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.

Factors Influencing Recovery From Pediatric Stroke Based on Discussions From a UK-Based Online Stroke Community: Qualitative Thematic Study.

BACKGROUND: The incidence of stroke in children is low, and pediatric stroke rehabilitation services are less developed than adult ones. Survivors of pediatric stroke have a long poststroke life expectancy and therefore have the potential to experience impairments from their stroke for many years. However, there are relatively few studies characterizing these impairments and what factors facilitate or counteract recovery. OBJECTIVE: This study aims to characterize the main barriers to and facilitators of recovery from pediatric stroke. A secondary aim was to explore whether these factors last into adulthood, whether they change, or if new factors impacting recovery emerge in adulthood. METHODS: We performed a qualitative thematic analysis based on posts from a population of participants from a UK-based online stroke community, active between 2004 and 2011. The analysis focused on users who talked about their experiences with pediatric stroke, as identified by a previous study. The posts were read by 3 authors, and factors influencing recovery from pediatric stroke were mapped into 4 areas: medical, physical, emotional, and social. Factors influencing recovery were divided into short-term and long-term factors. RESULTS: There were 425 posts relating to 52 survivors of pediatric stroke. Some survivors of stroke posted for themselves, while others were talked about by a third party (mostly parents; 31/35, 89% mothers). In total, 79% (41/52) of survivors of stroke were aged ≤18 years and 21% (11/52) were aged >18 years at the time of posting. Medical factors included comorbidities as a barrier to recovery. Medical interventions, such as speech and language therapy and physiotherapy, were also deemed useful. Exercise, particularly swimming, was deemed a facilitator. Among physical factors, fatigue and chronic pain could persist decades after a stroke, with both reported as a barrier to feeling fully recovered. Tiredness could worsen existing stroke-related impairments. Other long-standing impairments were memory loss, confusion, and dizziness. Among emotional factors, fear and uncertainty were short-term barriers, while positivity was a major facilitator in both short- and long-term recovery. Anxiety, grief, and behavioral problems hindered recovery. The social barriers were loneliness, exclusion, and hidden disabilities not being acknowledged by third parties. A good support network and third-party support facilitated recovery. Educational services were important in reintegrating survivors into society. Participants reported that worrying about losing financial support, such as disability allowances, and difficulties in obtaining travel insurance and driving licenses impacted recovery. CONCLUSIONS: The lived experience of survivors of pediatric stroke includes long-term hidden disabilities and barriers to rehabilitation. These are present in different settings, such as health care, schools, workplaces, and driving centers. Greater awareness of these issues by relevant professional groups may help ameliorate them.

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.

Progression of stroke risk in patients aged <65 years diagnosed with atrial fibrillation: a cohort study in general practice.

BACKGROUND: As a result of new technologies, atrial fibrillation (AF) is more likely to be diagnosed in people aged <65 years. AIM: To investigate the risk of someone diagnosed with AF aged <65 years developing an indication for anticoagulation before they reach 65 years. DESIGN AND SETTING: Population-based cohort study of patients from English practices using the Clinical Practice Research Datalink, a primary care database of electronic medical records. METHOD: The study included patients aged <65 years newly diagnosed with AF. The CHA2DS2-VASc score was derived at time of diagnosis based on patients' medical records. Patients not eligible for anticoagulation were followed up until they became eligible or turned 65 years old. The primary outcome of interest was development of a risk factor for stroke in AF. RESULTS: Among 18 178 patients aged <65 years diagnosed with AF, 9188 (50.5%) were eligible for anticoagulation at the time of diagnosis. Among the 8990 patients not eligible for anticoagulation, 1688 (18.8%) developed a risk factor during follow-up before reaching 65 years of age or leaving the cohort for other reasons, at a rate of 6.1 per 100 patient-years. Hypertension and heart failure were the most common risk factors to occur, with rates of 2.65 (95% CI = 2.47 to 2.84) and 1.58 (95% CI = 1.45 to 1.72) per 100 patient-years, respectively. The rate of new diabetes was 0.95 (95% CI = 0.85 to 1.06) per 100 patient-years. CONCLUSION: People aged <65 years with AF are at higher risk of developing hypertension, heart failure, and diabetes than the general population, so may warrant regular review to identify new occurrence of such risk factors.

