Publications by authors named "Clare Murphy"

21 Publications

  • Page 1 of 1

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

Wellcome Open Res 2021 14;6:114. Epub 2021 May 14.

School of Healthcare Sciences, Cardiff University, Cardiff, CF14 4XN, UK.

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. 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. 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. 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.
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http://dx.doi.org/10.12688/wellcomeopenres.16744.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276184PMC
May 2021

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

JAMA Cardiol 2021 Jun 23. Epub 2021 Jun 23.

British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

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.
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http://dx.doi.org/10.1001/jamacardio.2021.1825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223134PMC
June 2021

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

Open Heart 2021 02;8(1)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

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.
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http://dx.doi.org/10.1136/openhrt-2020-001453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919592PMC
February 2021

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

ESC Heart Fail 2021 04 18;8(2):1324-1332. Epub 2021 Jan 18.

NHS Greater Glasgow and Clyde Heart MCN Heart Failure subgroup, Scotland, UK.

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.
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http://dx.doi.org/10.1002/ehf2.13209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006619PMC
April 2021

Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction.

J Am Coll Cardiol 2020 12;76(24):2817-2829

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

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 × min × mm Hg vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue × min × mm Hg; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue × min × mm Hg vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue × min × mm Hg; 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.
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http://dx.doi.org/10.1016/j.jacc.2020.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724570PMC
December 2020

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).

BMJ Open 2020 12 4;10(12):e040771. Epub 2020 Dec 4.

MRC/CSO Social and Public Health Sciences Unit and Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.

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.
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http://dx.doi.org/10.1136/bmjopen-2020-040771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722379PMC
December 2020

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).

Circulation 2021 Feb 13;143(6):516-525. Epub 2020 Nov 13.

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (M.M.Y.L., K.J.M.B., K.M., G.R., R.T.C., C.B., L.C., K.F.D., N.N.L., C.J.P., J.R.P., P.W., A.R., P.B.M., J.J.V.M., P.S.J., M.C.P., N.S.), University of Glasgow, United Kingdom.

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/m (=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/m (=0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%-47%), =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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864599PMC
February 2021

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

BJPsych Open 2020 Jan 28;6(1):e12. Epub 2020 Jan 28.

Director of England and Wales, Development and Delivery, The Mental Health Foundation, UK.

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.
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http://dx.doi.org/10.1192/bjo.2019.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001470PMC
January 2020

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

BMJ Open Qual 2019 28;8(3):e000676. Epub 2019 Aug 28.

Cardiology, Royal Alexandra Hospital, Paisley, Renfrewshire, UK.

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-. 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 '' which linked training to defined clinical service delivery. Further work is needed to assess the impact of the programme on long-term CVD outcomes.
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http://dx.doi.org/10.1136/bmjoq-2019-000676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730630PMC
August 2019

Emergency contraception in the UK: stigma as a key ingredient of a fundamental women's healthcare product.

Sex Reprod Health Matters 2019 Nov;27(3):1647399

ESRC PhD Candidate in Social Policy, School of Social Policy, Sociology and Social Research, University of Kent , Kent , UK.

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http://dx.doi.org/10.1080/26410397.2019.1647399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887978PMC
November 2019

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

Circ Cardiovasc Interv 2019 08 31;12(8):e007830. Epub 2019 Jul 31.

Department of Cardiology, West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, United Kingdom (M.M.Y.L., M.C.P., P.R., J.S., C.E.J., D.S.C., K.M., P.C., N.P.S., M.B.M., A.S., A.P.R., S.H.M.H., E.E.P., K.G.O., C.B.).

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.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.007830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664981PMC
August 2019

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).

Open Heart 2016;3(1):e000371. Epub 2016 Apr 20.

West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, UK; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; Western Infirmary, Glasgow, UK.

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).
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http://dx.doi.org/10.1136/openhrt-2015-000371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838768PMC
April 2016

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

Cell Rep 2013 Sep 5;4(5):898-904. Epub 2013 Sep 5.

Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.

The canonical Wnt signaling pathway, mediated by the transcription factor β-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 β-catenin-1 function, indicating that the two β-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 β-catenin. Finally, windorphen robustly and selectively kills cancer cells that harbor Wnt-activating mutations, supporting the therapeutic potential of this Wnt inhibitor class.
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http://dx.doi.org/10.1016/j.celrep.2013.07.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923627PMC
September 2013

Treated follicular lymphoma, recurrent invasive pneumococcal disease, nonresponsiveness to vaccination, and a unique pneumococcus.

Case Rep Hematol 2012 30;2012:386372. Epub 2012 Dec 30.

Department of Infectious Disease, Monklands Hospital, Monkscourt Avenue, Airdrie ML6 0JS, UK.

A nonneutropenic patient with treated low-grade non-Hodgkin's (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.
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http://dx.doi.org/10.1155/2012/386372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546434PMC
February 2013

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.

Trials 2012 Oct 4;13:184. Epub 2012 Oct 4.

University of Edinburgh/BHF Centre for Cardiovascular Science, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 SU4, UK.

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.
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http://dx.doi.org/10.1186/1745-6215-13-184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667058PMC
October 2012

Assessment of commonly available education materials in heart failure clinics.

J Cardiovasc Nurs 2012 Nov-Dec;27(6):485-94

Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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.
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http://dx.doi.org/10.1097/JCN.0b013e318220720cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007697PMC
April 2013

The Depressive Experiences Questionnaire as a measure of psychoanalytic constructs reported to be measured.

