Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Diet and physical activity interventions to improve cardiovascular disease risk factors in liver transplant recipients: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions. METHODS: We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis. RESULTS: Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low. CONCLUSION: Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care.

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices.

AIMS: There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact ('remote') or via in-person appointments in primary care and explored impact of age on screening outcomes. METHODS AND RESULTS: People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1-4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. CONCLUSION: Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over.

Prospective associations between changes in physical activity and sedentary time and subsequent lean muscle mass in older English adults: the EPIC-Norfolk cohort study.

BACKGROUND: The longitudinal associations between physical behaviours and lean muscle mass indices need to be better understood to aid healthy ageing intervention development. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers. We also assessed domain-specific physical behaviours (walking, cycling, gardening and housework time) with self-report questionnaires at baseline (2006-2011) and follow-up (2012-2016) in the European Prospective Investigation into Cancer (EPIC)-Norfolk study. We assessed body composition using dual-energy X-ray absorptiometry (DEXA) at follow-up in 1535 participants (≥ 60 years at baseline). From this, we derived appendicular lean muscle mass (ALM) indices (% relative ALM = (ALM/total body weight)*100), body mass index (BMI)-scaled ALM (ALM/BMI, kg/kg/m2) and height-scaled ALM (ALM/height2, kg/m2)). We evaluated the prospective associations of both baseline and change in physical behaviours with follow-up muscle mass indices using multivariable linear regression. RESULTS: Over 5.5 years (SD 14.8) follow-up, higher baseline accelerometer-measured physical activity and lower sedentary time were associated with higher subsequent relative ALM and BMI-scaled ALM, but not height-scaled ALM (e.g. 0.02% higher subsequent relative ALM per minute/day of baseline MVPA for men). Greater increases in physical activity and greater declines in sedentary time variables were associated with higher subsequent relative ALM and BMI-scaled ALM, but not height-scaled ALM (e.g. 0.001 kg/kg/m2 subsequent BMI-scaled ALM and 0.04% subsequent relative ALM per min/day/year increases in LPA over follow-up; 0.001 kg/kg/m2 subsequent BMI-scaled ALM and -0.03% subsequent relative ALM per min/day/year less of total sedentary time over follow-up). Greater increases in women's cycling and gardening over follow-up were associated with greater subsequent relative ALM (cycling 0.9% per hour/week/year; gardening 0.2% per hour/week/year) and BMI-scaled ALM (cycling 0.03 kg/kg/m2 per hour/week/year; gardening 0.004 kg/kg/m2 per hour/week/year). CONCLUSION: Physical behaviours across all intensities, and in women more specifically cycling and gardening, may help prevent age-related declines in muscle mass.

Evaluating the potential impact of lifestyle-based behavior change interventions delivered at the time of colorectal cancer screening.

PURPOSE: To analyze interventions implemented at the time of colorectal cancer (CRC) screening, or among individuals who have previously undergone investigation for CRC, focused on reducing CRC risk through promotion of lifestyle behavior change. Additionally, this review evaluated to what extent such interventions apply behavior change techniques (BCTs) to achieve their objectives. METHODS: Five databases were systematically searched to identify randomized control trials seeking to reduce CRC risk through behavior change. Outcomes were changes in health-related lifestyle behaviors associated with CRC risk, including changes in dietary habits, body mass index, smoking behaviors, alcohol consumption, and physical activity. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. BCT's were coded from a published taxonomy of 93 techniques. RESULTS: Ten RCT's met the inclusion criteria. Greater increase in fruit/vegetable consumption in the intervention group were observed with respect to the control (SMD 0.13, 95% CI 0.08 to 0.18; p < 0.001). Across fiber, alcohol, fat, red meat, and multivitamin consumption, and smoking behaviors, similar positive outcomes were observed (SMD 0.09-0.57 for all, p < 0.01). However, among physical activity and body mass index, no difference between the intervention groups compared with controls were observed. A median of 7.5 BCTs were applied across included interventions. CONCLUSION: While magnitude of the observed effect sizes varied, they correspond to potentially important changes in lifestyle behaviors when considered on a population scale. Future interventions should identify avenues to maximize long-term engagement to promote sustained lifestyle behavior change.

Implementation of risk stratification within bowel cancer screening: a community jury study exploring public acceptability and communication needs.