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol.

INTRODUCTION: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a 'survey leading to a trial' design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. METHODS AND ANALYSIS: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. ETHICS AND DISSEMINATION: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05829265.

Why do people choose not to take part in screening? Qualitative interview study of atrial fibrillation screening nonparticipation.

INTRODUCTION: While screening uptake is variable, many individuals feel they 'ought' to participate in screening programmes to aid the detection of conditions amenable to early treatment. Those not taking part in screening are often presented as either hindered by practical or social barriers or personally at fault. Why some people choose not to participate receives less consideration. METHODS: We explored screening nonparticipation by examining the accounts of participants who chose not to participate in screening offered by a national research trial of atrial fibrillation (AF) screening in England (SAFER: Screening for Atrial Fibrillation with ECG to Reduce stroke). AF is a heart arrhythmia that increases in prevalence with age and increases the risk of stroke. Systematic screening for AF is not a nationally adopted programme within the United Kingdom; it provides a unique opportunity to explore screening nonparticipation outside of the norms and values attached to existing population-based screening programmes. We interviewed people aged over 65 (n = 50) who declined an invitation from SAFER and analysed their accounts thematically. RESULTS: Beyond practical reasons for nonparticipation, interviewees challenged the utility of identifying and managing AF earlier. Many questioned the benefits of screening at their age. The trial's presentation of the screening as research made it feel voluntary-something they could legitimately decline. CONCLUSION: Nonparticipants were not resistant to engaging in health-promoting behaviours, uninformed about screening or unsupportive of its potential benefits. Instead, their consideration of the perceived necessity, legitimacy and utility of this screening shaped their decision not to take part. PATIENT OR PUBLIC CONTRIBUTION: The SAFER programme is guided by four patient and carer representatives. The representatives are embedded within the team (e.g., one is a co-applicant, another sits on the programme steering committee) and by participating in regular meetings advise on all aspects of the design, management and delivery of the programme, including engaging with interpreting and disseminating the findings. For the qualitative workstream, we established a supplementary patient and public involvement group with whom we regularly consult about research design questions.

An artificial intelligence-based model for prediction of atrial fibrillation from single-lead sinus rhythm electrocardiograms facilitating screening.

AIMS: Screening for atrial fibrillation (AF) is recommended in the European Society of Cardiology guidelines. Yields of detection can be low due to the paroxysmal nature of the disease. Prolonged heart rhythm monitoring might be needed to increase yield but can be cumbersome and expensive. The aim of this study was to observe the accuracy of an artificial intelligence (AI)-based network to predict paroxysmal AF from a normal sinus rhythm single-lead ECG. METHODS AND RESULTS: A convolutional neural network model was trained and evaluated using data from three AF screening studies. A total of 478 963 single-lead ECGs from 14 831 patients aged ≥65 years were included in the analysis. The training set included ECGs from 80% of participants in SAFER and STROKESTOP II. The remaining ECGs from 20% of participants in SAFER and STROKESTOP II together with all participants in STROKESTOP I were included in the test set. The accuracy was estimated using the area under the receiver operating characteristic curve (AUC). From a single timepoint ECG, the artificial intelligence-based algorithm predicted paroxysmal AF in the SAFER study with an AUC of 0.80 [confidence interval (CI) 0.78-0.83], which had a wide age range of 65-90+ years. Performance was lower in the age-homogenous groups in STROKESTOP I and STROKESTOP II (age range: 75-76 years), with AUCs of 0.62 (CI 0.61-0.64) and 0.62 (CI 0.58-0.65), respectively. CONCLUSION: An artificial intelligence-enabled network has the ability to predict AF from a sinus rhythm single-lead ECG. Performance improves with a wider age distribution.

What are the outcomes of dietary interventions in Heart Failure with preserved Ejection Fraction? A systematic review and meta-analysis.

