Uptake of self-management education programmes for people with type 2 diabetes in primary care through the embedding package: a cluster randomised control trial and ethnographic study.

BACKGROUND: Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. METHODS: Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. 'Embedders' supported practices and self-management programme providers to embed programme referral into routine practice, and an online 'toolkit' contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months - 3-0), step one (months 1-9), step 2 (months 10-18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. RESULTS: No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p < 0.001), and higher self-management programme attendance (adjusted odds ratio: 1.13; 95% confidence interval: 1.02, 1.25; p = 0.017) during intervention conditions. Themes identified through the ethnographic study included challenges for Embedders in making and sustaining contact with practices and providers, and around practices' interactions with the toolkit. CONCLUSIONS: Barriers to implementing the Embedding Package may have compromised its effectiveness. Statistically but not clinically significantly improved HbA1c among ethnic minority groups and in longer-term follow-up suggest that future research exploring methods of embedding diabetes self-management programmes into routine care is warranted. TRIAL REGISTRATION: ISRCTN23474120, registered 05/04/2018.

Incorporating polygenic risk into the Leicester Risk Assessment score for 10-year risk prediction of type 2 diabetes.

AIMS: We evaluated whether incorporating information on ethnic background and polygenic risk enhanced the Leicester Risk Assessment (LRA) score for predicting 10-year risk of type 2 diabetes. METHODS: The sample included 202,529 UK Biobank participants aged 40-69 years. We computed the LRA score, and developed two new risk scores using training data (80% sample): LRArev, which incorporated additional information on ethnic background, and LRAprs, which incorporated polygenic risk for type 2 diabetes. We assessed discriminative and reclassification performance in a test set (20% sample). Type 2 diabetes was ascertained using primary care, hospital inpatient and death registry records. RESULTS: Over 10 years, 7,476 participants developed type 2 diabetes. The Harrell's C indexes were 0.796 (95% Confidence Interval [CI] 0.785, 0.806), 0.802 (95% CI 0.792, 0.813), and 0.829 (95% CI 0.820, 0.839) for the LRA, LRArev and LRAprs scores, respectively. The LRAprs score significantly improved the overall reclassification compared to the LRA (net reclassification index [NRI] = 0.033, 95% CI 0.015, 0.049) and LRArev (NRI = 0.040, 95% CI 0.024, 0.055) scores. CONCLUSIONS: Polygenic risk moderately improved the performance of the existing LRA score for 10-year risk prediction of type 2 diabetes.

Impact of the COVID-19 pandemic on hospital episodes for falls and fractures associated with new-onset disability and frailty in England: a national cohort study.

BACKGROUND: Older people with frailty are at risk of harm from immobility or isolation, yet data about how COVID-19 lockdowns affected them are limited. Falls and fractures are easily measurable adverse outcomes correlated with frailty. We investigated whether English hospital admission rates for falls and fractures varied from the expected trajectory during the COVID-19 pandemic, and how these varied by frailty status. METHODS: NHS England Hospital Episode Statistics Admitted Patient Care data were analysed for observed versus predicted outcome rates for 24 January 2020 to 31 December 2021. An auto-regressive integrated moving average time-series model was trained using falls and fracture incidence data from 2013 to 2018 and validated using data from 2019. Models included national and age-, sex- and region-stratified forecasts. Outcome measures were hospital admissions for falls, fractures, and falls and fractures combined. Frailty was defined using the Hospital Frailty Risk Score. RESULTS: 144,148,915 pre-pandemic hospital admissions were compared with 42,267,318 admissions after pandemic onset. For the whole population, falls and fracture rates were below predicted for the first period of national lockdown, followed by a rapid return to rates close to predicted. Thereafter, rates followed expected trends. For people living with frailty, however, falls and fractures increased above expected rates during periods of national lockdown and remained elevated throughout the study period. Effects of frailty were independent of age. CONCLUSIONS: People living with frailty experienced increased fall and fracture rates above expected during and following periods of national lockdown. These remained persistently elevated throughout the study period.

Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.