BACKGROUND: Population-based cancer screening programmes are shifting away from age and/or sex-based screening criteria towards a risk-stratified approach. Any such changes must be acceptable to the public and communicated effectively. We aimed to explore the social and ethical considerations of implementing risk stratification at three different stages of the bowel cancer screening programme and to understand public requirements for communication. METHODS: We conducted two pairs of community juries, addressing risk stratification for screening eligibility or thresholds for referral to colonoscopy and screening interval. Using screening test results (where applicable), and lifestyle and genetic risk scores were suggested as potential stratification strategies. After being informed about the topic through a series of presentations and discussions including screening principles, ethical considerations and how risk stratification could be incorporated, participants deliberated over the research questions. They then reported their final verdicts on the acceptability of risk-stratified screening and what information should be shared about their preferred screening strategy. Transcripts were analysed using codebook thematic analysis. RESULTS: Risk stratification of bowel cancer screening was acceptable to the informed public. Using data within the current system (age, sex and screening results) was considered an obvious next step and collecting additional data for lifestyle and/or genetic risk assessment was also preferable to age-based screening. Participants acknowledged benefits to individuals and health services, as well as articulating concerns for people with low cancer risk, potential public misconceptions and additional complexity for the system. The need for clear and effective communication about changes to the screening programme and individual risk feedback was highlighted, including making a distinction between information that should be shared with everyone by default and additional details that are available elsewhere. CONCLUSIONS: From the perspective of public acceptability, risk stratification using current data could be implemented immediately, ahead of more complex strategies. Collecting additional data for lifestyle and/or genetic risk assessment was also considered acceptable but the practicalities of collecting such data and how the programme would be communicated require careful consideration.

Associations between change in physical activity and sedentary time and health-related quality of life in older english adults: the EPIC-Norfolk cohort study.

BACKGROUND: No previous studies have examined the associations between changes in objectively-measured physical behaviours with follow-up QoL in older adults. Based on cross-sectional evidence, it is biologically plausible that such associations exist. If so, this bolsters the case for the commissioning of activity interventions and for including QoL as an outcome in trials of such interventions. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers at baseline (2006-2011) and follow-up (2012-2016) and health-related quality-of-life (QoL) using EQ-5D questionnaires at follow-up in 1433 participants (≥ 60 years) of the EPIC (European Prospective Investigation into Cancer)-Norfolk study. The EQ-5D summary score was used, with 0 as the worst to 1 as best perceived quality-of-life. We evaluated the prospective associations of baseline physical behaviours with follow-up QoL, and of changes in behaviours with follow-up QoL using multi-level regression. RESULTS: On average, MVPA decreased by 4.0 min/day/year (SD 8.3) for men and 4.0 min/day/year for women (SD 12.0) between baseline and follow-up. Total sedentary time increased by an average 5.5 min/day/yr (SD 16.0) for men and 6.4 min/day/yr (SD 15.0) for women between baseline and follow-up. Mean (SD) follow-up time was 5.8 (1.8) years. We found that higher baseline MVPA and lower sedentary time was associated with higher subsequent QoL (e.g. 1 h/day greater baseline MVPA was associated with 0.02 higher EQ-5D score, 95% CI 0.06, 0.36). More pronounced declines in activity were associated with worse Hr-QoL (0.005 (95% CI 0.003, 0.008) lower EQ-5D per min/day/yr decrease in MVPA). Increases in sedentary behaviours were also associated with poorer QoL (0.002 lower EQ-5D, 95% CI -0.003, -0.0007 per hour/day/yr increase in total sedentary time). CONCLUSIONS: Promotion of physical activity and limiting sedentary time among older adults may improve quality-of-life, and therefore this relationship ought to be included in future cost effectiveness analyses so that greater commissioning of activity interventions can be considered.

Mortality from angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers in people infected with COVID-19: a cohort study of 3.7 million people.

BACKGROUND: Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first 6 months of the pandemic. METHODS: We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1 January to 21 June 2020) using computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, United Kingdom with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, comorbidities, concurrent medication, smoking status, practice clustering, and household number. RESULTS: There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 1 January 2020 and 21 June 2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.85-1.21 and OR 0.84, 95% CI 0.67-1.07, respectively). CONCLUSION: Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic.

How to embed qualitative research in trials: insights from the feasibility study of the SAFER trial programme.