AIMS: To determine the efficacy of dietary interventions in Heart Failure with preserved Ejection Fraction (HFpEF). METHOD AND RESULTS: Keyword searches were performed in five bibliographic databases to identify randomized or controlled studies of dietary interventions conducted in HFpEF or mixed heart failure (HF) samples published in the English language. Studies were appraised for bias and synthesized into seven categories based on the similarity of the intervention or targeted population. The quality of the body of evidence was assessed via the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. Twenty-five unique interventions were identified; 17 were considered for meta-analysis. Most studies were judged to be at high risk of bias. There was moderate-quality evidence that caloric restriction led to clinically meaningful improvements in blood pressure and body weight. There was moderate-quality evidence that carbohydrate restriction resulted in meaningful reductions in blood pressure. There was very low-quality evidence that protein supplementation improved blood pressure and body weight and moderate-quality evidence for clinically meaningful improvements in function. CONCLUSIONS: While some types of dietary interventions appeared to deliver clinically meaningful change in critical outcomes; the study heterogeneity and overall quality of the evidence make it difficult to make firm recommendations. Greater transparency when reporting the nutritional composition of interventions would enhance the ability to pool studies. REGISTRATION: PROSPERO CRD42019145388.

What dietary interventions have been tested in heart failure with preserved ejection fraction? A systematic scoping review.

AIMS: To determine what dietary interventions have been tested in heart failure with preserved ejection fraction (HFpEF), the modulation method, and outcomes employed and to summarize any evidence for benefit. METHODS AND RESULTS: We performed key word searches in five bibliographic databases from 2001 to 2021, to identify randomized or experimental dietary interventions tested in HFpEF or mixed heart failure (HF) samples. Study characteristics were summarized according to population, intervention, comparator, outcome categories and intervention complexity was assessed. Twenty-five clinical investigations were retrieved; only 10 (40%) were conducted exclusively in HFpEF; the remainder enrolled mixed HF samples. Most studies employed either highly tailored prescribed diets (n = 12, 48%) or dietary supplementation (n = 10, 40%) modalities. Dietary pattern interventions (n = 3, 12%) are less well represented in the literature. CONCLUSION: Heterogeneity made pooling studies challenging. Better reporting of baseline characteristics and the use of standardized HF lexicon would ensure greater confidence in interpretation of studies involving mixed HF populations. The field would benefit greatly from explicit reporting of the biological mechanism of action (e.g. the causal pathway) that an intervention is designed to modulate so that studies can be synthesized via their underlying mechanism of action by which diet may affect HF. An extension of the current set of core outcomes proposed by the European Society of Cardiology Heart Failure Association would ensure dietary clinical endpoints are more consistently defined and measured. REGISTRATION: PROSPERO: CRD42019145388.

The development of a self-management intervention for stroke survivors - My Life After Stroke (MLAS).

PURPOSE: Long-term needs of stroke survivors (especially psychosocial needs and stroke prevention) are not adequately addressed. Self-management programmes exist but the optimal content and delivery approach is unclear. We aim to describe the process undertook to develop a structured self-management programme to address these unmet needs. MATERIALS AND METHODS: Based on the Medical Research Council framework for complex interventions, the development involved three phases: "Exploring the idea": Evidence synthesis and patient and public involvement (PPI) with stroke survivors, carers and healthcare professionals. "The iterative phase": Development and iterative refinement of the format, content, underpinning theories and philosophy of the self-management programme My Life After Stroke (MLAS), with PPI. MLAS consists of two individual appointments and four group sessions over nine weeks, delivered interactively by two trained facilitators. It aims to build independence, confidence and hope and focusses on stroke prevention, maximising physical potential, social support and managing emotional responses. MLAS is grounded in the narrative approach and social learning theory. "Ready for research": The refinement of a facilitator curriculum and participant resources to support programme delivery. RESULTS: Through a systematic process, we developed an evidence- and theory-based self-management programme for stroke survivors. CONCLUSIONS: MLAS warrants evaluation in a feasibility study.Implications for rehabilitationMy Life After Stroke(MLAS) has been developed using a systematic process, to address the unmet needs of stroke survivors.This systematic process, involved utilising evidence, theories, patient and public involvement, expertise and guidelines from other long-term conditions. This may further help the development of similar self-management programme within the field of stroke.MLAS warrants further evaluation within a feasibility study.

Cumulative complexity: a qualitative analysis of patients' experiences of living with heart failure with preserved ejection fraction.

