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To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D.At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

Background Hypertension is common in individuals with chronic kidney disease and both conditions are associated with adverse outcomes including cardiovascular morbidity. Therefore, it is clinically important to identify methods of risk prediction in individuals with chronic kidney disease. Blood pressure variability has recently emerged as a predictor of cardiovascular events and mortality in the general population, with growing evidence indicating that it may play a similar role in individuals with chronic kidney disease. However, there have been no large studies assessing blood pressure variability in individuals with chronic kidney disease in primary care, where the majority of these patients are managed. Method Using a retrospective observational study design, we analyzed routinely collected blood pressure readings from 16 999 individuals in The Leicester and County Chronic Kidney Disease cohort. Standard deviation, coefficient of variation and average real variability of SBP were used to calculate blood pressure variability. Results During a median follow-up of 5.0 (IQR 3.3--5.0) years, 2053 (12.1%) patients had cardiovascular events, death occurred in 5021 (29.6%) individuals and 156 (0.9%) individuals had endstage kidney disease events. In adjusted models, standard deviation and coefficient of variation were associated with cardiovascular events, all-cause mortality and endstage kidney disease. Average real variability was associated with all-cause mortality and cardiovascular events, but not endstage kidney disease. Conclusion Blood pressure variability may be an accessible, routinely collected, noninvasive measure for stratifying the risk of adverse events in individuals with chronic kidney disease in a primary care setting.

Objective A significant proportion of vascular surgery patients may have undiagnosed cognitive impairment; however, its true prevalence and impact on outcomes are unknown. The aim of this review was to estimate the prevalence of cognitive impairment among individuals with clinically significant vascular surgical pathology and investigate its associations with post-operative outcomes in those undergoing vascular surgery. Methods MEDLINE, EMBASE, EMCare, CINAHL, PsycINFO, and Scopus were searched for relevant studies. Included studies assessed cognitive function among individuals with either symptomatic vascular surgical pathology, or disease above threshold for intervention, using a validated cognitive assessment tool. The primary outcome measure was prevalence of cognitive impairment. Secondary outcomes included incidence of post-operative delirium (POD). Two reviewers independently extracted relevant study data and assessed risk of bias (ROBINS-E or RoB 2 tool). Prevalence (%) of cognitive impairment was calculated for individual studies and presented with 95% confidence intervals (CI). Prevalence data from comparable studies were pooled using the Mantel-Haenszel method (random effects model) for separate vascular disease types. Certainty of effect estimates was assessed using the GRADE criteria. Results Twenty-four studies (2 564 participants) were included in the systematic review, and nine studies (1 310 participants) were included in the meta-analyses. The prevalence of cognitive impairment was 61% (95% CI 48 – 74; 391 participants; low certainty) in studies including multiple vascular surgical pathologies, 38% (95% CI 32 – 44; 278 participants; very low certainty) in carotid artery disease, and 19% (95% CI 10 – 33; 641 participants; low certainty) in those with intermittent claudication. Lower cognitive assessment scores were associated with POD (five studies; 841 participants), but data were not suitable for pooling. Conclusion Screening elective vascular surgery patients for cognitive impairment may be appropriate given its high prevalence, and the association of worse cognition with POD, among individuals with clinically significant vascular surgical pathology.

Objective Vascular limb salvage services are recommended by the Global Vascular Guidelines to help improve outcomes for patients with chronic limb-threatening ischaemia (CLTI), although their description within the literature is limited. This study reports the 12 month outcomes for an outpatient based vascular limb salvage (VaLS) clinic. Methods An analysis of a prospectively maintained database, involving all consecutive patients diagnosed with CLTI within the VaLS clinic from February 2018–February 2019, was undertaken. Data were compared with two comparator cohorts, identified from coding data: 1) patients managed prior to the clinic, between May 2017 and February 2018 (Pre-Clinic [PC]); and 2) patients managed outside of clinic, between February 2018 and February 2019 (Alternative Pathways [AP]). Freedom from major amputation at 12 months was the primary outcome. Kaplan–Meier plots and adjusted Cox’s proportional hazard models (aHR) were used to compare outcomes. Results Five hundred and sixty-six patients (VaLS 158, AP 173, PC 235) were included (median age 74 years). Patients managed within the VaLS cohort were statistically significantly more likely to be free from major amputation (90.5%) compared with both the AP (82.1%, aHR 0.52, 95% confidence interval [CI] 0.28 – 0.98, p = .041) and the PC (80.0%; aHR 0.50, 95% CI 0.28 – 0.91, p = .022) cohorts at 12 months, after adjustment for age, disease severity, and presence of diabetes. Conclusion This study supports the recommendations of the Global Vascular Guidelines that vascular limb salvage clinics may improve the rate of major amputation. Furthermore, the study provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting. Further evaluation is required to assess longer term outcomes.

Background South Asian (SA) individuals are more likely to develop end-stage renal disease (ESRD), but how chronic kidney disease (CKD) differs in relation to demographics, comorbidities and outcomes has not been studied. We aimed to study differences in SA individuals with CKD compared with White individuals. Methods This was an observational CKD cohort comparing SA with White individuals. Inclusion criteria were ≥18 years of age and two or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRs 3 months apart. Individuals with ESRD at baseline were excluded. Baseline characteristics, including eGFR formulae [CKD-EPI and CKD-EPI-Pakistan (CKD-EPI-PK)], were compared. Analysis using competing risk regression for cardiovascular (CV) and ESRD events and Cox proportional hazard model for mortality was performed. Results From an adult population of 277 248 individuals, 17 248 individuals had CKD, of whom 1990 (11.5%) were of SA ethnicity. Age-adjusted prevalence of CKD was similar between ethnicities. SA individuals were more likely to be male, younger and socioeconomically deprived, and to have diabetes mellitus, CV disease and advanced CKD. Mean CKD-EPI-PK eGFR was 6.5 mL/min/1.73 m2 lower (41.1 versus 47.6, 95% confidence interval for difference 6.47–6.56) than for CKD-EPI. During 5 years of follow-up, 5109 (29.6%) individuals died, 2072 (12.0%) had a CV and 156 (0.90%) an ESRD event. Risk for SA individuals was higher for ESRD, similar to CV events and lower for mortality. Each 1 mL/min/1.73 m2 decrease in CKD-EPI-PK was associated with a 13.1% increased ESRD risk (adjusted subdistribution hazard ratio 0.869, 95% confidence interval 0.841–0.898). Conclusions SA individuals with CKD were younger and had more advanced disease than White individuals. Risk of ESRD was higher and CKD-EPI-PK was associated with ESRD risk in SA individuals. Specific CKD interventions, including the use of CKD-EPI-PK, should be considered in SA populations.

To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity.In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/mThe mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions.In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy.NCT02798744, www.gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

BackgroundFewer trials are conducted in nephrology than any other specialty, often failing to recruit to target, resulting in unclear evidence affecting translation to clinical practice. This mixed-methods study aims to provide guidance for designing and reporting future randomised controlled trials (RCTs) in the haemodialysis population.MethodA scoping review was conducted. Five databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched for RCTs published between 2013 and 2019 involving prevalent adult haemodialysis patients. Reporting of sample size, recruitment, retention and statistical significance of primary outcome were assessed. Face-to-face semistructured interviews were conducted with individuals from a single centre during dialysis sessions. Interviews were analysed thematically.ResultsOf 786 RCTs identified, 636 (80.9%) were parallel-group, 139 (17.7%) were crossover and 11 (1.4%) were cluster (including one stepped-wedge) design. Sample size justification was reported in 73.1%, 53.8% and 45.5% of parallel-group, crossover and cluster trials, respectively.Target recruitment was achieved by 45.5% of cluster, 53.8% of crossover and 57.7% of parallel-group trials with patient retention at 75.6%, 83.1% and 87.8%, respectively. Primary outcome reached statistical significance in 81.8% of cluster trials, 69.2% of parallel-group and 38.5% of crossover trials.Themes identified from individual interviews: perceptions of the convenience of trial participation; group allocation; perceptions of the benefits and adverse effects of taking part in clinical trials.ConclusionThe recruitment and reporting of RCTs involving people on haemodialysis could be improved. Involvement of all stakeholders and especially participants in the trial design process may address issues around participant burden and ultimately improve the evidence base for clinical practice.