Qualitative research can enhance the design, conduct and interpretation of trials. Despite this, few trials incorporate qualitative methods, and those that do may not realise their full potential. In this commentary, we highlight how qualitative research can contribute to the design, conduct and day-to-day running of a trial, outlining the working arrangements and relationships that facilitate these contributions. In doing so, we draw on (i) existing frameworks on the role of qualitative research alongside trials and (ii) our experience of integrated qualitative research conducted as part of the feasibility study of the SAFER trial (Screening for Atrial Fibrillation with ECG to Reduce stroke), a cluster randomised controlled trial of screening people aged 70 and above for atrial fibrillation in primary care in England. The activities and presence of the qualitative team contributed to important changes in the design, conduct and day-to-day running of the SAFER feasibility study, and the subsequent main trial, informing diverse decisions concerning trial documentation, trial delivery, timing and content of measures and the information given to participating patients and practices. These included asking practices to give screening results to all participants and not just to 'screen positive' participants, and greater recognition of the contribution of practice reception staff to trial delivery. These changes were facilitated by a 'one research team' approach that underpinned all formal and informal working processes from the outset and maximised the value of both qualitative and trial coordination expertise. The challenging problems facing health services require a combination of research methods and data types. Our experience and the literature show that the benefits of embedding qualitative research in trials are more likely to be realised if attention is given to both structural factors and relationships from the outset. These include sustained and sufficient funding for qualitative research, embedding qualitative research fully within the trial programme, providing shared infrastructure and resources and committing to relationships based on mutual recognition of and respect for the value of different methods and perspectives. We outline key learning for the planning of future trials.Trial registration: Screening for atrial fibrillation with ECG to reduce stroke ISRCTN16939438 (feasibility study); Screening for atrial fibrillation with ECG to reduce stroke - a randomised controlled trial ISRCTN72104369 .

A community jury study exploring the public acceptability of using risk stratification to determine eligibility for cancer screening.

INTRODUCTION: Using risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies. METHODS: We conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40-79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, 'Which approach(es) to inviting people to screening are acceptable, and under what circumstances?' Deliberations and feedback were recorded and analysed using thematic analysis. RESULTS: Across the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high-risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non-modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability. CONCLUSION: Using risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently. PATIENT OR PUBLIC CONTRIBUTION: Two patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co-facilitated the community juries and commented on the interpretation of the findings and final report.

The current state of genetic risk models for the development of kidney cancer: a review and validation.

OBJECTIVE: To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models. METHODS: Risk models were identified from a recent systematic review and the Cancer-PRS web directory. A narrative synthesis of the models, previous validation studies and related genome-wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases, 452; controls, 487 925). RESULTS: A total of 39 genetic models predicting the development of kidney cancer were identified and 31 were validated in the UKB. Several of the genetic-only models (seven of 25) and most of the mixed genetic-phenotypic models (five of six) had some discriminatory ability (area under the receiver operating characteristic curve >0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers. CONCLUSIONS: Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined.

Visualising health risks with medical imaging for changing recipients' health behaviours and risk factors: Systematic review with meta-analysis.

BACKGROUND: There is ongoing clinical and research interest in determining whether providing personalised risk information could motivate risk-reducing health behaviours. We aimed to assess the impact on behaviours and risk factors of feeding back to individuals' images of their bodies generated via medical imaging technologies in assessing their current disease status or risk. METHODS AND FINDINGS: A systematic review with meta-analysis was conducted using Cochrane methods. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to July 28, 2021, with backward and forward citation searches up to July 29, 2021. Eligible studies were randomised controlled trials including adults who underwent medical imaging procedures assessing current health status or risk of disease, for which personal risk may be reduced by modifying behaviour. Trials included an intervention group that received the imaging procedure plus feedback of visualised results and assessed subsequent risk-reducing health behaviour. We examined 12,620 abstracts and included 21 studies, involving 9,248 randomised participants. Studies reported on 10 risk-reducing behaviours, with most data for smoking (8 studies; n = 4,308), medication use (6 studies; n = 4,539), and physical activity (4 studies; n = 1,877). Meta-analysis revealed beneficial effects of feedback of visualised medical imaging results on reduced smoking (risk ratio 1.11, 95% confidence interval [CI] 1.01 to 1.23, p = 0.04), healthier diet (standardised mean difference [SMD] 0.30, 95% CI 0.11 to 0.50, p = 0.003), increased physical activity (SMD 0.11, 95% CI 0.003 to 0.21, p = 0.04), and increased oral hygiene behaviours (SMD 0.35, 95% CI 0.13 to 0.57, p = 0.002). In addition, single studies reported increased skin self-examination and increased foot care. For other behavioural outcomes (medication use, sun protection, tanning booth use, and blood glucose testing) estimates favoured the intervention but were not statistically significant. Regarding secondary risk factor outcomes, there was clear evidence for reduced systolic blood pressure, waist circumference, and improved oral health, and some indication of reduced Framingham risk score. There was no evidence of any adverse effects, including anxiety, depression, or stress, although these were rarely assessed. A key limitation is that there were some concerns about risk of bias for all studies, with evidence for most outcomes being of low certainty. In particular, valid and precise measures of behaviour were rarely used, and there were few instances of preregistered protocols and analysis plans, increasing the likelihood of selective outcome reporting. CONCLUSIONS: In this study, we observed that feedback of medical images to individuals has the potential to motivate risk-reducing behaviours and reduce risk factors. Should this promise be corroborated through further adequately powered trials that better mitigate against risk of bias, such interventions could usefully capitalise upon the widespread and growing use of medical imaging technologies in healthcare.