AIMS: To investigate how heart failure with preserved ejection fraction (HFpEF), within the context of limited clinical services, impacts patients' lives. METHODS AND RESULTS: Secondary thematic analysis informed by the cumulative complexity model (CCM), of interview transcripts from 77 people diagnosed with HFpEF and their carers. Four themes corresponding to the core concepts of workload, capacity, access, and outcome described in the CCM were generated. Theme 1: Shouldering a heavy workload described the many tasks expected of people living with HFpEF. Theme 2: The multiple threats to capacity described how patients and carers strived to engage with this work, but were often faced with multiple threats such as symptoms and mobility limitations. Deficient illness identity (Theme 3) reflects how HFpEF either was not recognized or was perceived as a more benign form of HF and therefore afforded less importance or priority. These themes contributed to a range of negative physical, social, and psychological outcomes and the perception of loss of control described in Theme 4: Spiraling complexity. CONCLUSIONS: The constellation of HFpEF, multi-morbidity, and ageing creates many demands that people with HFpEF are expected to manage. Concurrently, the same syndromes threaten their ability to physically enact this work. Patients' recollections of their interactions with health professionals suggest that there is a widespread misunderstanding of HFpEF, which can prohibit access to care that could potentially reduce or prevent deterioration.

Patients' experience of and participation in a stroke self-management programme, My Life After Stroke (MLAS): a multimethod study.

OBJECTIVE: A self-management programme, My Life After Stroke (MLAS), was developed to support stroke survivors. This evaluation reports patients' experience. DESIGN: Multimethod, involving interviews and questionnaires. SETTING: 23 general practices in the intervention arm of a cluster randomised controlled trial in East of England and East Midlands, UK. PARTICIPANTS: People on the stroke registers of participating general practices were invited to attend an MLAS programme. INTERVENTIONS: MLAS comprises one-to-one and group-based sessions to promote independence, confidence and hope. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was uptake of the programme. Participants who declined MLAS were sent a questionnaire to ascertain why. Attendees of four programmes completed evaluation forms. Attendees and non-attendees of MLAS were interviewed. Ad-hoc email conversations with the lead author were reviewed. Thematic analysis was used for qualitative data. RESULTS: 141/420 (34%) participants (mean age 71) attended an MLAS programme and 103 (73%) completed 1. 64/228 (28%) participants who declined MLAS gave reasons as: good recovery, ongoing health issues, logistical issues and inappropriate. Nearly all attendees who completed questionnaires felt that process criteria such as talking about their stroke and outcomes such as developing a strong understanding of stroke had been achieved. CONCLUSIONS: MLAS was a positive experience for participants but many stroke survivors did not feel it was appropriate for them. Participation in self-management programmes after stroke might be improved by offering them sooner after the stroke and providing a range of delivery options beyond group-based, face-to-face learning. TRIAL REGISTRATION NUMBER: NCT03353519, NIH.

Prioritising electrocardiograms for manual review to improve the efficiency of atrial fibrillation screening.

Screening for atrial fibrillation (AF) could reduce the incidence of stroke by identifying undiagnosed AF and prompting anticoagulation. However, screening may involve recording many electrocardiograms (ECGs) from each participant, several of which require manual review which is costly and time-consuming. The aim of this study was to investigate whether the number of ECG reviews could be reduced by using a model to prioritise ECGs for review, whilst still accurately diagnosing AF. A multiple logistic regression model was created to estimate the likelihood of an ECG exhibiting AF based on the mean RR-interval and variability in RR-intervals. It was trained on 1,428 manually labelled ECGs from 144 AF screening programme participants, and evaluated using 11,443 ECGs from 1,521 participants. When using the model to order ECGs for review, the number of reviews for AF participants was reduced by 74% since no further reviews are required after an AF ECG is identified; however, it did not impact the number of reviews in non-AF participants (the vast majority of participants), so the overall number of reviews was reduced by 3% with no missed AF diagnoses. When using the model to also exclude ECGs from review, the overall number of reviews was reduced by 28% with no missed AF diagnoses, and by 53% with only 4% of AF diagnoses missed. In conclusion, the workload can be reduced by using a model to prioritise ECGs for review. Ordering ECGs alone only provides only a moderate reduction in workload. The additional use of a threshold to exclude ECGs from review provides a much greater reduction in workload at the expense of some missed AF diagnoses. Clinical Relevance-This shows the potential benefit of using a model to prioritise electrocardiograms for review in order to reduce the manual workload of AF screening.

