We are failing to improve the evidence base for “Exercise Referral”: How a Physical Activity Referral Scheme Taxonomy can help

Abstract not available

Physical activity for general health benefits in disabled children and disabled young people: rapid evidence review<strong> </strong>

Executive summary: Disabled children and disabled young people are at increased risk of being typically inactive, particularly as they become older. These issues have been exacerbated by the COVID-19 pandemic. This public health-focused report provides a review of the scientific evidence of the health benefits from physical activity, specifically for disabled children and disabled young people in non-clinical settings (aged 2 to 17 years). The research responds to a gap identified in the review of evidence for the 2019 UK Chief Medical Officers’ (CMOs’) physical activity guidelines. This important adjunct report enhances the comprehensiveness of the UK’s physical activity guidelines provision. It also provides future research recommendations. Furthermore, the report will also inform the first evidence-based infographic co-produced with disabled children and disabled young people, their parents and carers, health and social care professionals, and key disability and sport organisations to communicate meaningful messages about these physical activity recommendations, especially in relation to the frequency and duration of activity.There is evidence that shows a likely relationship between engaging in physical activity and positive health outcomes for disabled children and disabled young people. This report also provides suggestions about the amount (that is, frequency, duration and intensity) of physical activity that is likely to be important for disabled children and disabled young people to undertake to benefit their health. Some physical activity is better than nothing, as small amounts can bring health benefits. For likely substantial health gains, it is important for disabled children and disabled young people to do 120 to 180 minutes of mostly aerobic physical activity per week, at a moderate-to-vigorous intensity. The evidence suggests that this may be achieved in different ways (for example, 20 minutes per day or 40 minutes 3 times per week). It is also important for disabled children and disabled young people to do challenging strength and balance-focused activities on average 3 times per week. No evidence was found to show that physical activity is unsafe for disabled children and disabled young people when it is performed at an appropriate level for their current levels of physical development, fitness, physical and mental functioning (accounting for disability classification and severity), health and physical activity.This report provides evidence that aligns in part with the 2019 UK Chief Medical Officers’ physical activity guidelines for non-disabled children and disabled young people, as well as the 2020 guidelines published by the World Health Organization (WHO) for disabled children and disabled young people. However, there are also important differences in terms of recommended frequency and time. These are made based on the available evidence to provide recommendations specific to disabled children and disabled young people. The report also aids the communication and implementation of the guidelines by providing an evidence-base for disability groups, health and social care professionals, and sport and physical activity organisations to encourage physical activity to disabled children and disabled young people.The guidelines are the first to have included a review of evidence solely focused on disabled children and disabled young people’s physical activity, and thus represent the most comprehensive guidance globally

The same but different: Understanding entrepreneurial behaviour in disadvantaged communities

While entrepreneurship is widely viewed as being equally accessible in all contexts, it could be questioned if potential or nascent entrepreneurs from minority and disadvantaged communities experience entrepreneurship in a similar manner to the mainstream population. This chapter examines immigrant, people with disability, youth, gay and unemployed communities to explore how their entrepreneurial behaviour might differ from the practices of mainstream entrepreneurs. What emerges is that marginalised communities can frequently find it difficult to divorce business from social living. This can have both positive and negative connotations for an entrepreneur, plus they face additional and distinctive challenges that mainstream entrepreneurs do not experience. The chapter concludes by proposing a novel ‘funnel approach’ that policymakers might adopt when seeking to introduce initiatives targeted at these disadvantaged communities

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial

Background The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19. Methods This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing. Findings Between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8–9]) than participants in the placebo group (11 days [10–11]; HR 1·30, 95% credible interval 0·92–1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial. Interpretation We found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

The understanding, application and influence of complexity in national physical activity policy-making

Complexity theory and systems-thinking are increasingly popular in physical activity (PA) research and policy discourse. The impact of this perspective shift, across many sectors, may be underwhelming. We explore why, by focusing on how these concepts are understood and applied by PA policy-makers. This is of particular interest given the challenges of multisectoral interest and poorly defined stakeholder boundaries that are associated with PA promotion. In this study, we critique key elements of complexity theory and consider how it is understood and put into practice in PA policy-making. We adopted a complex realist position. Ten semi-structured interviews were conducted with national-level policy-makers from United Kingdom government settings (five civil servants, three politicians, two policy advisors). An inductive thematic analysis was conducted, and managed with NVivo 10 software. Three overarching themes were constructed to reflect policy-makers’ uncertainty about complexity and the application of such perspectives to this policy space, their sense that PA was an unexceptionable yet unclaimed policy issue, and their desire for influence and change. Participants discussed complexity in contrasting ways. Its meaning was context-dependent and dynamic, which generated uncertainty about applying the concept. Participants also perceived an increasingly diverse but ill-defined PA policy system that spans the domains of expertise and responsibility. Collaborative practices may contribute to a previously unobserved sense of detachment from the systems’ complexity. Nevertheless, participants suggested potentially effective ways to stimulate system change, which require passionate and enterprising leadership, and included varied evidence use, a focus on localised implementation and different ways to connect people. This research highlighted the importance of extending complexity theory and systems-thinking. While emphasizing the prevalence of these ideas across the PA sector, there is uncertainty as to their meaning and implications. This may prevent their use in ways that enhance PA policies and programmes. Participants conceptualised PA as a tool, which was imposed on the system. While this may support participative decision-making and localised implementation, further research is needed to understand how local systems foster leadership, the practical application of complexity and systems-thinking, and how to support system-wide change in the development and implementation of PA policies

Inequities and inequalities in outdoor walking groups: a scoping review

Background: Outdoor walking groups are widely-used programmes aimed at improving physical activity and health outcomes. Despite being promoted as accessible and inclusive, emerging work highlights participation biases based on gender, age and socioeconomic status, for example. To explicate the impact of outdoor walking groups on physical activity inequities, we conducted a scoping review of published outdoor walking group literatures. Specifically, we critically examined: (a) equity integration strategies; (b) intervention reach; (c) effectiveness; and (d) potential social determinants of engagement relating to the World Health Organization’s conceptual framework. Methods: Arksey and O’Malley’s scoping review protocol was used to develop a comprehensive search strategy and identify relevant academic and grey literatures, which were screened using pre-defined inclusion and exclusion criteria. Data were organised by Cochrane PROGRESS-Plus equity characteristics and a narrative summary was presented for each thematic area. Findings: Sixty-two publications were included. Key findings were: (a) some evidence of targeted intervention trials. Large-scale national programmes were tailored to regional activity and health needs, which may contribute toward addressing inequities. However, participant demographics seldom informed reported analyses; (b) participation was more likely among white, more socioeconomically advantaged, middle-to-older aged, female and able-bodied adults; (c) positive physical and psychological outcomes were unlikely to extend along social gradients; and (d) interventions primarily addressed intermediary determinants (e.g. psychosocial barriers; material resource). Social capital (e.g. friend-making) was identified as potentially important for addressing physical activity inequalities. Conclusions: The published literature on outdoor walking groups leaves unanswered questions regarding participation inequalities, with implications for future physical activity promotion. Currently, participation in outdoor walking groups is typically more prevalent among advantaged subpopulations. We make recommendations for research and practice to address these issues, as well as aid the translation of existing knowledge into practice. We advocate increased focus on the social determinants of engagement. A more consistent approach to collecting and analysing participant socio-demographic data is required. Our findings also support recommendations that appropriate tailoring of universal programmes to community needs and embedding strategies to increase social cohesion are important in developing equitable programmes