Psychol Rep 2009 Dec;105(3 Pt 1):714-20

University of Ghent, Department of Psychology and Educational Sciences, H. Dunantlaan 2, B-9000 Ghent, Belgium.

This study presents an empirical test of Coyne, Thompson, and Whiffen's statement that the Depressive Experiences Questionnaire does not measure the psychoanalytic constructs it is supposed to measure. Convergence was evaluated between the Depressive Experiences Questionnaire's Dependency and Self-criticism scales and clinicians' ratings on hysterical/anaclitic and obsessional/ introjective personality styles in a sex-balanced sample of 56 Flemish outpatients. In line with expectations from Blatt's research paradigm, convergence was observed between the Dependency scale and ratings on hysterical/anaclitic style in the full sample as well as female and male samples separately; convergence between the Self-criticism scale and ratings on obsessional/introjective style was only observed for men. This study yielded no evidence for divergence of the Depressive Experiences Questionnaire and Blatt's psychoanalytic theory. Research is needed to evaluate the sex-specific validity of these subscales.
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http://dx.doi.org/10.2466/PR0.105.3.714-720DOI Listing
December 2009

Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells.

PLoS One 2008 Aug 6;3(8):e2904. Epub 2008 Aug 6.

Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

Background: Pluripotent embryonic stem (ES) cells, which have the capacity to give rise to all tissue types in the body, show great promise as a versatile source of cells for regenerative therapy. However, the basic mechanisms of lineage specification of pluripotent stem cells are largely unknown, and generating sufficient quantities of desired cell types remains a formidable challenge. Small molecules, particularly those that modulate key developmental pathways like the bone morphogenetic protein (BMP) signaling cascade, hold promise as tools to study in vitro lineage specification and to direct differentiation of stem cells toward particular cell types.

Methodology/ Principal Findings: We describe the use of dorsomorphin, a selective small molecule inhibitor of BMP signaling, to induce myocardial differentiation in mouse ES cells. Cardiac induction is very robust, increasing the yield of spontaneously beating cardiomyocytes by at least 20 fold. Dorsomorphin, unlike the endogenous BMP antagonist Noggin, robustly induces cardiomyogenesis when treatment is limited to the initial 24-hours of ES cell differentiation. Quantitative-PCR analyses of differentiating ES cells indicate that pharmacological inhibition of BMP signaling during the early critical stage promotes the development of the cardiomyocyte lineage, but reduces the differentiation of endothelial, smooth muscle, and hematopoietic cells.

Conclusions/ Significance: Administration of a selective small molecule BMP inhibitor during the initial stages of ES cell differentiation substantially promotes the differentiation of primitive pluripotent cells toward the cardiomyocytic lineage, apparently at the expense of other mesodermal lineages. Small molecule modulators of developmental pathways like dorsomorphin could become versatile pharmacological tools for stem cell research and regenerative medicine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002904PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483414PMC
August 2008

Approaches to the treatment of anaemia in patients with chronic heart failure.

Heart Fail Rev 2008 Dec 8;13(4):431-8. Epub 2008 Apr 8.

BHF Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, Scotland, UK.

An association between anaemia, poor functional status and, compared to non-anaemic patients, worse clinical status and a higher risk of hospitalisation and death has been consistently reported in chronic heart failure (CHF), although cause an effect has not been proven. While it is attractive to think that correction of a co-morbidity that exacerbates already diminished delivery of oxygen to the tissues in heart failure is likely to beneficial, the possible haemodynamic effects of increasing haemoglobin, for example vasoconstriction, might not be. Consequently, the balance of benefit and risk of anaemia correction in CHF is uncertain, may vary according to the severity of anaemia (and other factors) and needs to be properly evaluated. To date, most studies of anaemia correction in CHF have used erythropoiesis stimulating agents (ESAs). The trials with erythropoietin have been of small size, uncontrolled or unblended/single blind, raising concerns again about interpretation of subjective outcomes. In addition, the analyses of these trials have been suboptimal. Two double-blind, placebo-controlled, darbepoetin studies have been published in full. Neither showed an improvement in functional capacity or consistent effect on patient reported symptoms/quality of life. Darbepoetin is, however, currently being tested in a large-scale, phase III morbidity and mortality trial, the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF) which should contribute important information of the safety and efficacy of ESAs in this syndrome. Other approaches, notably parenteral iron supplementation, are also being evaluated and other agents for anaemia correction are under development.
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http://dx.doi.org/10.1007/s10741-008-9085-yDOI Listing
December 2008

Anemia and heart failure.

Curr Heart Fail Rep 2004 Dec;1(4):176-82

Department of Cardiology, Western Infirmary, Glasgow G11 6NT, UK.

Over the past few years, anemia has emerged as a powerful independent predictor of adverse outcomes in chronic heart failure (CHF). It affects up to 50% of patients with CHF, depending on the definition of anemia used and on the population studied. Even small reductions in hemoglobin are associated with worse outcome. However, the causes of anemia in CHF remain unclear, although impairment of renal function and inflammatory cytokines are proposed mechanisms. Both may act through impairment of the synthesis or action of erythropoietin. Preliminary studies have demonstrated improvement in symptoms, exercise tolerance, quality of life, and reductions in hospitalizations when patients with severe CHF were treated with erythropoietin. The benefits and the potential risks of such therapies will be further addressed in upcoming larger randomized trials. The recent interest in anemia reflects a new perspective in heart failure therapy, focusing on non-cardiovascular comorbidities.
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http://dx.doi.org/10.1007/s11897-004-0006-7DOI Listing
December 2004
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