Debate: Are surrogate end-point studies worth the effort?

Surrogate end-points of cardiovascular disease can provide useful information in cross-sectional, prospective and interventional studies. They provide information on association with risk factors, natural history and factors associated with disease progression. Because every participant can reach an end-point, sufficient power can be attained with much smaller numbers of subjects in surrogate end-point studies than in studies that use clinical endpoints, so that the costs are likely to be substantially less. Measures of carotid intima-media thickness (IMT) by B-mode ultrasonography and of coronary calcification by electron beam computed tomography (EBCT) appear to be the most promising surrogate end-points

Evaluation of the effect of nurse education on patient-reported foot checks and foot care behaviour of people with diabetes receiving haemodialysis

AIMS: To assess whether a programme of nurse education increased the frequency with which nurses conducted foot checks on people with diabetes undergoing haemodialysis and to evaluate whether this influenced self-reported foot care behaviour. METHODS:A non-randomized stepped-wedge design was used to evaluate a nurse education programme implemented in four UK National Health Service dialysis units. People with diabetes undergoing haemodialysis were invited to complete a questionnaire on the frequency of foot examination by health professionals, on the presence of foot problems and on their own foot care behaviour, using the Nottingham Assessment of Functional Foot-care (NAFF). An education session for nurses, including procedures for foot examination, was conducted sequentially in each of four haemodialysis units. The questionnaire was repeated at 2-monthly intervals. RESULTS:The education session resulted in a significant increase in the reported number of foot examinations by nurses (P = 0.007). There was also a significant improvement in reported foot care behaviour (P < 0.001), but this occurred between the first and second 2-monthly assessments and was unrelated to the timing of the intervention. CONCLUSIONS: A single education session can improve the routine checking of the feet of people with diabetes undergoing haemodialysis. The administration of the Nottingham Assessment of Functional Foot-care questionnaire was associated with improved self-reported foot care behaviour, reflecting greater awareness of risk in this population

Obesity as a risk factor for severe COVID-19: summary of the best evidence and implications for health care

Purpose of Review: To collate the best evidence from several strands—epidemiological, genetic, comparison with historical data and mechanistic information—and ask whether obesity is an important causal and potentially modifiable risk factor for severe COVID-19 outcomes. Recent Findings: Several hundred studies provide powerful evidence that body mass index (BMI) is a strong linear risk factor for severe COVID-19 outcomes, with recent studies suggesting ~5-10% higher risk for COVID-19 hospitalisation per every kg/m2 higher BMI. Genetic data concur with hazard ratios increasing by 14% per every kg/m2 higher BMI. BMI to COVID-19 links differ markedly from prior BMI-infection associations and are further supported as likely causal by multiple biologically plausible pathways. Summary: Excess adiposity appears to be an important, modifiable risk factor for adverse COVID-19 outcomes across all ethnicities. The pandemic is also worsening obesity levels. It is imperative that medical systems worldwide meet this challenge by upscaling investments in obesity prevention and treatments

VEGF is indirectly associated with NO production

Background? Increased levels of vascular endothelial growth factor (VEGF) have been observed in patients with metabolic syndrome (MetS). Nitric oxide (NO) formation is reduced in MetS, but its relationship to VEGF production remains poorly defined. We evaluated the association between VEGF/NO synthesis and insulin sensitivity in obese subjects and investigated the secretory response of VEGF to an acute elevation of glucose.Materials and methods? Seven healthy normal-weight subjects, seven obese subjects without MetS and seven obese subjects with MetS were recruited. Anthropometry, body composition and cardiometabolic functions (blood pressure, glucose, insulin, triglycerides, total cholesterol, HDL-C and VEGF) were measured, and a novel stable isotope method was used to assess in vivo rates of NO production. A frequent sampling intravenous glucose tolerance test was performed to study the dynamics of VEGF release.Results? Fasting VEGF levels were significantly higher in the two obese groups compared to the control group (P for trend = 0·02), but the difference was not significant after adjustment for age. Vascular endothelial growth factor levels were associated with systolic blood pressure (? = 0·54; P = 0·01) and NO production (? = ?0·44; P = 0·04). Vascular endothelial growth factor levels increased in response to acute hyperglycaemia in normal-weight and obese subjects (P &lt; 0·001).Conclusions? Vascular endothelial growth factor levels rapidly increase during hyperglycaemia and are inversely related to NO production at steady state. The potential link between the acute secretion of VEGF and atherosclerotic risk in subjects with poorly controlled glycaemia as well as the potential of lowering elevated VEGF levels by increasing NO production and/or availability warrants further investigation