INTRODUCTION: Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D. MATERIALS AND METHODS: We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective. RESULTS: Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years. CONCLUSIONS: We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect. TRIAL REGISTRATION NUMBER: ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

The Effectiveness of Lifestyle Interventions in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To perform a network meta-analysis to determine the effectiveness of lifestyle interventions in exercise tolerance and quality of life (QoL) in people with HFpEF. METHODS: Ten databases were searched for randomized controlled trials that evaluated a diet and/or exercise intervention in people with heart failure with preserved ejection fraction until May 2022. The co-primary outcomes were peak oxygen uptake (V̇O2peak) and Quality of Life as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). We synthesized data using network meta-analysis. RESULTS: We identified 13 trials, including a total of 869 participants, and we incorporated 6 different interventions. Improvements in V̇O2peak compared to controls were seen for all exercise interventions (2.88 [95% CI: 1.36; 4.39] mL/kg/min) for high-intensity interval training (HIIT); 2.37 [95% CI: 1.02; 3.71] mL/kg/min for low-intensity exercise (LIT) combined with a hypocaloric diet; 2.05 [95% CI: 0.81; 3.29] mL/kg/min for moderate-intensity continuous training (MICT); 1.94 [95% CI: 0.59; 3.29] mL/kg/min for LIT; 1.85 [95% CI: 0.27; 3.44] mL/kg/min for MICT combined with resistance training) but not a hypocaloric diet alone (1.26 [95%CI: -0.08; 2.61] mL/kg/min). Only HIIT (-14.45 [95%CI: -24.81; -4.10] points) and LIT (95% CI: -11.05 [-20.55; -1.54] mL/kg/min) significantly improved MLHFQ scores. Network meta-analysis indicated that HIIT was the most effective intervention for improving both V̇O2peak (mean improvement 2.88 [95% CI: 1.36; 4.39] mL/kg/min, follow-up range, 4 weeks-3 years) and QoL (-14.45 [95% CI: -24.81; -4.10] points, follow-up range, 12-26 weeks) compared to usual care. CONCLUSIONS: This network meta-analysis indicates that HIIT is the most effective lifestyle intervention studied to improve exercise capacity and QoL, with mean improvements exceeding the minimum clinically meaningful thresholds. HIIT is likely to be an underused management strategy in HFpEF, but further studies are needed to confirm long-term improvements in symptoms and clinical outcomes.

Participant and workplace champion experiences of an intervention designed to reduce sitting time in desk-based workers: SMART work & life.

BACKGROUND: A cluster randomised controlled trial demonstrated the effectiveness of the SMART Work & Life (SWAL) behaviour change intervention, with and without a height-adjustable desk, for reducing sitting time in desk-based workers. Staff within organisations volunteered to be trained to facilitate delivery of the SWAL intervention and act as workplace champions. This paper presents the experiences of these champions on the training and intervention delivery, and from participants on their intervention participation. METHODS: Quantitative and qualitative feedback from workplace champions on their training session was collected. Participants provided quantitative feedback via questionnaires at 3 and 12 month follow-up on the intervention strategies (education, group catch ups, sitting less challenges, self-monitoring and prompts, and the height-adjustable desk [SWAL plus desk group only]). Interviews and focus groups were also conducted at 12 month follow-up with workplace champions and participants respectively to gather more detailed feedback. Transcripts were uploaded to NVivo and the constant comparative approach informed the analysis of the interviews and focus groups. RESULTS: Workplace champions rated the training highly with mean scores ranging from 5.3/6 to 5.7/6 for the eight parts. Most participants felt the education increased their awareness of the health consequences of high levels of sitting (SWAL: 90.7%; SWAL plus desk: 88.2%) and motivated them to change their sitting time (SWAL: 77.5%; SWAL plus desk: 85.77%). A high percentage of participants (70%) reported finding the group catch up session helpful and worthwhile. However, focus groups highlighted mixed responses to the group catch-up sessions, sitting less challenges and self-monitoring intervention components. Participants in the SWAL plus desk group felt that having a height-adjustable desk was key in changing their behaviour, with intrinsic as well as time based factors reported as key influences on the height-adjustable desk usage. In both intervention groups, participants reported a range of benefits from the intervention including more energy, less fatigue, an increase in focus, alertness, productivity and concentration as well as less musculoskeletal problems (SWAL plus desk group only). Work-related, interpersonal, personal attributes, physical office environment and physical barriers were identified as barriers when trying to sit less and move more. CONCLUSIONS: Workplace champion and participant feedback on the intervention was largely positive but it is clear that different behaviour change strategies worked for different people indicating that a 'one size fits all' approach may not be appropriate for this type of intervention. The SWAL intervention could be tested in a broader range of organisations following a few minor adaptations based on the champion and participant feedback. TRIAL REGISTRATION: ISCRCTN registry (ISRCTN11618007).