This systematic review and meta-analysis determined the impact of exercise training on adipose tissue insulin sensitivity in adults. Its scope extended to studies measuring whole-body and localized subcutaneous adipose tissue insulin sensitivity using validated techniques. Consensus from four studies demonstrates that exercise training improved whole-body adipose tissue insulin sensitivity when measured via stable-isotope lipid tracers (rate of appearance suppression in response to hyperinsulinemia). Meta-analysis of 20 studies (26 intervention arms) employing the adipose tissue insulin resistance index (ADIPO-IR) supported these findings (-10.63 [-14.12 to -7.15] pmol·L

Aim Type 2 diabetes is a growing global challenge. Evidence exists demonstrating the use of primary care (non-hospital based) dental practices to identify, through risk assessments, those who may be at increased risk of type 2 diabetes or who may already unknowingly have the condition. This review aimed to synthesize evidence associated with the use of primary care dental services for the identification of undiagnosed non-diabetic hyperglycaemia or type 2 diabetes in adults, with particular focus on the pick-up rate of new cases. Method Electronic databases were searched for studies reporting the identification of non-diabetic hyperglycaemia/type 2 diabetes in primary care dental settings. Returned articles were screened and two independent reviewers completed the data-extraction process. A descriptive synthesis of the included articles was undertaken due to the heterogeneity of the literature returned. Results Nine studies were identified, the majority of which utilized a two-stage risk-assessment process with risk score followed by a point-of-care capillary blood test. The main barriers cited were cost, lack of adequate insurance cover and people having previously been tested elsewhere. The pick-up rate of new cases of type 2 diabetes and non-diabetic hyperglycaemia varied greatly between studies, ranging from 1.7% to 24% for type 2 diabetes and from 23% to 45% for non-diabetic hyperglycaemia, where reported. Conclusion This review demonstrates that although it appears there may be benefit in using the dental workforce to identify undiagnosed cases of non-diabetic hyperglycaemia and type 2 diabetes, further high-quality research in the field is required assessing both the clinical and cost effectiveness of such practice. (Prospero Registration ID: PROSPERO 2018 CRD42018098750).

To investigate the actions of lithium, valproate, lamotrigine and quetiapine on bioenergetic pathways in cultured NT2-N neuronal-like cells and C8-B4 microglial cells.NT2-N and C8-B4 cells were cultured and treated with lithium (2.5 mM), valproate (0.5 mM), quetiapine (0.05 mM) or lamotrigine (0.05 mM) for 24 hours. Gene expression and the mitochondrial bioenergetic profile were measured in both cell lines.In NT2-N cells, valproate increased oxidative phosphorylation (OXPHOS) gene expression, mitochondrial uncoupling and maximal respiratory capacity, while quetiapine decreased OXPHOS gene expression and respiration linked to ATP turnover, as well as decreasing the expression of genes in the citric acid cycle. Lamotrigine decreased OXPHOS gene expression but had no effect on respiration, while lithium reduced the expression of genes in the citric acid cycle. In C8-B4 cells, valproate and lithium increased OXPHOS gene expression, and valproate increased basal respiratory rate and maximal and spare respiratory capacities. In contrast, quetiapine significantly reduced basal respiratory rate and maximal and spare respiratory capacities.Overall our data suggest that some drugs used to treat neuropsychiatric and affective disorders have actions on a range of cellular bioenergetic processes, which could impact their effects in patients.

Purpose of Review Type 2 diabetes (T2DM) presents a growing global health and economic burden. Dental settings have been employed to identify individuals who may be at high risk of diabetes, who exhibit non-diabetic hyperglycaemia (NDH – also termed “prediabetes”) and who already unknowingly have the condition, through the use of targeted risk-assessments. This review aims to synthesize the existing literature supporting dental teams’ identification of individuals at an increased risk of or suffering from undiagnosed NDH or T2DM in dental specialist care settings. Recent Findings Electronic databases were searched for studies reporting the identification of NDH and or T2DM, in specialist care dental settings. Screening of returned articles and data extraction were completed by two independent reviewers (RJ, ZY). A descriptive synthesis of the included articles was undertaken. Due to heterogeneity of the literature, a meta-analysis could not be performed. The search yielded 52 eligible studies, of which 12 focused primarily on stakeholder opinions. Opinions of patients, dentists, dental hygienists, dental students and physicians on case identification of T2DM by oral health professionals were generally positive. The main barriers cited were time, cost, inadequate training and low follow-up of participants by primary care physicians. The risk assessment processes varied, with most studies using a combination of methods consisting of a questionnaire followed by a chairside blood sample. Methods utilizing questionnaires, gingival crevicular blood (GCB), fingerstick blood (FSB) and urine samples have all been evaluated. Summary This review demonstrates that there may be benefit in engaging the dental workforce to identify cases of NDH and undiagnosed T2DM and that such a care pathway has the support of multiple stakeholders. Further high-quality research is required to assess both the clinical and cost-effectiveness of such practice in order to optimize protocols and patient care pathways. Studies should include a comparison of methods, health economic analyses and protocols to ensure those identified as high-risk go on to receive appropriate follow-up care.

Background:The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs.Methods:The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at pResults:We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( pConclusions:We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.

ObjectivesTo investigate how ethnicity and other sociodemographic, work, and physical health factors are related to mental health in UK healthcare and ancillary workers (HCWs), and how structural inequities in these factors may contribute to differences in mental health by ethnicity.DesignCross-sectional analysis of baseline data from the UK-REACH national cohort studySettingHCWs across UK healthcare settings.Participants11,695 HCWs working between December 2020-March 2021.Main outcome measuresAnxiety or depression symptoms (4-item Patient Health Questionnaire, cut-off >3), and Post-Traumatic Stress Disorder (PTSD) symptoms (3-item civilian PTSD Checklist, cut-off >5).ResultsAsian, Black, Mixed/multiple and Other ethnic groups had greater odds of PTSD than the White ethnic group. Differences in anxiety/depression were less pronounced. Younger, female HCWs, and those who were not doctors had increased odds of symptoms of both PTSD and anxiety/depression. Ethnic minority HCWs were more likely to experience the following work factors that were also associated with mental ill-health: workplace discrimination, feeling insecure in raising workplace concerns, seeing more patients with COVID-19, reporting lack of access to personal protective equipment (PPE), and working longer hours and night shifts. Ethnic minority HCWs were also more likely to live in a deprived area and have experienced bereavement due to COVID-19. After adjusting for sociodemographic and work factors, ethnic differences in PTSD were less pronounced and ethnic minority HCWs had lower odds of anxiety/depression compared to White HCWs.ConclusionsEthnic minority HCWs were more likely to experience PTSD and disproportionately experienced work and sociodemographic factors associated with PTSD, anxiety and depression. These findings could help inform future work to develop workplace strategies to safeguard HCWs’ mental health. This will only be possible with adequate investment in staff recruitment and retention, alongside concerted efforts to address inequities due to structural discrimination.Summary boxWhat is already known on this topicThe pandemic is placing healthcare workers under immense pressure, and there is currently a mental health crisis amongst NHS staffEthnic inequities in health outcomes are driven by structural discrimination, which occurs inside and outside the workplaceInvestigating ethnic inequities in the mental health of healthcare workers requires large diverse studies, of which few existWhat this study addsIn UK-REACH (N=11,695), ethnic minority staff had higher odds of Post-Traumatic Stress Disorder symptoms; we report many other factors associated with mental-ill health, including those experienced disproportionately by ethnic minority staff, such as workplace discrimination, contact with more patients with COVID-19, and bereavement due to COVID-19These findings underline the moral and practical need to care for staff mental health and wellbeing, which includes tackling structural inequities in the workplace; improving staff mental health may also reduce workforce understaffing due to absence and attrition

Background Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. Methods and findings We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. Conclusions We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. Trial registration The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).

