Women's experiences of over-the-counter and prescription medication during pregnancy in the UK: findings from survey free-text responses and narrative interviews.

OBJECTIVES: To explore women's experiences of over-the-counter and prescription medication advice and use during pregnancy. DESIGN: A study design consisting of an online survey and nested in-depth interviews with a subsample of participants. We analysed data from survey free-text responses and in-depth interviews using thematic analysis. Quantitative survey data is published elsewhere. SETTING: The UK. PARTICIPANTS: Women were eligible if living in the UK, aged 16-45 years, were pregnant or had been pregnant in the last 5 years regardless of pregnancy outcome. A total of 7090 women completed the survey, and 34 women who collectively had experienced 68 pregnancies were subsequently interviewed. RESULTS: Medication prescribing and use during pregnancy was common. The prescribing, dispensing and taking of some advised medications were restricted through women's or prescribers' fear of fetal harm. Lack of adherence to national prescribing guidance, conflicting professional opinion and poor communication resulted in maternal anxiety, avoidable morbidity and women negotiating complex and distressing pathways to obtain recommended medications. In contrast, some women felt overmedicated and that pharmacological treatments were used without exploring other options first. CONCLUSION: Increased translation of national guidance into practice and greater personalisation of antenatal care are needed to improve the safety, efficacy and personalisation of prescribing in pregnancy.

Home-based cardiac rehabilitation for people with heart failure and their caregivers: a mixed-methods analysis of the roll out an evidence-based programme in Scotland (SCOT:REACH-HF study).

AIMS: Alternative models of cardiac rehabilitation (CR) are required to improve CR access and uptake. Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) is a comprehensive home-based rehabilitation and self-management programme, facilitated by trained health professionals, for people with heart failure (HF) and their caregivers. REACH-HF was shown to be clinically effective and cost-effective in a multi-centre randomized trial. The SCOT:REACH-HF study assessed implementation of REACH-HF in routine clinical practice in NHS Scotland. METHODS AND RESULTS: A mixed-method implementation study was conducted across six regional Health Boards. Of 136 people with HF and 56 caregivers recruited, 101 people with HF and 26 caregivers provided 4-month follow-up data, after participating in the 12-week programme. Compared with baseline, REACH-HF participation resulted in substantial gains in the primary outcome of health-related quality of life, as assessed by the Minnesota Living with Heart Failure Questionnaire (mean difference: -9.8, 95% CI: -13.2 to -6.4, P < 0.001). Improvements were also seen in secondary outcomes (PROM-CR+; EQ-5D-5L; Self-Care of Heart Failure Index (SCHFI) domains of maintenance and symptom perception; Caregiver Contribution to Self-Care domains of symptom perception and management). Twenty qualitative interviews were conducted with 11 REACH-HF facilitators, five supporting clinicians, and four national stakeholders. Interviewees were largely positive about REACH-HF, considering it to have 'filled a gap' where centre-based CR was not an option. Key issues to support future roll-out were also identified. CONCLUSION: Our findings support wider roll-out of REACH-HF as an alternative to centre-based models, to improve CR access and uptake for people with HF.

WRISK voices: A mixed-methods study of women's experiences of pregnancy-related public health advice and risk messages in the UK.

BACKGROUND: Women receive many public health messages relating to pregnancy which are intended to improve outcomes for babies and mothers. However, negotiating the risk landscape and maternity care system can feel confusing and disempowering. Relationships between women and their healthcare providers are paramount, but they can be adversely affected by issues of trust and autonomy. METHODS: We used a nested study design including an online survey and qualitative interviews to gain an understanding of women's experiences of risk messages during pregnancy. We purposively sampled survey participants to ensure the interview population included women whose voices are seldom heard and are disproportionately impacted by poor risk communication. RESULTS: A total of 7,009 women responded to the survey, and 34 women participated in interviews. Participants received public health and risk messages from a range of sources. Data showed that women wanted a balance between a "better safe than sorry" approach and evidence-based information and advice. Women reported a discrepancy between the topics they received a lot of information on and areas in which they felt they needed more advice. Many participants said they were given conflicting advice, and the way information was delivered sometimes challenged their autonomy. We identified that younger women (<20 years old) and women with higher BMIs experienced stigmatisation in their maternity care. CONCLUSIONS: Our research shows the importance of risk communication that respects women's autonomy and trusts them to make decisions about their own pregnancy. We identified a need for a layered approach to risk communication. Whilst some women are happy to adopt precautionary behaviour without discussion, others will want a thorough examination of the evidence-base. Our findings suggest that more individualised care, continuity, and less judgement and stigmatisation from HCPs will improve experiences for women and may lead to better engagement with services.