Detecting beats in the photoplethysmogram: benchmarking open-source algorithms.

The photoplethysmogram (PPG) signal is widely used in pulse oximeters and smartwatches. A fundamental step in analysing the PPG is the detection of heartbeats. Several PPG beat detection algorithms have been proposed, although it is not clear which performs best.Objective:This study aimed to: (i) develop a framework with which to design and test PPG beat detectors; (ii) assess the performance of PPG beat detectors in different use cases; and (iii) investigate how their performance is affected by patient demographics and physiology.Approach:Fifteen beat detectors were assessed against electrocardiogram-derived heartbeats using data from eight datasets. Performance was assessed using theF1score, which combines sensitivity and positive predictive value.Main results:Eight beat detectors performed well in the absence of movement withF1scores of ≥90% on hospital data and wearable data collected at rest. Their performance was poorer during exercise withF1scores of 55%-91%; poorer in neonates than adults withF1scores of 84%-96% in neonates compared to 98%-99% in adults; and poorer in atrial fibrillation (AF) withF1scores of 92%-97% in AF compared to 99%-100% in normal sinus rhythm.Significance:Two PPG beat detectors denoted 'MSPTD' and 'qppg' performed best, with complementary performance characteristics. This evidence can be used to inform the choice of PPG beat detector algorithm. The algorithms, datasets, and assessment framework are freely available.

Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.

INTRODUCTION: People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention. METHODS AND ANALYSIS: This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff. ETHICS AND DISSEMINATION: Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media. TRIAL REGISTRATION NUMBER: ISRCTN39864003.

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 .

Cost-Effectiveness of Antihypertensive Deprescribing in Primary Care: a Markov Modelling Study Using Data From the OPTiMISE Trial.

BACKGROUND: Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach. METHODS: A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon. Model population characteristics were estimated using data from the OPTiMISE antihypertensive deprescribing trial, and the effects of blood pressure changes on outcomes were derived from the literature. Health-related quality of life was modeled in Quality-Adjusted Life Years (QALYs) and presented as costs per QALY gained. RESULTS: In the base-case analysis, medication reduction resulted in lower costs than usual care (mean difference £185), but also lower QALYs (mean difference 0.062) per patient over a life-time horizon. Usual care was cost-effective at £2975 per QALY gained (more costly, but more effective). Medication reduction resulted more heart failure and stroke/TIA events but fewer adverse events. Medication reduction may be the preferred strategy at a willingness-to-pay of £20 000/QALY, where the baseline absolute risk of serious drug-related adverse events was ≥7.7% a year (compared with 1.7% in the base-case). CONCLUSIONS: Although there was uncertainty around many of the assumptions underpinning this model, these findings suggest that antihypertensive medication reduction should not be attempted in many older patients with controlled systolic blood pressure. For populations at high risk of adverse effects, deprescribing may be beneficial, but a targeted approach would be required in routine practice.

Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis.

Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation vs. no initiation) and per-protocol (PP, sustained statin use vs. no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64-0.75) in ITT analysis and 0.55 (95% CI 0.50-0.62) in PP analysis. The corresponding aHRITT and aHRPP were 0.87 (95% CI 0.79-0.95) and 0.70 (95% CI 0.62-0.80) for CHD, 1.03 (95% CI 0.82-1.29) and 1.09 (95% CI 0.77-1.54) for peptic ulcer, and 0.88 (95% CI 0.80-0.96) and 0.86 (95% CI 0.75-0.98) for fracture. Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time. The observed association of statin use with post-stroke dementia may in part be overestimated due to unmeasured confounding shared with the association between statin use and fracture.

Wearable Photoplethysmography for Cardiovascular Monitoring.

Smart wearables provide an opportunity to monitor health in daily life and are emerging as potential tools for detecting cardiovascular disease (CVD). Wearables such as fitness bands and smartwatches routinely monitor the photoplethysmogram signal, an optical measure of the arterial pulse wave that is strongly influenced by the heart and blood vessels. In this survey, we summarize the fundamentals of wearable photoplethysmography and its analysis, identify its potential clinical applications, and outline pressing directions for future research in order to realize its full potential for tackling CVD.