Key Features of the UK-REACH Cohort (Profile in a nutshell)The UK-REACH Cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared to their white ethnic counterparts in the United Kingdom (UK). Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data has been collected.A total of 17891 HCWs aged 16-89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service (NHS) hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study.Data available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition, and opinions on COVID-19 vaccines, with baseline (n=15 119), 6 (n=5632) and 12-month follow-up data captured.Request data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing.

Background and ObjectivesRisk factors for cardiovascular disease in chronic kidney disease differ to the general population due to the increased role of inflammation, calcification and arteriosclerosis. Over 350 cardiovascular risk models (“models”) exist in the general population but most have not undergone testing (“external validation”) in other populations, such as cohorts with chronic kidney disease. We aimed to update a previous systematic review of models in chronic kidney disease and then perform external validation of these and general population models in a chronic kidney disease cohort.Design, Setting, Participants and MeasurementsWe searched Medline up to 26th August 2020 for models in chronic kidney disease. We performed external validation of models using a primary care chronic kidney disease cohort of 17,248 individuals with 2,072 (12.0%) cardiovascular events, 5,108 (29.6%) deaths and a median follow-up of 5.0 years. Model discrimination and calibration was assessed and where appropriate models were re-calibrated. Multiple imputation was used to account for missing data.ResultsSeven chronic kidney disease specific models were identified. These models and three general population models underwent external validation. All models had worse discrimination of events than in their original cohorts, particularly in the chronic kidney disease specific models. General population models were miscalibrated and overpredicted risk. The major contributor to this was the high competing risk of death from non-cardiovascular causes.ConclusionsExisting chronic kidney disease cardiovascular risk models performed poorly in external validation. General population cardiovascular disease risk models should be interpreted with caution in individuals with chronic kidney disease as they may overestimate risk due to the competing risk of death. Further development of models to include simultaneous risk prediction for cardiovascular and non-cardiovascular disease risk is required.

BackgroundSeveral countries now have mandatory SARS-CoV-2/COVID-19 vaccination for healthcare workers (HCWs) or the general population. HCWs’ views on this are largely unknown.MethodsWe administered an online questionnaire to 17891 United Kingdom (UK) HCWs in Spring 2021 as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question “What should society do if people don’t get vaccinated against COVID-19?” using content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not and used logistic regression to calculate its demographic predictors, and occupational, health and attitudinal predictors adjusted for demographics.FindingsOf 5633 questionnaire respondents, 3235 answered the freetext question; 18% (n=578) of those favoured mandatory vaccination but the most frequent suggestion was education (32%, n=1047). Older HCWs, HCWs vaccinated against influenza (OR 1.48; 95%CI 1.10 – 1.99, vs none) and with more positive vaccination attitudes generally (OR 1.10; 95%CI 1.06 – 1.14) were more likely to favour mandatory vaccination (OR 1.26; 95%CI 1.17 – 1.37, per decade increase), whereas female HCWs (OR= 0.80, 95%CI 0.65 – 0.99, vs male), Black HCWs (OR= 0.48, 95%CI 0.26 – 0.87, vs White), those hesitant about COVID-19 vaccination (OR= 0.56; 95%CI 0.43 – 0.71, vs not hesitant), in an Allied Health Profession (OR 0.67; 95%CI 0.51 – 0.88, vs Medical), or who trusted their organisation (OR 0.78; 95%CI 0.63 – 0.96) were less likely to.InterpretationOnly one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating and supporting HCWs who are hesitant about vaccination may be more acceptable, effective and equitable.FundingMRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care via the National Institute for Health Research.

Aims: Major lower extremity amputations (MLEAs) are understood to be well recorded in secondary care in England in the Hospital Episode Statistics (HES) database. It is unclear how well MLEAs are recorded in primary care databases. Background: This study compared MLEA event case ascertainment in Clinical Practice Research Datalink (CPRD) to that in HES. Methods: MLEA events were ascertained in CPRD and in HES linkage between 1 January 2010 and 31 December 2019. The number of MLEA events and the number of patients with at least one MLEA in each database were recorded and compared. Individual events were matched between the databases using varying date-matching windows. Reasons for differences in case ascertainment were explored. Findings: In total 23 262 patients had at least one MLEA record, 8716 (37.5%) had an MLEA record in HES only, 5393 (23.2%) in CPRD only and 9153 (39.4%) in both. Out of a total of 75 221 events, 13 071 (62.4%) were recorded in HES only and 44 151 (81.3%) in CPRD only. 7874 (37.6%) of HES events were recorded in CPRD and 10 125 (18.6%) of CPRD events were recorded in HES when using the maximum date matching window of 28 days plus the time between admission and procedure. The main reasons for differences in case ascertainment included, re-recordings and miscoding in CPRD. Compared to HES, MLEAs are poorly recorded in CPRD predominantly due to re-recordings of events and miscoding procedures. CPRD data cannot solely be relied upon to ascertain cases of MLEA; however, HES linkage to CPRD may be useful to obtain medical history of diagnoses, medication and diagnostic tests.

IntroductionHealthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.MethodsWe conducted a cross-sectional analysis using data from the United Kingdom Research study into Ethnicity And COVID-19 Outcomes in Healthcare workers (UK-REACH) cohort study. We used logistic regression to examine associations of demographic, household and occupational predictor variables with SARS-CoV-2 infection (defined by PCR, serology or suspected COVID-19) in a diverse group of HCWs.Results2,496 of the 10,772 HCWs (23.2%) who worked during the first UK national lockdown in March 2020 reported previous SARS-CoV-2 infection. In an adjusted model, demographic and household factors associated with increased odds of infection included younger age, living with other key workers and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.49, 95%CI 2.03–3.05 for ≥21 patients per week vs none), working in a nursing or midwifery role (1.35, 1.15– 1.58, compared to doctors), reporting a lack of access to personal protective equipment (1.27, 1.15 – 1.41) and working in an ambulance (1.95, 1.52–2.50) or hospital inpatient setting (1.54, 1.37 – 1.74). Those who worked in Intensive Care Units were less likely to have been infected (0.76, 0.63–0.90) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known predictors.ConclusionsWe identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection amongst UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.Trial registrationISRCTN 11811602