Implementation and engagement of the SMART Work & Life sitting reduction intervention: an exploratory analysis on intervention effectiveness.

BACKGROUND: To enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group. METHODS: The extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies. RESULTS: Workplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p < 0.001) fewer minutes/day respectively compared to the control group at 12 month follow up. These differences were larger than the complete case analysis. The differences in sitting time observed for the medium and low levels were similar to the complete case analysis. CONCLUSIONS: Most intervention strategies were delivered to some extent across the clusters although there was large variation. Superior effects for sitting reduction were seen for those intervention groups who implemented and engaged with the most intervention components and had the highest level of cluster implementation and engagement. TRIAL REGISTRATION: ISRCTN11618007. Registered on 24 January 2018. https://www.isrctn.com/ISRCTNISRCTN11618007 .

A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials.

INTRODUCTION: Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios. METHODS: A systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus. RESULTS: Of 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable. CONCLUSIONS: It is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies. PROSPERO REGISTRATION NUMBER: CRD42022370910.

Incorporation of patient and public involvement in statistical methodology research: development of an animation.

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. METHODS: This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. RESULTS: After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (< 3 min) to optimise the communication of the key messages clearly and effectively. CONCLUSIONS: The resulting animation provides a starting point for members of the public to learn about PPIE in statistical methodology research and for methodologists who wish to conduct PPIE. We recommend further work to explore ways in which members of the public can be more meaningfully involved in methodology research.

Patient and public involvement and engagement (PPIE) is when members of the public are directly involved in carrying out research projects. This is important because we as researchers want to make sure we are focusing on what matters most to patients, so that the research has as large an impact as possible. PPIE has typically been used in more applied research projects, such as clinical trials, but is equally as important in statistical methodology research, where we focus on making sure the statistical tools that we use in the applied projects are as good as possible. The aim of this project was to create a short animation that helps to explain the importance of PPIE in statistical methodology research projects. Researchers sometimes incorrectly assume that PPIE is less important in these projects as this type of research has a less obvious benefit to patients. The animation helps to further explain these concepts. It describes what statistical methodology research is and why involving members of the public is still important. This paper explains the process of developing the animation, including receiving feedback from members of the public to make sure the animation is accessible to as many people as possible. The result is a short, 3-min animation that is free to view on the NIHR website. This can be used by other researchers to help them when recruiting members of the public to their research projects.

Association between ethnicity and migration status with the prevalence of single and multiple long-term conditions in UK healthcare workers.

BACKGROUND: Healthcare workers' (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status. METHODS: We used baseline data from the UK-REACH cohort study collected December 2020-March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK. RESULTS: Of 12,100 included HCWs, with a median age of 45 years (IQR: 34-54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66-0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30-3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05-2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55-0.83; Asian overseas-born aOR 0.75, 95%CI 0.62-0.90; Black overseas-born aOR 0.52, 95%CI 0.36-0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94-1.37). CONCLUSIONS: Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs.

Incorporation of patient and public involvement in statistical methodology research: a survey assessing current practices and attitudes of researchers.

BACKGROUND: Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area. METHODS: A descriptive cross-sectional research study was conducted using an online questionnaire, which asked statistical methodologists about themselves and their experience conducting PPI, either to inform a grant application or during a funded statistical methodology project. The survey included both closed-text responses, which were reported using summary statistics, and open-ended questions for which common themes were identified. RESULTS: 119 complete responses were recorded. Individuals who completed the survey displayed an even range of ages, career lengths and positions, with the majority working in academia. 40.3% of participants reported undertaking PPI to inform a grant application and the majority reported that the inclusion of PPI was received positively by the funder. Only 21.0% of participants reported undertaking PPI during a methodological project. 31.0% of individuals thought that PPI was "very" or "extremely" relevant to statistical methodology research, with 45.5% responding "somewhat" and 24.4% answering "not at all" or "not very". Arguments for including PPI were that it can provide the motivation for research and shape the research question. Negative opinions included that it is too technical for the public to understand, so they cannot have a meaningful impact. CONCLUSIONS: This survey found that the views of statistical methodologists on the inclusion of PPI in their research are varied, with some individuals having particularly strong opinions, both positive and negative. Whilst this is clearly a divisive topic, one commonly identified theme was that many researchers are willing to try and incorporate meaningful PPI into their research but would feel more confident if they had access to resources such as specialised training, guidelines, and case studies.