Why do people take part in atrial fibrillation screening? Qualitative interview study in English primary care.

OBJECTIVES: There is insufficient evidence to support national screening programmes for atrial fibrillation (AF). Nevertheless, some practitioners, policy-makers and special interest groups have encouraged introduction of opportunistic screening in primary care in order to reduce the incidence of stroke through earlier detection and treatment of AF. The attitudes of the public towards AF screening are unknown. We aimed to explore why AF screening participants took part in the screening. DESIGN: Semistructured longitudinal interview study of participant engagement in the SAFER study (Screening for Atrial Fibrillation with ECG to Reduce stroke). We undertook initial interviews face to face, with up to two follow-up telephone interviews during the screening process. We thematically analysed and synthesised these data to understand shared views of screening participation. SETTING: 5 primary care practices in the East of England, UK. PARTICIPANTS: 23 people taking part in the SAFER study first feasibility phase. RESULTS: Participants were supportive of screening for AF, explaining their participation in screening as a 'good thing to do'. Participants suggested screening could facilitate earlier diagnosis, more effective treatment, and a better future outcome, despite most being unfamiliar with AF. Participating in AF screening helped attenuate participants' concerns about stroke and demonstrated their commitment to self-care and being a 'good patient'. Participants felt that the screening test was non-invasive, and they were unlikely to have AF; they therefore considered engaging in AF screening was low risk, with few perceived harms. CONCLUSIONS: Participants assessed the SAFER AF screening programme to be a legitimate, relevant and safe screening opportunity, and complied obediently with what they perceived to be a recommendation to take part. Their unreserved acceptance of screening benefit and lack of awareness of potential harms suggests that uptake would be high but reinforces the importance of ensuring participants receive balanced information about AF screening initiatives. TRIAL REGISTRATION NUMBER: ISRCTN16939438; Pre-results.

"Post-GDM support would be really good for mothers": A qualitative interview study exploring how to support a healthy diet and physical activity after gestational diabetes.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). They are therefore recommended to follow a healthy diet and be physically active in order to reduce that risk. However, achieving and maintaining these behaviours in the postpartum period is challenging. This study sought to explore women's views on suggested practical approaches to achieve and maintain a healthy diet and physical activity to reduce T2DM risk. METHODS: Semi-structured interviews with 20 participants in Cambridgeshire, UK were conducted at three to 48 months after GDM. The participants' current diet and physical activity, intentions for any changes, and views on potential interventions to help manage T2DM risk through these behaviours were discussed. Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions, and thematic framework were based on a recent systematic review. RESULTS: Most of the participants wanted to eat more healthily and be more active. A third of the participants considered that postpartum support for these behaviours would be transformative, a third thought it would be beneficial, and a third did not want additional support. The majority agreed that more information about the impact of diet and physical activity on diabetes risk, support to exercise with others, and advice about eating healthily, exercising with a busy schedule, monitoring progress and sustaining changes would facilitate a healthy diet and physical activity. Four other suggested interventions received mixed responses. It would be acceptable for this support to be delivered throughout pregnancy and postpartum through a range of formats. Clinicians were seen to have important roles in giving or signposting to support. CONCLUSIONS: Many women would appreciate more support to reduce their T2DM risk after GDM and believe that a variety of interventions to integrate changes into their daily lives would help them to sustain healthier lifestyles.