BackgroundVaccination is key to successful prevention of COVID-19 particularly nosocomial acquired infection in health care workers (HCWs). ‘Vaccine hesitancy’ is common in the population and in HCWs, and like COVID-19 itself, hesitancy is more frequent in ethnic minority groups. UK-REACH (United Kingdom Research study into Ethnicity and COVID-19 outcomes) is a large-scale study of COVID-19 in UK HCWs from diverse ethnic backgrounds, which includes measures of vaccine hesitancy. The present study explores predictors of vaccine hesitancy using a ‘phenomic approach’, considering several hundred questionnaire-based measures.MethodsUK-REACH includes a questionnaire study encompassing 12,431 HCWs who were recruited from December 2020 to March 2021 and completed a lengthy online questionnaire (785 raw items; 392 derived measures; 260 final measures). Ethnicity was classified using the Office for National Statistics’ five (ONS5) and eighteen (ONS18) categories. Missing data were handled by multiple imputation. Variable selection used theislassopackage inR, which provides standard errors so that results from imputations could be combined using Rubin’s rules. The data were modelled using path analysis, so that predictors, and predictors of predictors could be assessed. Significance testing used the Bayesian approach of Kass and Raftery, a ‘very strong’ Bayes Factor of 150, N=12,431, and a Bonferroni correction giving a criterion of p−8for the main regression, and p−10for variables in the path analysis.ResultsAt the first step of the phenomic analysis, six variables were direct predictors of greater vaccine hesitancy: Lower pro-vaccination attitudes; no flu vaccination in 2019-20; pregnancy; higher COVID-19 conspiracy beliefs; younger age; and lower optimism the roll-out of population vaccination. Overall 44 lower variables in total were direct or indirect predictors of hesitancy, with the remaining 215 variables in the phenomic analysis not independently predicting vaccine hesitancy. Key variables for predicting hesitancy were belief in conspiracy theories of COVID-19 infection, and a low belief in vaccines in general. Conspiracy beliefs had two main sets of influences:Higher Fatalism, which was influenced a) by high external and chance locus of control and higher need for closure, which in turn were associated with neuroticism, conscientiousness, extraversion and agreeableness; and b) by religion being important in everyday life, and being Muslim.receiving information via social media, not having higher education, and perceiving greater risks to self, the latter being influenced by higher concerns about spreading COVID, greater exposure to COVID-19, and financial concerns.There were indirect effects of ethnicity, mediated by religion. Religion was more important for Pakistani and African HCWs, and less important for White and Chinese groups. Lower age had a direct effect on hesitancy, and age and female sex also had several indirect effects on hesitancy.ConclusionsThe phenomic approach, coupled with a path analysis revealed a complex network of social, cognitive, and behavioural influences on SARS-Cov-2 vaccine hesitancy from 44 measures, 6 direct and 38 indirect, with the remaining 215 measures not having direct or indirect effects on hesitancy. It is likely that issues of trust underpin many associations with hesitancy. Understanding such a network of influences may help in tailoring interventions to address vaccine concerns and facilitate uptake in more hesistant groups.FundingUKMRI-MRC and NIHR

BackgroundTargeted self-management programmes may improve health and increase physical activity (PA) in people with multimorbidity.AimTo investigate the impact of a structured, theoretically driven, self-management group education programme on habitual PA levels in people with multimorbidity.Design and settingIndividually randomised controlled trial with 12-month follow-up, involving nine primary care practices in Leicestershire, UK.MethodIn total, 353 adults with multimorbidity (age 67.8 years [±9 years], 161 male sex) were randomised to intervention (n= 180) or control (n= 173) groups. Intervention participants were invited to attend four group-based self-management sessions, centred primarily on increasing PA, and received motivational text-message support. The primary outcome measure was change in overall volume (time and intensity) of daily PA at 12 months, as measured by the GENEActiv wrist-worn accelerometer device.ResultsAt baseline, the total sample achieved 22 min of moderate–vigorous intensity PA per day (mean/participant). At 12 months, in the complete-case analysis, a reduction in daily mean PA volume was seen in the intervention group relative to control (−0.80 milligravity [mg]; 95% confidence interval [CI] = −1.57 to −0.03;P= 0.04). Reductions were also seen in the intervention group in time spent in moderate–vigorous PA (−3.86 min per day; 95% CI= −6.70 to −1.03;P= 0.008) and time spent at an intensity equivalent to a slow walk (−4.66 min per day; 95% CI = −8.82 to −0.51;P= 0.028). However, the per-protocol analysis (excluding participants who did not attend at least one education session) found no between-group differences in overall daily PA at 12 months (−0.65 mg; 95% CI = −1.46 to 0.15;P= 0.11).ConclusionThe self-management programme elicited a slight reduction in PA levels in people with multimorbidity. Future research should identify and target subgroups of those with multimorbidity in greatest need of PA promotion in order to maximise potential capacity for benefit, and also focus on refining the intervention in order to increase efficacy in increasing PA.

ObjectiveEstimate the prevalence/incidence/number of major lower extremity amputations (MLEAs) in the UK; identify sources of routinely collected electronic health data used; assess time trends and regional variation; and identify reasons for variation in reported incidence/prevalence of MLEA.DesignSystematic review and narrative synthesis.Data sourcesMedline, Embase, EMcare, CINAHL, The Cochrane Library, AMED, Scopus and grey literature sources searched from 1 January 2009 to 1 August 2021.Eligibility criteria for selecting studiesReports that provided population-based statistics, used routinely collected electronic health data, gave a measure of MLEA in adults in the general population or those with diabetes in the UK or constituent countries were included.Data extraction and synthesisData extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Instruments were performed by two reviewers independently. Due to considerable differences in study populations and methodology, data pooling was not possible; data were tabulated and narratively synthesised, and study differences were discussed.ResultsTwenty-seven reports were included. Incidence proportion for the general population ranged from 8.2 to 51.1 per 100 000 and from 70 to 291 per 100 000 for the population with diabetes. Evidence for trends over time was mixed, but there was no evidence of increasing incidence. Reports consistently found regional variation in England with incidence higher in the north. No studies reported prevalence. Differences in database use, MLEA definition, calculation methods and multiple procedure inclusion which, together with identified inaccuracies, may account for the variation in incidence.ConclusionsUK incidence and trends in MLEA remain unclear; estimates vary widely due to differences in methodology and inaccuracies. Reasons for regional variation also remain unexplained and prevalence uninvestigated. International consensus on the definition of MLEA and medical code list is needed. Future research should recommend standards for the reporting of such outcomes and investigate further the potential to use primary care data in MLEA epidemiology.Systematic review registrationPROSPERO CRD42020165592.

ObjectivesTo determine the prevalence and predictors of self-reported access to appropriate personal protective equipment (aPPE) for healthcare workers (HCWs) in the United Kingdom (UK) during the first UK national COVID-19 lockdown (March 2020) and at the time of questionnaire response (December 2020 – February 2021).DesignTwo cross sectional analyses using data from a questionnaire-based cohort study.SettingNationwide questionnaire from 4th December 2020 to 28th February 2021.ParticipantsA representative sample of HCWs or ancillary workers in a UK healthcare setting aged 16 or over, registered with one of seven main UK healthcare regulatory bodies.Main outcome measureBinary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK (primary analysis) and at the time of questionnaire response (secondary analysis).Results10,508 HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 3702 (35.2%) of HCWs reported aPPE at all times in the primary analysis; 6806 (83.9%) reported aPPE at all times in the secondary analysis. After adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector, work region, working hours, night shift frequency and trust in employing organisation), older HCWs (per decade increase in age: aOR 1.2, 95% CI 1.16-1.26, pConclusionsWe found that only a third of HCWs in the UK reported aPPE at all times during the period of the first lockdown and that aPPE had improved later in the pandemic. We also identified key sociodemographic and occupational determinants of aPPE during the first UK lockdown, the majority of which have persisted since lockdown was eased. These findings have important public health implications for HCWs, particularly as cases of infection and long-COVID continue to rise in the UK.Trial registrationISRCTN 11811602What is already known on this topicAccess to personal protective equipment (PPE) is crucial to protect healthcare workers (HCWs) from infection. Limited data exist concerning the prevalence of, and factors relating to, PPE access for HCWs in the United Kingdom (UK) during the COVID-19 pandemic.What this study addsOnly a third of HCWs reported having access to appropriate PPE all of the time during the first UK national lockdown. Older HCWs, those working in Intensive Care Units and those who trusted their employing organisation to deal with concerns about unsafe clinical practice, were more likely to report access to adequate PPE. Those from Asian ethnic groups (compared to White ethnic groups) and those who saw a high number of COVID-19 were less likely to report access to adequate PPE. Our findings have important implications for the mental and physical health of HCWs working during the pandemic in the UK.

