemacol analogs that maintain potent in vivo activity whilst lowering their affinity to the mammalian VAChT 10-fold. We also show that Nemacol enhances the ability of the anthelmintic Ivermectin to paralyze C. elegans and the ruminant nematode parasite Haemonchus contortus. Hence, Nemacol represents a promising new anthelmintic scaffold that acts through a validated anthelmintic target.

Skin Care for the Extremely Low-Birthweight Infant.

Extremely low-birthweight (ELBW) infants are at increased risk for infection because the innate immune function of their skin is underdeveloped as they lack a competent epidermal barrier. Thus, neonatal clinicians need to pay careful attention to skin care practices, particularly for periviable infants. In this review, we describe the challenges of skin care in ELBW infants and summarize strategies to prevent skin injury, minimize damage when it occurs, and enhance cutaneous innate immunity.