Risk prediction models for symptomatic patients with bladder and kidney cancer: a systematic review.

BACKGROUND: Timely diagnosis of bladder and kidney cancer is key to improving clinical outcomes. Given the challenges of early diagnosis, models incorporating clinical symptoms and signs may be helpful to primary care clinicians when triaging at-risk patients. AIM: To identify and compare published models that use clinical signs and symptoms to predict the risk of undiagnosed prevalent bladder or kidney cancer. DESIGN AND SETTING: Systematic review. METHOD: A search identified primary research reporting or validating models predicting the risk of bladder or kidney cancer in MEDLINE and EMBASE. After screening identified studies for inclusion, data were extracted onto a standardised form. The risk models were classified using TRIPOD guidelines and evaluated using the PROBAST assessment tool. RESULTS: The search identified 20 661 articles. Twenty studies (29 models) were identified through screening. All the models included haematuria (visible, non-visible, or unspecified), and seven included additional signs and symptoms (such as abdominal pain). The models combined clinical features with other factors (including demographic factors and urinary biomarkers) to predict the risk of undiagnosed prevalent cancer. Several models (n = 13) with good discrimination (area under the receiver operating curve >0.8) were identified; however, only eight had been externally validated. All of the studies had either high or unclear risk of bias. CONCLUSION: Models were identified that could be used in primary care to guide referrals, with potential to identify lower-risk patients with visible haematuria and to stratify individuals who present with non-visible haematuria. However, before application in general practice, external validations in appropriate populations are required.

Validation and public health modelling of risk prediction models for kidney cancer using the UK Biobank.

OBJECTIVES: To externally validate risk models for the detection of kidney cancer, as early detection of kidney cancer improves survival and stratifying the population using risk models could enable an individually tailored screening programme. METHODS: We validated the performance of 30 existing phenotypic models predicting the risk of kidney cancer in the UK Biobank cohort (n = 450 687). We compared the discrimination and calibration of models for men, women, and a mixed-sex cohort. Population level data were used to estimate model performance in a screening scenario for a range of risk thresholds (6-year risk: 0.1-1.0%). RESULTS: In all, 10 models had reasonable discrimination (area under the receiver-operating characteristic curve >0.60), although some had poor calibration. Modelling demonstrated similar performance of the best models over a range of thresholds. The models showed an improvement in ability to identify cases compared to age- and sex-based screening. All the models performed less well in women than men. CONCLUSIONS: The present study is the first comprehensive external validation of risk models for kidney cancer. The best-performing models are better at identifying individuals at high risk of kidney cancer than age and sex alone; however, the benefits are relatively small. Feasibility studies are required to determine applicability to a screening programme.

Risk models for recurrence and survival after kidney cancer: a systematic review.

OBJECTIVE: To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. MATERIALS AND METHODS: We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochrane Library from 1 January 2000 to 12 December 2019 to identify studies reporting the performance of one or more prognostic model(s) that predict recurrence-free survival (RFS), cancer-specific survival (CSS) or overall survival (OS) in patients who have undergone surgical resection for localized RCC. For each outcome we summarized the discrimination of each model using the C-statistic and performed multivariate random-effects meta-analysis of the logit transformed C-statistic to rank the models. RESULTS: Of a total of 13 549 articles, 57 included data on the performance of 22 models in external populations. C-statistics ranged from 0.59 to 0.90. Several risk models were assessed in two or more external populations and had similarly high discriminative performance. For RFS, these were the Sorbellini, Karakiewicz, Leibovich and Kattan models, with the UCLA Integrated Staging System model also having similar performance in European/US populations. All had C-statistics ≥0.75 in at least half of the validations. For CSS, they the models with the highest discriminative performance in two or more external validation studies were the Zisman, Stage, Size, Grade and Necrosis (SSIGN), Karakiewicz, Leibovich and Sorbellini models (C-statistic ≥0.80 in at least half of the validations), and for OS they were the Leibovich, Karakiewicz, Sorbellini and SSIGN models. For all outcomes, the models based on clinical features at presentation alone (Cindolo and Yaycioglu) had consistently lower discrimination. Estimates of model calibration were only infrequently included but most underestimated survival. CONCLUSION: Several models had good discriminative ability, with there being no single 'best' model. The choice from these models for each setting should be informed by both the comparative performance and availability of factors included in the models. All would need recalibration if used to provide absolute survival estimates.