IntroductionThe COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).Methods and analysisA baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.Ethics and disseminationThe study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.Trial registration numberISRCTN11811602; Pre-results.

Physical inactivity and obesity are widely prevalent in Heavy Goods Vehicle (HGV) drivers. We analysed whether obesity classification influenced the effectiveness of a bespoke structured lifestyle intervention (‘SHIFT’) for HGV drivers. The SHIFT programme was evaluated within a cluster randomised controlled trial, across 25 transport depots in the UK. After baseline assessments, participants within intervention sites received a 6-month multi-component health behaviour change intervention. Intervention responses (verses control) were stratified by obesity status (BMI < 30 kg/m2, n = 131; BMI ≥ 30 kg/m2, n = 113) and compared using generalised estimating equations. At 6-months, favourable differences were found in daily steps (adjusted mean difference 1827 steps/day, p < 0.001) and sedentary time (adjusted mean difference −57 min/day, p < 0.001) in drivers with obesity undertaking the intervention, relative to controls with obesity. Similarly, in drivers with obesity, the intervention reduced body weight (adjusted mean difference −2.37 kg, p = 0.002) and led to other favourable anthropometric outcomes, verses controls with obesity. Intervention effects were absent for drivers without obesity, and for all drivers at 16–18-months follow-up. Obesity classification influenced HGV drivers’ behavioural responses to a multi-component health-behaviour change intervention. Therefore, the most at-risk commercial drivers appear receptive to a health promotion programme.

IntroductionCOVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.Methods and analysisThis study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.Ethics and disseminationEthical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).Trial registration numberISRCTN11811602.

Introduction Single-centre studies have shown a high prevalence of undiagnosed cognitive impairment in patients undergoing vascular surgery. The aim of this meta-analysis was to estimate the pooled prevalence of cognitive impairment in vascular surgery patients. Methods A systematic review and meta-analysis was performed of studies reporting cognitive impairment in vascular surgery patients (PROSPERO registration: CRD42019134684). Databases searched included: Medline, Embase, Emcare, CINAHL, PsychINFO and Scopus. Studies were excluded if they: did not use a validated cognitive assessment tool, included patients with asymptomatic or sub-threshold (for treatment) disease, or excluded patients with cognitive impairment. Quality of included studies was assessed using Newcastle-Ottawa scores (NOS), risk of bias was assessed using the ROBINS-E tool, and quality of evidence assessed using GRADE criteria. A pooled estimate of prevalence was calculated using the inverse-variance method separately for carotid artery disease (CAD), lower extremity arterial disease (LEAD), and studies including patients with multiple vascular surgery presentations. Data were pooled using random effects models and estimated prevalence presented with 95% confidence intervals (95%CI). Subgroup analyses were performed by cognitive assessment tool used. Authors of 24 studies meeting inclusion criteria that did not report numbers of cognitively impaired patients were contacted to enable inclusion: responses are awaited. Results After de-duplication of search results, 7,169 records were screened and 11 studies (911 patients) included in the meta-analysis. Nine studies were deemed high quality (NOS ≥7) however 8 studies had a serious risk of bias. Only one study explicitly stated provision for recruiting patients without capacity. Six different tools were used to assess cognitive function (MoCA, MMSE, ACE-R, HDS-R, Mini-Cog and a global cognitive score). Two studies found an association of cognitive impairment with post-op delirium whilst one did not, and a further study showed an association with increased length of stay. Pooled estimate of prevalence of cognitive impairment in CAD patients was 38% (95%CI 17%, 62%; 7 studies), and in “vascular surgery patients” was 61% (95%CI 47%, 74%, 3 studies). Only one study reported prevalence of cognitive impairment in LEAD patients alone of 19% (95%CI 14%, 24%). Quality of evidence was moderate to very low. Conclusions Cognitive impairment is highly prevalent in vascular surgery patients highlighting the need for close collaboration between vascular surgeons and geriatricians.

An emerging novel therapeutic agent for major depressive disorder, minocycline, has the potential to influence both gut microbiome and inflammatory status. The present study showed that chronic high fat diet feeding led to changes in both behaviour and the gut microbiome in male mice, without an overt inflammatory response. The diet-induced behavioural changes were characterised as increased immobility in the forced swim test and changes in locomotor activities in the open field test. Minocycline significantly altered the gut microbiome, rendering a community distinctly different to both untreated healthy and diet-affected states. In contrast, minocycline did not reverse high fat diet-induced changes in behaviour.

AIMS The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P

OBJECTIVE The impact of major affective disorders on the effectiveness of diabetes prevention programs at promoting health behaviors has not been established. We investigated whether depression modifies the effectiveness of two pragmatic diabetes prevention programs at promoting increased physical activity. RESEARCH DESIGN AND METHODS This study pooled data from two cluster randomized controlled trials (Walking Away from Type 2 Diabetes and Let’s Prevent Type 2 Diabetes) that included individuals at high risk of type 2 diabetes who were recruited from primary care. The trials used very similar intervention methods to promote physical activity and had annual follow-up over a 36-month period. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale, and physical activity was measured by a piezoelectric pedometer (Let’s Prevent Type 2 Diabetes) or an accelerometer (Walking Away from Type 2 Diabetes) and expressed as steps per day. RESULTS This analysis included 1,163 individuals (571 control, 592 intervention) who had concurrent baseline and follow-up data for ambulatory activity, depression, and anxiety. The median depression score was 3 at baseline; 11% of individuals were classified as having mild to severe depression. Those with no depressive symptoms at baseline or during follow-up increased their ambulatory activity by 592 steps per day (P < 0.001); this effect decayed by 88 steps per day (95% CI 21, 155) for every additional depressive symptom score at baseline, and each increase in the depressive symptom score between baseline and follow-up further attenuated the intervention effect by 99 steps per day (95% CI 2, 196). CONCLUSIONS Both depressive symptom burden at baseline and change in this burden are associated with a graded reduction in the effectiveness of diabetes prevention programs at increasing physical activity in primary care.

ObjectivesTo profile sleep duration and sleep efficiency in UK long-distance heavy goods vehicle (HGV) drivers and explore demographic, occupational and lifestyle predictors of sleep.MethodsCross-sectional analyses were carried out on 329 HGV drivers (98.5% men) recruited across an international logistics company within the midland’s region, UK. Sleep duration and efficiency were assessed via wrist-worn accelerometry (GENEActiv) over 8 days. Proportions of drivers with short sleep duration (Results58% of drivers had a mean sleep duration of ConclusionsThe high prevalence of short sleep duration and insufficient sleep quality (efficiency) rate suggest that many HGV drivers have increased risk of excessive daytime sleepiness, road traffic accidents and chronic disease. Future sleep research in UK HGV cohorts is warranted given the road safety and public health implications.

Background Physical activity is associated with a reduced risk of type 2 diabetes and cardiovascular disease but limited evidence exists for the sustained promotion of increased physical activity within diabetes prevention trials. The aim of the study was to investigate the long-term effectiveness of the Walking Away programme, an established group-based behavioural physical activity intervention with pedometer use, when delivered alone or with a supporting mHealth intervention. Methods Those at risk of diabetes (nondiabetic hyperglycaemia) were recruited from primary care, 2013–2015, and randomised to (1) Control (information leaflet); (2) Walking Away (WA), a structured group education session followed by annual group-based support; or (3) Walking Away Plus (WAP), comprising WA annual group-based support and an mHealth intervention delivering tailored text messages supported by telephone calls. Follow-up was conducted at 12 and 48 months. The primary outcome was accelerometer measured ambulatory activity (steps/day). Change in primary outcome was analysed using analysis of covariance with adjustment for baseline, randomisation and stratification variables. Results One thousand three hundred sixty-six individuals were randomised (median age = 61 years, ambulatory activity = 6638 steps/day, women = 49%, ethnic minorities = 28%). Accelerometer data were available for 1017 (74%) individuals at 12 months and 993 (73%) at 48 months. At 12 months, WAP increased their ambulatory activity by 547 (97.5% CI 211, 882) steps/day compared to control and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of moderate-to-vigorous physical activity. Differences were not maintained at 48 months. WA was no different to control at 12 or 48 months. Secondary anthropometric and health outcomes were largely unaltered in both intervention groups apart from small reductions in body weight in WA (~ 1 kg) at 12- and 48-month follow-up. Conclusions Combining a pragmatic group-based intervention with text messaging and telephone support resulted in modest changes to physical activity at 12 months, but changes were not maintained at 48 months. Trial registration ISRCTN 83465245 (registered on 14 June 2012).

IntroductionThe COVID-19 pandemic has resulted in significant morbidity and mortality, and has devastated economies in many countries. Amongst the groups identified as being at increased risk from COVID-19 are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related physical and mental health outcomes. To date there has been no large-scale analysis of these risks in UK healthcare workers or ancillary workers in healthcare settings, stratified by ethnicity or occupation type, and adjusted for potential confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).Methods and analysisA baseline questionnaire with follow-up questionnaires at 4 and 8 months will be administered to a national cohort of UK healthcare workers and ancillary workers in healthcare settings, and those registered with UK healthcare regulators. With consent, data will be linked to health records, and participants followed up for 25 years.Univariate associations between ethnicity and primary outcome measures (clinical COVID-19 outcomes, and physical and mental health) and key confounders/explanatory variables will be tested, followed by multivariable analyses to test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables, with interactions included as appropriate. Using follow-up data, multilevel models will be used to model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.Ethics and disseminationThe study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk to participants. We aim to manage the small risk of participant distress due to being asked questions on sensitive topics by clearly indicating on the participant information sheet that the questionnaire covers sensitive topics and that participants are under no obligation to answer these, or indeed any other, questions, and by providing links to support organisations. Results will be disseminated with reports to Government and papers uploaded to pre-print servers and submitted to peer reviewed journals.Registration detailsTrial ID: ISRCTN11811602STRENGTHS AND LIMITATIONS OF THIS STUDYNational, UK-wide, study, aiming to capture variety of healthcare worker job roles including ancillary workers in healthcare settings.Longitudinal study including three waves of questionnaire data collection, and linkage to administrative data over 25 years, with consent.Unique support from all major UK healthcare worker regulators, relevant healthcare worker organisations, and a Professional Expert Panel to increase participant uptake and the validity of findings.Potential for self-selection bias and low response rates, and the use of electronic invitations and online data collection makes it harder to reach ancillary workers without regular access to work email addresses.

AimTo assess the effectiveness of a low-cost pragmatic intervention (structured education and ongoing text message support) to increase daily physical activity in participants 12–48 months after a coronary heart disease cardiac event (myocardial infarction, angina or acute coronary syndrome) diagnosis.MethodsA single-centre randomised controlled trial of 291 adults randomised to a structured education programme (n=145) or usual care (n=146). The programme consisted of two 2.5 hour sessions delivered 2 weeks apart, followed by supplementary text message support. The GENEActiv accelerometer assessed the primary outcome at 12 months (change in overall physical activity (expressed in milli gravitational (mg) units) from baseline). Secondary outcomes included anthropometric, physical function, cardiovascular, biochemical and patient-reported outcome measures. Linear regression was used to compare outcome measures between groups on a modified intention-to-treat basis.ResultsParticipants’ mean age was 66.5±9.7 years, 84.5% males, 82.5% white British and 15.5% south Asian. At 12 months, there was no difference between the groups in terms of change in overall physical activity (−0.23 mg (95% CI −1.22 to 0.75), p=0.64) and the programme was well accepted (88% attendance). Exploratory analyses showed that average moderate to vigorous physical activity (MVPA) levels increased in individuals not meeting physical activity guidelines (≥150 min per week) on enrolment compared with those who did, by 8 minutes per day (8.04 (95% CI 0.99 to 15.10), p=0.03).ConclusionThe programme was well attended but showed no change in physical activity levels. Results show high baseline MVPA levels and suggest that Physical Activity after Cardiac EventS education may benefit cardiac patients not currently meeting activity guidelines.Trial registration numberISRCTN91163727.

RXFP3 (relaxin-family peptide 3 receptor) is the cognate G-protein-coupled receptor for the neuropeptide, relaxin-3. RXFP3 is expressed widely throughout the brain, including the hypothalamus, where it has been shown to modulate feeding behavior and neuroendocrine activity in rodents. In order to better characterize its potential mechanisms of action, this study determined whether RXFP3 is expressed by dopaminergic neurons within the arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), in addition to the ventral tegmental area (VTA). Neurons that express RXFP3 were visualized in coronal brain sections from RXFP3-Cre/tdTomato mice, which express the tdTomato fluorophore within RXFP3-positive cells, and dopaminergic neurons in these areas were visualized by simultaneous immunohistochemical detection of tyrosine hydroxylase-immunoreactivity (TH-IR). Approximately 20% of ARC neurons containing TH-IR coexpressed tdTomato fluorescence, suggesting that RXFP3 can influence the dopamine pathway from the ARC to the pituitary gland that controls prolactin release. The ability of prolactin to reduce leptin sensitivity and increase food consumption therefore represents a potential mechanism by which RXFP3 activation influences feeding. A similar proportion of DMH neurons containing TH-IR expressed RXFP3-related tdTomato fluorescence, consistent with a possible RXFP3-mediated regulation of stress and neuroendocrine circuits. In contrast, RXFP3 was barely detected within the VTA. TdTomato signal was absent from the ARC and DMH in sections from Rosa26-tdTomato mice, suggesting that the cells identified in RXFP3-Cre/tdTomato mice expressed authentic RXFP3-related tdTomato fluorescence. Together, these findings identify potential hypothalamic mechanisms through which RXFP3 influences neuroendocrine control of metabolism, and further highlight the therapeutic potential of targeting RXFP3 in feeding-related disorders.

Background: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. Method: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. Results: The &ldquo, PRE-STARt&rdquo, programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. Conclusion: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging &lsquo, at risk&rsquo, groups and their families.

Although neurogenesis is affected in several psychiatric diseases, the effects and mechanisms of action of psychoactive drugs on neurogenesis remain unknown and/or controversial. This study aims to evaluate the effects of psychoactive drugs on the expression of genes involved in neurogenesis. Neuronal-like cells (NT2-N) were treated with amisulpride (10 &micro, M), aripiprazole (0.1 &micro, M), clozapine (10 &micro, M), lamotrigine (50 &micro, M), lithium (2.5 mM), quetiapine (50 &micro, M), risperidone (0.1 &micro, M), or valproate (0.5 mM) for 24 h. Genome wide mRNA expression was quantified and analysed using gene set enrichment analysis, with the neurogenesis gene set retrieved from the Gene Ontology database and the Mammalian Adult Neurogenesis Gene Ontology (MANGO) database. Transcription factors that are more likely to regulate these genes were investigated to better understand the biological processes driving neurogenesis. Targeted metabolomics were performed using gas chromatography-mass spectrometry. Six of the eight drugs decreased the expression of genes involved in neurogenesis in both databases. This suggests that acute treatment with these psychoactive drugs negatively regulates the expression of genes involved in neurogenesis in vitro. SOX2 and three of its target genes (CCND1, BMP4, and DKK1) were also decreased after treatment with quetiapine. This can, at least in part, explain the mechanisms by which these drugs decrease neurogenesis at a transcriptional level in vitro. These results were supported by the finding of increased metabolite markers of mature neurons following treatment with most of the drugs tested, suggesting increased proportions of mature relative to immature neurons consistent with reduced neurogenesis.

ObjectiveUsing primary care data, develop and validate sex-specific prognostic models that estimate the 10-year risk of people with non-diabetic hyperglycaemia developing type 2 diabetes.DesignRetrospective cohort study.SettingPrimary care.Participants154 705 adult patients with non-diabetic hyperglycaemia.Primary outcomeDevelopment of type 2 diabetes.MethodsThis study used data routinely collected in UK primary care from general practices contributing to the Clinical Practice Research Datalink. Patients were split into development (n=109 077) and validation datasets (n=45 628). Potential predictor variables, including demographic and lifestyle factors, medical and family history, prescribed medications and clinical measures, were included in survival models following the imputation of missing data. Measures of calibration at 10 years and discrimination were determined using the validation dataset.ResultsIn the development dataset, 9332 patients developed type 2 diabetes during 293 238 person-years of follow-up (31.8 (95% CI 31.2 to 32.5) per 1000 person-years). In the validation dataset, 3783 patients developed type 2 diabetes during 115 113 person-years of follow-up (32.9 (95% CI 31.8 to 33.9) per 1000 person-years). The final prognostic models comprised 14 and 16 predictor variables for males and females, respectively. Both models had good calibration and high levels of discrimination. The performance statistics for the male model were: Harrell’s C statistic of 0.700 in the development and 0.701 in the validation dataset, with a calibration slope of 0.974 (95% CI 0.905 to 1.042) in the validation dataset. For the female model, Harrell’s C statistics were 0.720 and 0.718, respectively, while the calibration slope was 0.994 (95% CI 0.931 to 1.057) in the validation dataset.ConclusionThese models could be used in primary care to identify those with non-diabetic hyperglycaemia most at risk of developing type 2 diabetes for targeted referral to the National Health Service Diabetes Prevention Programme.

Background Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2. Methods We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown. Findings 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p

OBJECTIVE To describe and critique tools used to assess frailty in vascular surgery patients, and investigate its associations with patient factors and outcomes. BACKGROUND Increasing evidence shows negative impacts of frailty on outcomes in surgical patients, but little investigation of its associations with patient factors has been undertaken. METHODS Systematic review and meta-analysis of studies reporting frailty in vascular surgery patients (PROSPERO registration: CRD42018116253) searching Medline, Embase, CINAHL, PsycINFO, and Scopus. Quality of studies was assessed using Newcastle-Ottawa scores (NOS) and quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria. Associations of frailty with patient factors were investigated by difference in means (MD) or expressed as risk ratios (RRs), and associations with outcomes expressed as odds ratios (ORs) or hazard ratios (HRs). Data were pooled using random-effects models. RESULTS Fifty-three studies were included in the review and only 8 (15%) were both good quality (NOS ≥ 7) and used a well-validated frailty measure. Eighteen studies (62,976 patients) provided data for the meta-analysis. Frailty was associated with increased age [MD 4.05 years; 95% confidence interval (CI) 3.35, 4.75], female sex (RR 1.32; 95% CI 1.14, 1.54), and lower body mass index (MD -1.81; 95% CI -2.94, -0.68). Frailty was associated with 30-day mortality [adjusted OR (AOR) 2.77; 95% CI 2.01-3.81), postoperative complications (AOR 2.16; 95% CI 1.55, 3.02), and long-term mortality (HR 1.85; 95% CI 1.31, 2.62). Sarcopenia was not associated with any outcomes. CONCLUSION Frailty, but not sarcopenia, is associated with worse outcomes in vascular surgery patients. Well-validated frailty assessment tools should be preferred clinically, and in future research.

Background The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study’s objectives were therefore to externally validate the KFRE’s prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services. Methods and findings Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (, In this cohort study, Rupert Major and colleagues evaluate the performance of the Kidney Failure Risk Equation in chronic kidney disease patients in primary care settings and project impact of a recalibrated equation on referral practices and patient outcomes., Author summary Why was this study done? The Kidney Failure Risk Equation (KFRE) has been developed in multinational chronic kidney disease (CKD) cohorts to predict end stage renal disease (ESRD) events (the need for dialysis or a kidney transplant) over 2- and 5-year time periods. The performance of the KFRE has not been extensively tested in UK and European primary care CKD populations. The projected impact of the KFRE on referrals from primary to secondary care has not been studied, and it is unclear what criteria for referrals should be used. What did the researchers do and find? Our study suggests that the KFRE has largely accurate performance (discrimination) for predicting ESRD, but requires adjustment (recalibration) for a primary care setting. Compared to current referral criteria, using hybrid criteria of a ≥5% risk of ESRD over 5 years from the recalibrated KFRE and/or a urine albumin-to-creatinine ratio (ACR) of ≥70 mg/mmol would reduce the number of individuals eligible for referral without increasing the number who later develop ESRD and are not initially eligible for referral. What do these findings mean? The recalibrated KFRE can be used to predict the risk of ESRD over 2 and 5 years in primary care CKD. The KFRE, in conjunction with the ACR criterion, can be used to triage CKD referrals from primary to secondary care.

Background and Aims There are fewer trials conducted in nephrology than any other speciality. Many trials fail to recruit to target and are therefore underpowered, resulting in unclear evidence and unlikely to be implemented into clinical practice. Carefully designed trials could improve the treatment options for haemodialysis patients. These could include designs other than individually randomised parallel group designs. We have reviewed cluster, stepped wedge and crossover randomised trials carried out in prevalent haemodialysis patients. Method A search for randomised controlled trials (RCTs) in haemodialysis patients was conducted across five databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) in October 2019. The first publication of a stepped wedge trial in haemodialysis was in 2013, so we searched from 2013-2019. Inclusion criteria were RCTs including adults receiving at least 3 months of haemodialysis. Once eligible studies were identified, we compared the sample size sections to the CONSORT requirements and extracted data on these parameters and assessed recruitment targets, attrition rates and primary outcome result. Results We identified 911 RCTs of which 13 (1.4%) cluster randomised trials, including one stepped wedge, and 145 (15.9%) crossover trials were identified. Data were extracted for 10 randomly selected crossover trials. The total sample size required was not reported in 46% (n=6) cluster trials and 60% (n=6) crossover trials, with only 37.5% (n=3) of cluster trials and 50% (n=4) of crossover trials providing a justification for their sample size. In cluster trials, 13% (n=1) stated number of clusters required and 25% (n=2) gave the average cluster size, none of these stated the anticipated variance in cluster size and only 12.5% (n=1) stated the intracluster correlation (ICC) used to calculate the sample size, with none taking into account uncertainty in ICC. In 31% (n=4) of the cluster trials, the dialysis centre was the cluster and in the other 69% (n=9), the dialysis shift was the cluster. For crossover trials, within participant variability was only accounted for in 12.5% (n=1) of trials. A CONSORT flow diagram was reported in 70% of the trials assessed, with 39% recruiting to target. There were also some differences seen between crossover and cluster designs. The average number of participants at the start of a cluster trial was 470, compared to 26 in crossover trials. Where able to assess, cluster trials had an average attrition rate of 25% this was lower in crossover trials, where the average attrition rate was 14%. Eighty five percent (n=11) of cluster trials had a primary outcome reaching statistical significance, however only 20% (n=2) of crossover trials reached statistical significance. Conclusion Cluster and crossover randomised trials are poorly reported. There was insufficient information provided for sample size calculations to be replicated in majority of trials. The average attrition rate was low in crossover trials, however a large proportion of these trials did not have a primary outcome reaching statistical significance, suggesting these trials could have been underpowered. Improvements in the design, conduct and reporting of cluster and crossover trials in the haemodialysis population is urgently required.

Objective: Walking Away from Diabetes (Walking Away) is a low resource 3-hour group-based behavioural intervention designed to promote physical activity through pedometer use in those with prediabetes. This trial aimed to investigate whether Walking Away leads to sustained increases in physical activity when delivered with and without an integrated mHealth intervention compared to control. Methods: Those with a history of prediabetes (HbA1c ≥42 [6.0], Results: 1366 individuals were randomised (median age = 61 years, BMI = 28.4 kg/m2, ambulatory activity = 6638 steps/day, women = 49%, black and minority ethnicity = 28%). Accelerometer data were available for 1017 (74%) and 993 (73%) individuals at 12 and 48 months, respectively. At 12 months, WA+ increased their ambulatory activity by 547 (97.5% CI, 211, 882) steps/day compared to CON and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of MVPA. However, differences were not sustained at 48 months. There were no differences between WA and CON at 12 or 48 months. Conclusion: Combining a physical activity intervention with text messaging and telephone support resulted in modest, but clinically meaningful, changes in physical activity at 12 months, but changes are not sustained after 48 months. Disclosure K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp 0026& Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. S. Griffin: Speaker’s Bureau; Self; AstraZeneca, Napp Pharmaceuticals. Other Relationship; Self; Eli Lilly and Company. M.J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi, Sanofi US. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Other Relationship; Self; Ingeus UK. H.C. Eborall: None. C. Edwardson: None. W. Hardeman: None. J. Henson: None. S. Sharp: None. S. Sutton: None. J. Troughton: None. T. Yates: Research Support; Self; AstraZeneca. Other Relationship; Self; Ingeus UK. Funding National Institute for Health Research

Background Structured self-management education (SSME) for people with type 2 diabetes mellitus (T2DM) improves biomedical and psychological outcomes, whilst being cost-effective. Yet uptake in the UK remains low. An ‘Embedding Package’ addressing barriers and enablers to uptake at patient, health care professional and organisational levels has been developed. The aim of this study was to test the feasibility of conducting a subsequent randomised controlled trial (RCT) to evaluate the Embedding Package in primary care, using a mixed methods approach. Methods A concurrent mixed methods approach was adopted. Six general practices in the UK were recruited and received the intervention (the Embedding Package). Pseudonymised demographic, biomedical and SSME data were extracted from primary care medical records for patients recorded as having a diagnosis of T2DM. Descriptive statistics assessed quantitative data completeness and accuracy. Quantitative data were supplemented and validated by a patient questionnaire, for which two recruitment methods were trialled. Where consent was given, the questionnaire and primary care data were linked and compared. The cost of the intervention was estimated. An integrated qualitative study comprising ethnography and stakeholder and patient interviews explored the process of implementation, sustainability of change and ‘fit’ of the intervention. Qualitative data were analysed using a thematic framework guided by the Normalisation Process Theory (NPT). Results Primary care data were extracted for 2877 patients. The primary outcome for the RCT, HbA1c, was over 90% complete. Questionnaires were received from 423 (14.7%) participants, with postal invitations yielding more participants than general practitioner (GP) prompts. Ninety-one percent of questionnaire participants consented to data linkage. The mean cost per patient for the Embedding Package was £8.94, over a median follow-up of 162.5 days. Removing the development cost, this reduces to £5.47 per patient. Adoption of ethnographic and interview methods in the collection of data was appropriate, and the use of NPT, whilst challenging, enhanced the understanding of the implementation process. The need to delay the collection of patient interview data to enable the intervention to inform patient care was highlighted. Conclusions It is feasible to collect data with reasonable completeness and accuracy for the subsequent RCT, although refinement to improve the quality of the data collected will be undertaken. Based on resource use data collected, it was feasible to produce cost estimates for each individual component of the Embedding Package. The methods chosen to generate, collect and analyse qualitative data were satisfactory, keeping participant burden low and providing insight into potential refinements of the Embedding Package and customisation of the methods for the RCT. Trial registration ISRCTN, ISRCTN21321635, Registered 07/07/2017—retrospectively registered.

Background: Tight, targeted control of modifiable cardiovascular risk factors can reduce cardiovascular complications and mortality in individuals with type 2 diabetes (T2DM) and microalbuminuria. The effects of using an electronic “Prompt” with a treatment algorithm to support a treat-to-target approach has not been tested in primary care. Methods: A multi-centre, cluster-randomised trial among primary care practices across Leicestershire, UK. Primary outcome was proportion of individuals achieving systolic and diastolic blood pressure ( Results: 2721 individuals from 22 practices, mean age 63 years, 41% female, 62% from Black and Minority Ethnic groups, completed two years follow-up. There were no significant differences in the proportion of individuals achieving the composite primary outcome, although the proportion of individuals achieving the pre-specified outcome of total cholesterol Conclusions: Greater improvements in composite cardiovascular risk factor control with this intervention compared to standard care were not achieved in this cohort of high-risk individuals with T2DM. However, improvements in lipid profile and coding can benefit patients with diabetes to alter the high risk of atherosclerotic cardiovascular events. Future studies should consider comprehensive strategies including patient education and healthcare professional engagement, in the management of T2DM.

Background Office-based workers accumulate high amounts of sitting time. Stand More At Work (SMArT Work) aimed to reduce occupational sitting time and a cluster randomised controlled trial demonstrated it was successful in achieving this aim. The purpose of this paper is to present the process evaluation of the SMArT Work intervention. Methods Questionnaire data were collected from intervention participants at 6 months (n = 58) and 12 months (n = 55). Questionnaires sought feedback on the different components of the intervention (education, height-adjustable desk, Darma cushion, behaviour feedback, progress chats (coaching) with research team, action planning/goal setting diary) and experiences of evaluation measures. Control participants (n = 37) were asked via questionnaire at 12-month follow-up about the impact of the study on their behaviour and any lifestyle changes made during the study. Participants from both arms were invited to focus groups to gain a deeper understanding of their experiences on completion of 12-month follow-up. Results Focus group and questionnaire data showed a positive attitude towards the height-adjustable workstation with a high proportion of participants using it every day (62%). Most participants (92%) felt the education seminar increased their awareness of the health consequences of too much sitting and motivated them to change their behaviour. Receiving feedback on their sitting time and support from the research team also encouraged behaviour change. The Darma cushion and action planning/goal setting diary were seen to be less helpful for behaviour change. Benefits experienced included fewer aches and pains, improved cognitive functioning, increased productivity, more energy and positive feelings about general health. Conclusions Key elements of the programme identified as facilitating behaviour change were the educational seminar, the height-adjustable workstation, behavioural feedback and regular contact with research staff through regular progress chats. Trial registration ISRCTN: ISRCTN10967042. Registered on 2 February 2015.

IntroductionDue to the anti-inflammatory, antioxidant and anti-apoptotic properties of minocycline, clinical trials have evaluated the potential of this drug to treat several psychiatric and neurological disorders, including major depressive disorder, schizophrenia, bipolar disorder, stroke and amyotrophic lateral sclerosis. This protocol proposes a systematic review (and potential meta-analysis) that aims to identify and critically evaluate randomised controlled trials of minocycline for treating psychiatric and neurological disorders.Methods and analysisPubMed, Embase, Cochrane Central Register of Controlled Clinical Trials, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be used to identify randomised controlled trials that used minocycline to treat psychiatric and neurological disorders. Double-blind, randomised, controlled, clinical trials of participants aged 18 years or older and written in English will be included in the review. Data will be extracted by two independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed and the Cochrane Collaboration’s ‘Risk of Bias’ tool will be used to assess the risk of bias in all studies included in the systematic review. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to access the overall quality of the level of evidence of the studies. If sufficient evidence is identified, a meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. Heterogeneity of evidence will be evaluated using the I2model.Ethics and disseminationThis systematic review will evaluate only published data; therefore, ethical approval is not required. The systematic review will be published in a peer-reviewed journal and presented at relevant research conferences.Trial registration numberCRD42020153292.