Evaluation of the digital diabetes prevention programme pilot: Uncontrolled mixed-methods study protocol

This is the final version. Available from the publisher via the DOI in this record.Introduction The prevalence of type 2 diabetes is rising steeply. National Health Service England (NHSE) is exploring the potential of a digital diabetes prevention programme (DDPP) and has commissioned a pilot with embedded evaluation. Methods and analysis This study aims to determine whether, and if so, how, should NHSE implement a national DDPP, using a mixed-methods pretest and post-test design, underpinned by two theoretical frameworks: the Coventry, Aberdeen and London - Refined (CALO-RE) taxonomy of behavioural change techniques for the digital interventions and the Consolidated Framework for Implementation Research (CFIR) for implementation processes. In eight pilot areas across England, adults with non-diabetic hyperglycaemia (NDH) (glycated haemoglobin (HbA1c) 42-47 mmol/mol or fasting plasma glucose 5.5-6.9 mmol/L) and adults without NDH who are overweight (body mass index (BMI) >25 kg/m 2) or obese (BMI >30 kg/m 2) will be referred to one of five digitally delivered diabetes prevention interventions. The primary outcomes are reduction in HbA1c and weight (for people with NDH) and reduction in weight (for people who are overweight or obese) at 12 months. Secondary outcomes include use of the intervention, satisfaction, physical activity, patient activation and resources needed for successful implementation. Quantitative data will be collected at baseline, 6 months and 12 months by the digital intervention providers. Qualitative data will be collected through semistructured interviews with commissioners, providers, healthcare professionals and patients. Quantitative data will be analysed descriptively and using generalised linear models to determine whether changes in outcomes are associated with demographic and intervention factors. Qualitative data will be analysed using framework analysis, with data pertaining to implementation mapped onto the CFIR. Ethics and dissemination The study has received ethical approval from the Public Health England Ethics and Research Governance Group (reference R&D 324). Dissemination will include a report to NHSE to inform future policy and publication in peer-reviewed journals.National Institute for Health Research (NIHR

Financial disincentives? A three-armed randomised controlled trial of the effect of financial Incentives in Diabetic Eye Assessment by Screening (IDEAS) trial

Objective Conflicting evidence exists regarding the impact of financial incentives on encouraging attendance at medical screening appointments. The primary aim was to determine whether financial incentives increase attendance at diabetic eye screening in persistent non-attenders. Methods and analysis A three-armed randomised controlled trial was conducted in London in 2015. 1051 participants aged over 16 years, who had not attended eye screening appointments for 2 years or more, were randomised (1.4:1:1 randomisation ratio) to receive the usual invitation letter (control), an offer of £10 cash for attending screening (fixed incentive) or a 1 in 100 chance of winning £1000 (lottery incentive) if they attend. The primary outcome was the proportion of invitees attending screening, and a comparative analysis was performed to assess group differences. Pairwise comparisons of attendance rates were performed, using a conservative Bonferroni correction for independent comparisons. Results 34/435 (7.8%) of control, 17/312 (5.5%) of fixed incentive and 10/304 (3.3%) of lottery incentive groups attended. Participants who received any incentive were significantly less likely to attend their appointment compared with controls (risk ratio (RR)=0.56; 95% CI 0.34 to 0.92). Those in the probabilistic incentive group (RR=0.42; 95% CI 0.18 to 0.98), but not the fixed incentive group (RR=1.66; 95% CI 0.65 to 4.21), were significantly less likely to attend than those in the control group. Conclusion Financial incentives, particularly lottery-based incentives, attract fewer patients to diabetic eye screening than standard invites in this population. Financial incentives should not be used to promote screening unless tested in context, as they may negatively affect attendance rates

Incentives in diabetic eye assessment by screening (IDEAS): study protocol of a three-arm randomized controlled trial using financial incentives to increase screening uptake in London