'Oh, I've got an appointment': A qualitative interview study exploring how to support attendance at diabetes screening after gestational diabetes.

AIMS: To explore the views of women with a history of gestational diabetes mellitus (GDM) on suggested practical approaches to support diabetes screening attendance after GDM, which is recommended but poorly attended. METHODS: We conducted semi-structured interviews with 20 participants in Cambridgeshire, UK who had been diagnosed with GDM and were 3-48 months postpartum. Interviews covered whether participants had been screened and why, plans for future screening and their views on potential interventions to facilitate attendance (at the first postpartum test and annual testing). Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions and thematic framework were based on a recent systematic review. RESULTS: Sixteen participants had undergone screening since pregnancy, explaining that they had an appointment arranged and wanted reassurance that they did not have diabetes. The participants who had not been tested were not aware that it was recommended. Only 13 had planned to attend subsequent tests at the start of the interview. Eight themes to support future attendance were discussed. The majority of the participants agreed that changing the processes for arranging tests, offering choice in test location and combining appointments would facilitate attendance. Child-friendly clinics, more opportunities to understand GDM and the role of postpartum testing, stopping self-testing and increasing their GP's awareness of their pregnancy received inconsistent feedback. The nature of the test used did not appear to influence attendance. CONCLUSIONS: The participants wanted to be screened for diabetes after GDM. We have identified interventions that could be relatively simply incorporated into routine practice to facilitate screening attendance, such as flexibility in the appointment location or time and sending invitations for tests.

Modification of cardiovascular disease risk by health behaviour change following type 2 diabetes diagnosis.

AIMS: Among adults with type 2 diabetes (T2D), unhealthy behaviours are associated with increased risk of cardiovascular disease (CVD) events. To date, little research has considered whether healthy changes in behaviours following T2D diagnosis reduce CVD risk. METHODS: A cohort of 867 adults with screen-detected T2D, participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial, were followed for 10 years for incidence of CVD events. Diet, alcohol consumption, moderate/vigorous physical activity and smoking were assessed by questionnaire at the time of T2D screening and 1 year later. We estimated associations between health behaviours and CVD using Cox regression. We assessed modification of the associations by behaviour change in the year following T2D diagnosis. RESULTS: Smoking [hazard ratio (HR): 1.73 (95% CI: 1.04, 2.87)] and high fat intake [HR: 1.70 (95% CI: 1.02, 2.85)] were associated with a higher hazard of CVD, while high plasma vitamin C [HR: 0.44 (95% CI: 0.22, 0.87)] and high fibre intake [HR: 0.60 (95% CI: 0.36, 0.99)] were associated with a lower hazard of CVD. Reduction in fat intake following T2D diagnosis modified associations with CVD. In particular, among those with the highest fat intake, decreasing intake attenuated the association with CVD [HR: 0.75 (95% CI: 0.36, 1.56)]. CONCLUSION: Following T2D diagnosis, decreasing fat intake was associated with lower long-term CVD risk. This evidence may raise concerns about low-carbohydrate, high-fat diets to achieve weight loss following T2D diagnosis. Further research considering the sources of fat is needed to inform dietary recommendations. TRIAL REGISTRATION: This trial is registered as ISRCTN86769081. Retrospectively registered on 15 December 2006.

Impact of achievement and change in achievement of lifestyle recommendations in middle-age on risk of the most common potentially preventable cancers.

This study aimed to assess the association between achievement, and within-person change in achievement, of lifestyle recommendations in middle-age and incidence of the most common potentially preventable cancers. We used data from 44,572 participants from the Swedish Västerbotten Intervention Programme who had attended at least two health checks 9-11 years apart. We assessed the association between the mean number of healthy lifestyle recommendations achieved (lifestyle score), and change in lifestyle score between the health checks, and risk of one or more of the eight most common potentially preventable cancers using Cox regression. Participants were followed-up for 11.0 (SD 4.9) years. A higher mean lifestyle score was associated with a lower hazard of cancer in men (HR 0.81 (95%CI 0.74-0.90) per unit increase) and women (HR 0.90 (0.84-0.96)). There was no evidence of a linear association between change in lifestyle score and risk (HR 0.93 (0.85-1.03) and HR 1.004 (0.94-1.07) per unit change for men and women respectively). When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54-1.00) and 1.02 (0.84-1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective.