A response to the House of Commons Education Committee report on Multi-Academy Trusts

The number of schools joining multi-academy trusts has grown over the last five years, and it is expected that this growth will continue. The House of Commons Education Committee has, as a result, looked into the performance and role of these trusts. Steven J Courtney, Ruth McGinity, Steven Jones, Robert Hindle, Stephen M Rayner and Belinda Hughes focus on four key aspects of the Committee’s report and argue that broader questions about the government’s policy remain untouched

Support to Continue Studying: Greater Manchester Mental Health in Further Education Evaluation Final Report

This evaluation was commissioned by the Association of Colleges to consider the impacts of the Greater Manchester Mental Health in Further Education project on the experience of learners, staff and strategic working. The evaluation consists of two phases and was conducted by York St John University’s Converge Evaluation and Team – a group of researchers with lived experience of mental health challenges that share insight through experience. This report shares findings from Phase 2 drawing on interviews with staff across a range of roles and colleges, workshops with learners, an online survey and existing project data. A primarily qualitative approach was used to gather narratives of the project’s impact and distance travelled from the perspective of those involved. For Phase 1 findings see the interim report

Self-esteem, self-efficacy and optimism as psychological resources among family caregivers of people with dementia: findings from the IDEAL study

YesBeing a family caregiver, and in particular giving care to someone with dementia, impacts upon mental and physical health, and potentially reduces the ability of caregivers to ‘live well’. This paper examines whether three key psychological resources, self-efficacy, optimism and self-esteem, are associated with better outcomes for caregivers of people with dementia. Design and Participants Caregivers of 1283 people with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) project responded to measures of selfefficacy, optimism and self-esteem, and ‘living well’ (quality of life, life satisfaction and well-being). Multivariate linear regression was used to examine the association between psychological resources and ‘living well’. Results Self-efficacy, optimism and self-esteem were all independently associated with better capability to ‘live well’ for caregivers. This association persisted when accounting for a number of potential confounding variables (age group, sex, and hours of caregiving per day). Conclusions Low self-efficacy, optimism and self-esteem might present a risk of poor outcomes for caregivers of people with dementia. These findings encourage us to consider how new or established interventions might increase the psychological resilience of caregivers

A comprehensive model of factors associated with subjective perceptions of living well with dementia: findings from the IDEAL study

Background: The concept of ‘living well’ is increasingly used to indicate that it is, or should be, possible for a person living with dementia to experience a subjective sense of ‘comfort, function and contentment with life.’ We used a theoretically-derived conceptual framework to investigate capability to ‘live well’ with dementia through identifying the relative contribution of domains associated with the subjective experience of living well. Methods: We analysed data from 1550 community-dwelling individuals with mild to moderate dementia participating in the baseline wave of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study. Subjective perceptions of ability to live well were obtained by generating a living well latent factor from responses on the Quality of Life in Alzheimer’s disease (QoL-AD), Satisfaction with Life and WHO-5 Well-being scales. Multivariate modelling and structural equation modelling was used to investigate variables potentially associated with living well. Variables were grouped into five domains, latent variables were constructed representing Social Location, Capitals, Assets and Resources, Psychological Characteristics and Psychological Health, Physical Fitness and Health, and Managing Everyday Life with Dementia, and associations with living well were examined. All models were adjusted for age, sex and dementia sub-type. Results: Considering the domains singly, the Psychological Characteristics and Psychological Health domain was most strongly associated with living well (3.56; 95% CI: 2.25, 4.88), followed by Physical Fitness and Physical Health (1.10, 95% CI: -2.26, 4.47). Effect sizes were smaller for Capitals, Assets and Resources (0.53; 95% CI: -0.66, 1.73), Managing Everyday Life with Dementia (0.34; 95% CI: 0.20, 0.87), and Social Location (-0.12; 95% CI: -5.72, 5.47). Following adjustment for the Psychological Characteristics and Psychological Health domain, other domains did not show independent associations with living well. Conclusions: Psychological resources are central to subjective perceptions of living well and offer important targets for immediate intervention. Availability of social and environmental resources, and physical fitness, underpin these positive psychological states, and also offer potential targets for interventions and initiatives aimed at improving the experience of living with dementia