Background: Diabetes is an increasing public health problem in the UK and globally. Diabetic retinopathy is a microvascular complication of diabetes, and is one of the leading causes of blindness in the UK working age population. The diabetic eye screening programme in England aims to invite all people with diabetes aged 12 or over for retinal photography to screen for the presence of diabetic retinopathy. However, attendance rates are only 81 %, leaving many people at risk of preventable sight loss. Methods: This is a three arm randomized controlled trial to investigate the impact of different types of financial incentives (based on principles from behavioral economics) on increasing attendance at diabetic eye screening appointments in London. Eligible participants will be aged 16 or over, and are those who have been invited to screening appointments annually, but who have not attended, or telephoned to rearrange an appointment, within the last 24 months. Eligible participants will be randomized to one of three conditions: 1. Control condition (usual invitation letter) 2. Fixed incentive condition (usual invitation letter, including a voucher for £10 if they attend their appointment) 3. Probabilistic incentive condition (invitation letter, including a voucher for a 1 in 100 chance of winning £1000 if they attend their appointment). Participants will be sent invitation letters, and the primary outcome will be whether or not they attend their appointment. One thousand participants will be included in total, randomized with a ratio of 1.4:1:1. In order to test whether the incentive scheme has a differential impact on patients from different demographic or socio-economic groups, information will be recorded on age, gender, distance from screening center, socio-economic status and length of time since they were last screened. A cost-effectiveness analysis will also be performed. Discussion: This study will be the first trial of financial incentives for improving uptake of diabetic eye screening. If effective, the intervention may suggest a cost-effective way to increase screening rates, thus reducing unnecessary blindness

Uptake and impact of the English National Health Service digital diabetes prevention programme: observational study

INTRODUCTION: 'Healthier You', the National Health Service (NHS) diabetes prevention programme (DPP) offers adults in England at high risk of type 2 diabetes (T2DM) an evidence-based behavioral intervention to prevent or delay T2DM onset. This study assesses the impact of a pilot digital stream of the DPP (DDPP) on glycated hemoglobin (HbA1c) and weight. RESEARCH DESIGN AND METHODS: A service evaluation employing prospectively collected data in a prospective cohort design in nine NHS local pilot areas across England. Participants were adults with non-diabetic hyperglycemia (NDH) (HbA1c 42-47 mmol/mol or fasting plasma glucose 5.5-6.9 mmol/L) in the 12 months prior to referral. The DDPP comprised five digital health interventions (DHI). Joint primary outcomes were changes in HbA1c and weight between baseline and 12 months. HbA1c and weight readings were recorded at referral (baseline) by general practices, and then at 12-month postregistration. Demographic data and service variables were collected from the DHI providers. RESULTS: 3623 participants with NDH registered for the DDPP and of these, 2734 (75%) were eligible for inclusion in the analyses. Final (12-month) follow-up data for HbA1c were available for 1799 (50%) and for weight 1817 (50%) of registered participants. Mean change at 12 months was -3.1 (-3.4 to -2.8) kg, p<0.001 for weight and -1.6 (-1.8 to -1.4) mmol/mol, p<0.001 for HbA1c. Access to peer support and a website and telephone service was associated with significantly greater reductions in HbA1c and weight. CONCLUSIONS: Participation in the DDPP was associated with clinically significant reductions in weight and HbA1c. Digital diabetes prevention can be an effective and wide-reaching component of a population-based approach to addressing type 2 diabetes prevention

Care processes in people in remission from type 2 diabetes:A cohort study using the National Diabetes Audit

Aims: People with type 2 diabetes can enter remission but may relapse or develop legacy complications. This analysis assesses whether people with remission from type 2 diabetes continue receiving annual care processes recommended in national guidelines and the potential impacts of formal recognition of remission. Methods: People with type 2 diabetes with and without formal recognition (diagnostic code) of remission, and with and without evidence of remission (HbA1c &lt; 48 mmol/mol without prescription for glucose-lowering drugs in preceding 26 weeks), included in the 2018/19 National Diabetes Audit (NDA) for England and Wales were followed up to identify care processes received between 1 January 2019 and 31 March 2020. Results: Of the 2,822,145 people with type 2 diabetes in the cohort, 16,460 (0.58%) were coded with remission in the 2018/19 NDA. After adjustment for age, sex, socioeconomic deprivation and ethnicity, people coded with remission were less likely to receive each care process than those without such coding irrespective of HbA1c measurements (relative risk (RR) of receiving all 8 care processes 0.70 (95% CI 0.69–0.72)). For the 339,235 people with evidence of remission, irrespective of diagnostic coding compared to those without such evidence, the RR for receiving all 8 care processes was 0.94 (95% CI 0.93–0.94). Conclusions: People coded with remission of type 2 diabetes were less likely to receive diabetes care processes than those without such coding. People with evidence of remission had only a slightly reduced likelihood of receiving care processes. Formal recognition of remission may affect the provision or uptake of care processes