Risk messages relating to fertility and pregnancy: a media content analysis.

Background: The UK print and online media is an important channel by which scientific research is communicated to the public. Media risk messages relating to pregnancy or fertility contribute to the context of reproductive decision making, but their fidelity to the underlying science has been questioned. Method: We measured the volume, distribution and content of science-based risk headlines relating to pregnancy or fertility in the UK media over four months. We grouped headlines into unique stories and categorised them by exposure and outcome of interest. We selected four unique stories for closer content analysis and assessed their fidelity to the underlying science, with attention to the role of press releases. Results: We identified 171 headlines over four months (average 43 per month), comprising 56 unique stories. The unique stories most commonly concerned maternal risk factors (n=46) and child health outcomes (n=46). Maternal health outcomes were less frequently the focus (n=20). The most common risk factors in the media coverage were maternal food and drink (n=15), maternal medication and medical interventions (n=9), and maternal health factors (n=6). Media reports were largely faithful to press releases. Where substantive deviations from the underlying scientific study were identified, these could mostly be traced back to press releases or quotes from the study's authors. Press releases often omitted caveats which were reinstated at the media reporting stage, alongside additional expert criticism. Conclusions: Frequent science-based risk messages in the UK media frame mothers as vectors of potential harm to children, who are the focus of health outcomes. Largely, the media does not introduce misinformation, but reports press releases faithfully with additional caveats and expert commentary. Press releases fulfil an interpretative role, often omitting caveats and introducing new elements and advice to women. Their role as a bridge between scientific and lay audiences is discussed.

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. Design, Setting, and Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. Main Outcomes and Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). Conclusions and Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

The impact of COVID-19 on the management of heart failure: a United Kingdom patient questionnaire study.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic has created significant challenges to healthcare globally, necessitating rapid restructuring of service provision. This questionnaire survey was conducted amongst adult heart failure (HF) patients in the United Kingdom (UK), to understand the impact of COVID-19 upon HF services. METHODS AND RESULTS: The survey was conducted by the Pumping Marvellous Foundation, a UK HF patient charity. 'Survey Monkey' was used to disseminate the questionnaire in the Pumping Marvellous Foundation 's online patient group and in 10 UK hospitals (outpatient hospital and community HF clinics). There were 1050 responses collected (693/1050-66% women); 55% (579/1050) were aged over 60 years. Anxiety level was significantly higher regarding COVID-19 (mean 7 ± 2.5 on anxiety scale of 0 to 10) compared with anxiety regarding HF (6.1 ± 2.4; P < 0.001). Anxiety was higher amongst patients aged ≤60 years about HF (6.3 ± 2.2 vs. 5.9 ± 2.5 in those aged >60 years; P = 0.005) and COVID-19 (7.3 ± 2.3 vs. 6.7 ± 2.6 those aged >60 years; P < 0.001). Sixty-five per cent of respondents (686/1050) reported disruption to HF appointments (cancellation or postponement) during the lockdown period. Thirty-seven per cent reported disruption to medication prescription services, and Thirty-four per cent reported inability to access their HF teams promptly. Thirty-two per cent expressed reluctance to attend hospital (25% stated they would only attend hospital if there was no alternative, and 7% stated that they would not attend hospital at all). CONCLUSIONS: The COVID-19 pandemic has caused significant anxiety amongst HF patients regarding COVID-19 and HF. Cancellation or postponement of scheduled clinic appointments, investigations, procedures, prescription, and monitoring services were implicated as sources of anxiety.

Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF).

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. METHODS: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide). RESULTS: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, -10.8 to -1.2) mL/m2 (P=0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, -13.7 to -2.6) mL/m2 (P=0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%-47%), P=0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. CONCLUSIONS: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03485092.

Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated. OBJECTIVES: This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na+ excess. METHODS: Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na+, and K+) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation). RESULTS: Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 4.66 [IQR: 3.70 to 6.15] µl × 100 ml of tissue-1 × min-1 × mm Hg-1; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 5.66 [IQR: 4.69 to 8.38] µl × 100 ml of tissue-1 × min-1 × mm Hg-1; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na+ excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001). CONCLUSIONS: Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.

Protocol for an implementation study of an evidence-based home cardiac rehabilitation programme for people with heart failure and their caregivers in Scotland (SCOT:REACH-HF).

INTRODUCTION: Despite evidence that cardiac rehabilitation (CR) is an essential component of care for people with heart failure, uptake is low. A centre-based format is a known barrier, suggesting that home-based programmes might improve accessibility. The aim of SCOT: Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) is to assess the implementation of the REACH-HF home-based CR intervention in the context of the National Health Service (NHS) in Scotland.This paper presents the design and protocol for this observational implementation study. Specific objectives of SCOT:REACH-HF are to: (1) assess service-level facilitators and barriers to the implementation of REACH-HF; (2) compare real-world patient and caregiver outcomes to those seen in a prior clinical trial; and (3) estimate the economic (health and social) impact of implementing REACH-HF in Scotland. METHODS AND ANALYSIS: The REACH-HF intervention will be delivered in partnership with four 'Beacon sites' across six NHS Scotland Health Boards, covering rural and urban areas. Health professionals from each site will be trained to facilitate delivery of the 12-week programme to 140 people with heart failure and their caregivers. Patient and caregiver outcomes will be assessed at baseline and 4-month follow-up. Assessments include the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-dimension EuroQol 5L, Hospital Anxiety and Depression Scale, and the Caregiver Burden Questionnaire. Qualitative interviews will be conducted with up to 20 health professionals involved in programme delivery (eg, cardiac nurses, physiotherapists). 65 facilitator-patient consultations will be audio recorded and assessed for fidelity. Integrative analysis will address key research questions on fidelity, context and CR participant-related outcomes. The SCOT:REACH-HF findings will inform the future potential roll-out of REACH-HF in Scotland. ETHICS AND DISSEMINATION: The study has been given ethical approval by the West of Scotland Research Ethics Service (reference 20/WS/0038, approved 25 March 2020). Written informed consent will be obtained from all participants. The study is listed on the ISRCTN registry with study ID ISRCTN53784122. The research team will ensure that the study is conducted in accordance with both General Data Protection Regulations and the University of Glasgow's Research Governance Framework. Findings will be reported to the funder and shared with Beacon Sites, to facilitate service evaluation, planning and good practice. To broaden interest in, and understanding of REACH-HF, we will seek to publish in peer-reviewed scientific journals and present at stakeholder events, national and international conferences.

Unlocking the potential for digital mental health technologies in the UK: a Delphi exercise.

BACKGROUND: Digitally enabled services can contribute to the support, treatment and prevention of mental health difficulties; however, questions remain regarding how we can most usefully harness such technology in primary and secondary mental healthcare settings. AIMS: To identify barriers and facilitators to enable the potential of digital mental health in England, Scotland, Wales and Northern Ireland. METHOD: A three-round Delphi exercise was carried out online with 16 participants from across the four nations of the UK representing the following stakeholder groups: service providers, health professionals, policymakers, lived experience, small and medium enterprises and academics. Qualitative data were collected in the first round (80 fragments) that were then coded to produce a 26-item round-two questionnaire for participant rating. Participants were given the opportunity to reconsider their scores in light of the group responses in round three. RESULTS: Eight statements under the following five themes reached consensus with median scores between 8 and 10 (i.e. important/very important): co-production; the human element; data security; funding; and regulation. CONCLUSIONS: The Delphi process allowed consensus to be achieved regarding the factors that experts consider important for harnessing technology in primary and secondary mental healthcare. Knowledge of these factors can help users and providers of mental health services negotiate how best to move forward with digitally enabled systems of care.

Improving medication optimisation in left ventricular systolic dysfunction after acute myocardial infarction.