A comprehensive model of factors associated with subjective perceptions of living well with dementia: findings from the IDEAL study

Background: The concept of ‘living well’ is increasingly used to indicate that it is, or should be, possible for a person living with dementia to experience a subjective sense of ‘comfort, function and contentment with life.’ We used a theoretically-derived conceptual framework to investigate capability to ‘live well’ with dementia through identifying the relative contribution of domains associated with the subjective experience of living well. Methods: We analysed data from 1550 community-dwelling individuals with mild to moderate dementia participating in the baseline wave of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study. Subjective perceptions of ability to live well were obtained by generating a living well latent factor from responses on the Quality of Life in Alzheimer’s disease (QoL-AD), Satisfaction with Life and WHO-5 Well-being scales. Multivariate modelling and structural equation modelling was used to investigate variables potentially associated with living well. Variables were grouped into five domains, latent variables were constructed representing Social Location, Capitals, Assets and Resources, Psychological Characteristics and Psychological Health, Physical Fitness and Health, and Managing Everyday Life with Dementia, and associations with living well were examined. All models were adjusted for age, sex and dementia sub-type. Results: Considering the domains singly, the Psychological Characteristics and Psychological Health domain was most strongly associated with living well (3.56; 95% CI: 2.25, 4.88), followed by Physical Fitness and Physical Health (1.10, 95% CI: -2.26, 4.47). Effect sizes were smaller for Capitals, Assets and Resources (0.53; 95% CI: -0.66, 1.73), Managing Everyday Life with Dementia (0.34; 95% CI: 0.20, 0.87), and Social Location (-0.12; 95% CI: -5.72, 5.47). Following adjustment for the Psychological Characteristics and Psychological Health domain, other domains did not show independent associations with living well. Conclusions: Psychological resources are central to subjective perceptions of living well and offer important targets for immediate intervention. Availability of social and environmental resources, and physical fitness, underpin these positive psychological states, and also offer potential targets for interventions and initiatives aimed at improving the experience of living with dementia

Protocol for the IDEAL-2 longitudinal study: Following the experiences of people with dementia and their primary carers to understand what contributes to living well with dementia and enhances active life

Background There is a major need for longitudinal research examining the experiences of people with dementia and their primary carers, as relatively little is known about how the factors associated with capability to ‘live well’ vary over time. The main aim of the IDEAL-2 study is to investigate how and why, over time, people with dementia and their primary carers might vary in their capability to live well with dementia, whilst exploring both their use of health and care services and their unmet needs. Methods IDEAL-2 will build on the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort of 1547 people (who, at recruitment between July 2014 and July 2016, had mild-to-moderate dementia), and their 1283 primary carers in Great Britain. The existing cohort will be enriched with additional participants with mild-to-moderate dementia (and their primary carers where available and willing) from the following groups: people with rarer forms of dementia, and/or those who are ≥90 years or < 65 years of age at time of recruitment. We will assess the primary outcome, capability to live well with dementia, and the factors influencing it using questionnaires at yearly intervals for 3 years. Additionally, we will seek to link the cohort data with administrative data to obtain information about health service use. Some participants will be invited for in-depth face-to-face interviews. The cohort study will be supplemented by linked research focusing on: the co-production of new measures of living well; including the perspectives of people with advanced dementia living in residential care settings; including people with dementia from black, Asian, and minority ethnic groups; and understanding the experience of people living with undiagnosed dementia. Discussion IDEAL-2 will provide evidence about the key indicators of, and factors associated with, living well over the course of dementia and how these differ for particular subgroups. It will tell us which combinations of services and support are most beneficial and cost-effective. Moreover, the IDEAL-2 study will gather evidence from under-researched groups of people with dementia, who are likely to have their own distinct perceptions of living well.Alzheimer’s Society & The University of Exete

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570