Patient and public involvement (or PPI) means researchers working in partnership with patients and the public in any part of research. It can include helping decide what the research question is, how to pass on results to the public, and telling researchers what areas are most important to patients and the public. Statistical methods are the tools we use to analyse data. Statistical methodology research involves making sure these tools use our healthcare data in the best way. PPI is essential in health research and is becoming more common in statistical methodology research. But it can be hard to know how to include patients and the public in statistical methodology research. It may seem complex and not directly related to patients. This paper describes the results from a survey we did about the experiences of researchers who have carried out PPI for statistical methodology research. We asked them what they think about it, and how it affects their research. We also asked if they feel confident including PPI in their research, and whether they are given enough help. Researchers had different views about PPI for statistical methodology research. Some people thought PPI was very important in their research, but others weren't sure. Many people said that they would like more help such as training and guidelines to help them do better PPI in the future.

Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study.

BACKGROUND: The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors - age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. METHODS: Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. RESULTS: The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. CONCLUSIONS: The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

A multicomponent intervention to reduce daily sitting time in office workers: the SMART Work & Life three-arm cluster RCT.

Background: Office workers spend 70-85% of their time at work sitting. High levels of sitting have been linked to poor physiological and psychological health. Evidence shows the need for fully powered randomised controlled trials, with long-term follow-up, to test the effectiveness of interventions to reduce sitting time. Objective: Our objective was to test the clinical effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable workstation, compared with usual practice at 12-month follow-up. Design: A three-arm cluster randomised controlled trial. Setting: Councils in England. Participants: Office workers. Intervention: SMART Work & Life is a multicomponent intervention that includes behaviour change strategies, delivered by workplace champions. Clusters were randomised to (1) the SMART Work & Life intervention, (2) the SMART Work & Life intervention with a height-adjustable workstation (i.e. SMART Work & Life plus desk) or (3) a control group (i.e. usual practice). Outcome measures were assessed at baseline and at 3 and 12 months. Main outcome measures: The primary outcome was device-assessed daily sitting time compared with usual practice at 12 months. Secondary outcomes included sitting, standing, stepping time, physical activity, adiposity, blood pressure, biochemical measures, musculoskeletal issues, psychosocial variables, work-related health, diet and sleep. Cost-effectiveness and process evaluation data were collected. Results: A total of 78 clusters (756 participants) were randomised [control, 26 clusters (n = 267); SMART Work & Life only, 27 clusters (n = 249); SMART Work & Life plus desk, 25 clusters (n = 240)]. At 12 months, significant differences between groups were found in daily sitting time, with participants in the SMART Work & Life-only and SMART Work & Life plus desk arms sitting 22.2 minutes per day (97.5% confidence interval -38.8 to -5.7 minutes/day; p = 0.003) and 63.7 minutes per day (97.5% confidence interval -80.0 to -47.4 minutes/day; p < 0.001), respectively, less than the control group. Participants in the SMART Work & Life plus desk arm sat 41.7 minutes per day (95% confidence interval -56.3 to -27.0 minutes/day; p < 0.001) less than participants in the SMART Work & Life-only arm. Sitting time was largely replaced by standing time, and changes in daily behaviour were driven by changes during work hours on workdays. Behaviour changes observed at 12 months were similar to 3 months. At 12 months, small improvements were seen for stress, well-being and vigour in both intervention groups, and for pain in the lower extremity and social norms in the SMART Work & Life plus desk group. Results from the process evaluation supported these findings, with participants reporting feeling more energised, alert, focused and productive. The process evaluation also showed that participants viewed the intervention positively; however, the extent of engagement varied across clusters. The average cost of SMART Work & Life only and SMART Work & Life plus desk was £80.59 and £228.31 per participant, respectively. Within trial, SMART Work & Life only had an incremental cost-effectiveness ratio of £12,091 per quality-adjusted life-year, with SMART Work & Life plus desk being dominated. Over a lifetime, SMART Work & Life only and SMART Work & Life plus desk had incremental cost-effectiveness ratios of £4985 and £13,378 per quality-adjusted life-year, respectively. Limitations: The study was carried out in one sector, limiting generalisability. Conclusions: The SMART Work & Life intervention, provided with and without a height-adjustable workstation, was successful in changing sitting time. Future work: There is a need for longer-term follow-up, as well as follow-up within different organisations. Trial registration: Current Controlled Trials ISRCTN11618007.

Office workers spend a large proportion of their day sitting. High levels of sitting have been linked to diseases, such as type 2 diabetes, heart disease and some cancers. The SMART Work & Life intervention is designed to reduce office workers' sitting time inside and outside work. The SMART Work & Life intervention involves organisational, environmental, group and individual strategies to encourage a reduction in sitting time and was designed to be delivered with and without a height-adjustable workstation (which allows the user to switch between sitting and standing while working). To test whether or not the SMART Work & Life intervention worked, we recruited 756 office workers from councils in Leicester/Leicestershire, Greater Manchester and Liverpool, UK. Participants were from 78 office groups. One-third of the participants received the intervention, one-third received the intervention with a height-adjustable workstation and one-third were a control group (and carried on as usual). Workplace champions in each office group were given training and resources to deliver the intervention. Data were collected at the start of the study, with follow-up measurements at 3 and 12 months. We measured sitting time using a small device worn on the thigh and collected data on weight, body fat, blood pressure, blood sugar and cholesterol levels. We asked participants about their health and work and spoke to participants to find out what they thought of the intervention. Our results showed that participants who received the intervention without workstation sat for 22 minutes less per day, and participants who received the intervention with workstation sat for 64 minutes less per day, than participants in the control group. Levels of stress, well-being, vigour (i.e. personal and emotional energy and cognitive liveliness) and pain in the lower extremity appeared to improve in the intervention groups. Participants viewed the intervention positively and reported several benefits, such as feeling more energised, alert, focused and productive; however, the extent to which participants engaged with the intervention varied across groups.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Implementation of a diabetes prevention programme in a multi-ethnic community in primary care in England: An evaluation using constructs from the RE-AIM Framework.

AIMS: To implement a diabetes prevention programme in primary care METHODS: The programme was implemented for 12 months in two neighbouring towns, served by eight general practices. Practices requested a referral pathway involving an external administrator running electronic searches and sending postal invitations. If interested, people called and booked a place on the programme. Practices were also provided with resources to refer people directly. Six Educators were trained to deliver the programme. The RE-AIM constructs "Adoption", "Reach" and "Uptake" were assessed. RESULTS: All practices engaged in the searches and postal invitations. Overall, 3.9 % of those aged ≥ 25 years had an HbA1c level indicative of non-diabetic hyperglycaemia (NDH) and were invited. Overall uptake (attended as percentage of invited) was 16 % (practice range 10.5-26.6 %) and was highest in two practices where the invitation was followed by a telephone call. Four people were referred directly by their practice. Groups at risk of being excluded were the Bengali population and those unable to attend because of issues such as health, mobility and frailty. CONCLUSIONS: Comprehensive electronic searches meant everyone previously diagnosed with NDH was invited to attend. Follow-up telephone call improved uptake and providing practices with resources to make these calls themselves would likely increase uptake further.

Hierarchical network meta-analysis models for synthesis of evidence from randomised and non-randomised studies.

BACKGROUND: With the increased interest in the inclusion of non-randomised data in network meta-analyses (NMAs) of randomised controlled trials (RCTs), analysts need to consider the implications of the differences in study designs as such data can be prone to increased bias due to the lack of randomisation and unmeasured confounding. This study aims to explore and extend a number of NMA models that account for the differences in the study designs, assessing their impact on the effect estimates and uncertainty. METHODS: Bayesian random-effects meta-analytic models, including naïve pooling and hierarchical models differentiating between the study designs, were extended to allow for the treatment class effect and accounting for bias, with further extensions allowing for bias terms to vary depending on the treatment class. Models were applied to an illustrative example in type 2 diabetes; using data from a systematic review of RCTs and non-randomised studies of two classes of glucose-lowering medications: sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. RESULTS: Across all methods, the estimated mean differences in glycated haemoglobin after 24 and 52 weeks remained similar with the inclusion of observational data. The uncertainty around these estimates reduced when conducting naïve pooling, compared to NMA of RCT data alone, and remained similar when applying hierarchical model allowing for class effect. However, the uncertainty around these effect estimates increased when fitting hierarchical models allowing for the differences in study design. The impact on uncertainty varied between treatments when applying the bias adjustment models. Hierarchical models and bias adjustment models all provided a better fit in comparison to the naïve-pooling method. CONCLUSIONS: Hierarchical and bias adjustment NMA models accounting for study design may be more appropriate when conducting a NMA of RCTs and observational studies. The degree of uncertainty around the effectiveness estimates varied depending on the method but use of hierarchical models accounting for the study design resulted in increased uncertainty. Inclusion of non-randomised data may, however, result in inferences that are more generalisable and the models accounting for the differences in the study design allow for more detailed and appropriate modelling of complex data, preventing overly optimistic conclusions.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis.

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]). Interpretation: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness. Funding: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Structured group education programme and accompanying mHealth intervention to promote physical activity in women with a history of gestational diabetes: A randomised controlled trial.

AIMS: Assess effectiveness of a hybrid intervention targeting physical activity in women with prior gestational diabetes. METHODS: Randomised controlled trial with parallel arms. 293 women (35.1 ± 5.1 years; 40% ethnic minority) recruited from two hospitals and randomised to routine care or hybrid lifestyle intervention comprising two group sessions and access to a mobile web app. Primary outcome was a change in objectively measured physical activity at 12 months. Secondary outcomes included self-efficacy for exercise, quality of life and anxiety and depression. Linear regression compared outcome measures between groups. RESULTS: 83% of intervention participants attended at least one group session, of who 66% registered to use the app. There was a non-significant increase in physical activity at 12 months (between-group difference of 0.95 mg [95% CI: -0.46 to 2.37]), equivalent to approximately 500 steps per day. Intervention participants reported higher self-efficacy for exercise (0.54, 95% CI: 0.05 to 1.102; p = 0.029), lower anxiety (-0.91, 95% CI: -1.74 to -0.09; p = 0.031), and higher quality of life (0.05, 95% CI: 0.004 to 0.09; p = 0.032), compared to controls. CONCLUSIONS: The intervention improved confidence in exercise and quality of life. Further research is needed to improve participant engagement with physical activity interventions in multi-ethnic populations with a history of gestational diabetes.

Ethnic inequalities in COVID-19 infection, hospitalisation, intensive care admission, and death: a global systematic review and meta-analysis of over 200 million study participants.

Background: COVID-19 has exacerbated existing ethnic inequalities in health. Little is known about whether inequalities in severe disease and deaths, observed globally among minoritised ethnic groups, relates to greater infection risk, poorer prognosis, or both. We analysed global data on COVID-19 clinical outcomes examining inequalities between people from minoritised ethnic groups compared to the ethnic majority group. Methods: Databases (MEDLINE, EMBASE, EMCARE, CINAHL, Cochrane Library) were searched from 1st December 2019 to 3rd October 2022, for studies reporting original clinical data for COVID-19 outcomes disaggregated by ethnicity: infection, hospitalisation, intensive care unit (ICU) admission, and mortality. We assessed inequalities in incidence and prognosis using random-effects meta-analyses, with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) use to assess certainty of findings. Meta-regressions explored the impact of region and time-frame (vaccine roll-out) on heterogeneity. PROSPERO: CRD42021284981. Findings: 77 studies comprising over 200,000,000 participants were included. Compared with White majority populations, we observed an increased risk of testing positive for infection for people from Black (adjusted Risk Ratio [aRR]:1.78, 95% CI:1.59-1.99, I2 = 99.1), South Asian (aRR:3.00, 95% CI:1.59-5.66, I2 = 99.1), Mixed (aRR:1.64, 95% CI:1.02-1.67, I2 = 93.2) and Other ethnic groups (aRR:1.36, 95% CI:1.01-1.82, I2 = 85.6). Black, Hispanic, and South Asian people were more likely to be seropositive. Among population-based studies, Black and Hispanic ethnic groups and Indigenous peoples had an increased risk of hospitalisation; Black, Hispanic, South Asian, East Asian and Mixed ethnic groups and Indigenous peoples had an increased risk of ICU admission. Mortality risk was increased for Hispanic, Mixed, and Indigenous groups. Smaller differences were seen for prognosis following infection. Following hospitalisation, South Asian, East Asian, Black and Mixed ethnic groups had an increased risk of ICU admission, and mortality risk was greater in Mixed ethnic groups. Certainty of evidence ranged from very low to moderate. Interpretation: Our study suggests that systematic ethnic inequalities in COVID-19 health outcomes exist, with large differences in exposure risk and some differences in prognosis following hospitalisation. Response and recovery interventions must focus on tackling drivers of ethnic inequalities which increase exposure risk and vulnerabilities to severe disease, including structural racism and racial discrimination. Funding: ESRC:ES/W000849/1.