Glasgow city has the highest cardiovascular disease (CVD) mortality rate in the UK. Patients with left ventricular systolic dysfunction after acute myocardial infarction represent a 'high-risk' cohort for adverse CVD outcomes. The optimisation of secondary prevention medication in this group is often suboptimal. Our aim was to improve the use and target dosing of ACE inhibitors (ACEI), angiotensin II receptor blockers (ARBs) and beta-blockers in such patients, through pharmacist-led clinics and cardiology multidisciplinary team collaboration. Retrospective audits characterised baseline care. Prospective pharmacist-led clinics were piloted and rolled out across seven hospitals and primary care localities over four Plan-Do-Study-Act cycles. 'Hub' and 'spoke' clinics utilised independent prescribing pharmacists with different levels of cardiology experience. Pharmacists were trained through a bespoke training programme-'Teach and Treat'. Consultant cardiologists provided senior support and governance. Patients attending prospective pharmacist-led clinics were more likely to be prescribed an ACEI (or ARB) and beta-blocker (n=856/885 (97%) vs n=233/255 (91%), p<0.001 and n=813/885 (92%) vs n=224/255 (88%), p=0.048, respectively) and be on target dose of ACEI (or ARB) and beta-blocker (n=585/885 (66%) vs n=64/255 (25%), p<0.001 and n=218/885 (25%) vs n=17/255 (7%), p<0.001, respectively) compared with baseline. The mean dose of ACEI (or ARB) and beta-blocker was also higher (79% vs 48% of target dose, p<0.001% and 48% vs 33% of target dose, p<0.001, respectively) compared with baseline. Use of secondary prevention medication was significantly improved by pharmacist and cardiology collaboration. These improvements were sustained across a 4-year period, supported by a novel approach called 'Teach and Treat' which linked training to defined clinical service delivery. Further work is needed to assess the impact of the programme on long-term CVD outcomes.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS).

INTRODUCTION: There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. METHODS AND ANALYSIS: 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. TRIAL REGISTRATION NUMBER: NCT01895751 (ClinicalTrials.gov).

Selective small molecule targeting ß-catenin function discovered by in vivo chemical genetic screen.

The canonical Wnt signaling pathway, mediated by the transcription factor ß-catenin, plays critical roles in embryonic development and represents an important therapeutic target. In a zebrafish-based in vivo screen for small molecules that specifically perturb embryonic dorsoventral patterning, we discovered a compound named windorphen that selectively blocks the Wnt signal required for ventral development. Windorphen exhibits remarkable specificity toward ß-catenin-1 function, indicating that the two ß-catenin isoforms found in zebrafish are not functionally redundant. We show that windorphen is a selective inhibitor of p300 histone acetyltransferase, a coactivator that associates with ß-catenin. Finally, windorphen robustly and selectively kills cancer cells that harbor Wnt-activating mutations, supporting the therapeutic potential of this Wnt inhibitor class.

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Assessment of commonly available education materials in heart failure clinics.

BACKGROUND: Health literacy (HL) is an established independent predictor of cardiovascular outcomes. Approximately 90 million Americans have limited HL and read at the fifth grade level or lower. Therefore, we sought to determine the suitability and readability level of common cardiovascular patient education materials (PEM) related to heart failure and heart-healthy lifestyle. METHODS AND RESULTS: The suitability and readability of written PEMs were assessed using the suitability assessment of materials (SAM) and Fry readability formula. The SAM criteria are composed of the following categories: message content, text appearance, visuals, and layout and design. We obtained a convenience sample of 18 English-written cardiovascular PEMs freely available from major health organizations. Two reviewers independently appraised the PEMs. Final suitability scores ranged from 12% to 87%. Readability levels ranged between 3rd and 15th grade level; the average readability level was 8th grade. Ninety-four percent of the PEMs were rated either superior or adequate on text appearance, but 50% or more of the PEMs were rated inadequate on each of the other categories of the SAM criteria. Only 2 (11%) PEMs had the optimum suitability score of 70% or higher and 5th grade or lower readability level suitable for populations with limited HL. CONCLUSIONS: Commonly available cardiovascular PEMs used by some major healthcare institutions are not suitable for the average American patient. The true prevalence of suboptimal PEMs needs to be determined because it potentially negatively impacts optimal healthcare delivery and outcomes.