External evaluation of the Represent programme: report for the National Literacy Trust

NLT’s Represent programme aimed to address the comparatively lower chances of educational achievement of excluded girls and their greater vulnerability to exploitation, grooming, violence, or engaging in criminal behaviour. Excluded girls often have chaotic lives, live in poverty and are less likely to have access to professionals that might provide the stability and support required for sustained engagement with positive role models1. In total, 265 education settings registered their interest in delivering the Represent programme with NLT and received the resource pack required for delivering sessions for 368 groups of students. Of these, at least 822 schools participated in one or more aspects of the evaluation project. The evaluation of the Represent programme sets out to understand five key questions using a mixed-methods approach to explore the complexities of the girls’ experiences, and how the programme has helped to connect the problems around attendance with pathways to future capabilities and wellbeing

Proportionate methods for evaluating a simple digital mental health tool

Background: Traditional evaluation methods are not keeping pace with rapid developments in mobile health. More flexible methodologies are needed to evaluate mHealth technologies, particularly simple, self-help tools. One approach is to combine a variety of methods and data to build a comprehensive picture of how a technology is used and its impact on users. Objective: This paper aims to demonstrate how analytical data and user feedback can be triangulated to provide a proportionate and practical approach to the evaluation of a mental wellbeing smartphone app (‘In Hand’). Methods: A three-part process was used to collect data: 1) app analytics; 2) an online user survey; and 3) interviews with users. Findings: Analytics showed that >50% of user sessions counted as ‘meaningful engagement’. User survey findings (N=108) revealed that In Hand was perceived to be helpful on several dimensions of mental wellbeing. Interviews (N=8) provided insight into how these self-reported positive effects were understood by users. Conclusions: This evaluation demonstrates how different methods can be combined to complete a real-world, naturalistic evaluation of a self-help digital tool and provide insights into how and why an app is used and its impact upon users’ wellbeing. Clinical implications: This triangulation approach to evaluation provides insight into how wellbeing apps are used and their perceived impact on users’ mental wellbeing. This approach is useful for mental healthcare professionals and commissioners who wish to recommend simple digital tools to their patients and evaluate their uptake, use and benefits

Myths and Methodologies:Standardisation in human physiology research—should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants’ habitual diets, yet a self‐report and replication method can be flawed by under‐reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash‐out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between‐ or within‐participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts

Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

SummaryBackground Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity,preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the otherRECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses weredone on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN,50189673, and ClinicalTrials.gov, NCT04381936.Findings Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Resultswere consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092).Interpretation In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19.Funding Medical Research Council and National Institute for Health Research

The UKC2 regional coupled environmental prediction system

It is hypothesized that more accurate prediction and warning of natural hazards, such as of the impacts of severe weather mediated through various components of the environment, require a more integrated Earth System approach to forecasting. This hypothesis can be explored using regional coupled prediction systems, in which the known interactions and feedbacks between different physical and biogeochemical components of the environment across sky, sea and land can be simulated. Such systems are becoming increasingly common research tools. This paper describes the development of the UKC2 regional coupled research system, which has been delivered under the UK Environmental Prediction Prototype project. This provides the first implementation of an atmosphere–land–ocean–wave modelling system focussed on the United Kingdom and surrounding seas at km-scale resolution. The UKC2 coupled system incorporates models of the atmosphere (Met Office Unified Model), land surface with river routing (JULES), shelf-sea ocean (NEMO) and ocean waves (WAVEWATCH III). These components are coupled, via OASIS3-MCT libraries, at unprecedentedly high resolution across the UK within a north-western European regional domain. A research framework has been established to explore the representation of feedback processes in coupled and uncoupled modes, providing a new research tool for UK environmental science. This paper documents the technical design and implementation of UKC2, along with the associated evaluation framework. An analysis of new results comparing the output of the coupled UKC2 system with relevant forced control simulations for six contrasting case studies of 5-day duration is presented. Results demonstrate that performance can be achieved with the UKC2 system that is at least comparable to its component control simulations. For some cases, improvements in air temperature, sea surface temperature, wind speed, significant wave height and mean wave period highlight the potential benefits of coupling between environmental model components. Results also illustrate that the coupling itself is not sufficient to address all known model issues. Priorities for future development of the UK Environmental Prediction framework and component systems are discussed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease

Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. // Methods and analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial. // Ethics and dissemination: Ethical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals. // Trial registration number: ISRCTN30448031; EudraCT number: 2021-005748-31

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem