“Feasibility and acceptability of an enhanced psychological care intervention within cardiac rehabilitation services for patients with new-onset depressive symptoms compared to treatment as usual”

Depression is common in people with coronary heart disease (CHD), affecting up to 20% of individuals, approximately four times more common than in the general population. Such depression is associated with a doubling of risk of subsequent morbidity and mortality. The detection and appropriate management of depression among people with CHD is a policy priority. Although psychological health is part of cardiac rehabilitation, access to psychological care is patchy.

Our research aimed to address this gap in the provision of psychological support for people with depression, by developing and evaluating Enhanced Psychological Care (EPC), a complex intervention embedded within routine cardiac rehabilitation. Nurses identified patients with depressive symptoms and offered them Behavioural Activation – an established treatment for depression. Nurses were also trained in mental health care coordination.

First, we conducted a multi-method study to determine the feasibility and acceptability of implementing/experiencing EPC from the perspective of cardiac rehabilitation nurses and patients. Preliminary testing of EPC (four teams, nine patients) found EPC to be acceptable, although nurses found it difficult to deliver within their existing workload. The intervention was refined to reduce workload, and then tested in a small pilot version of a potential RCT. A pilot RCT further tested EPC and aimed to clarify uncertainties around participant recruitment and retention needed to design a future, randomised controlled trial (RCT). The following data were collected from patients at baseline, five months and/or eight months: demographic characteristics, medical/cardiac status, psychiatric diagnostic status, depression severity [Beck Depression Inventory (BDI-II)], anxiety (BAI), health-related quality of life (EQ-5D and HeartQoL), degree of BA (Behavioral Activation for Depression scale) and of satisfaction with treatment (Client Satisfaction Questionnaire).

A preliminary economic evaluation was conducted to pilot methods to collect data on costs. Five teams were randomly allocated to deliver EPC and three teams to deliver usual care (UC). Fifty-six of 614 patients screened were eligible for recruitment and 29 patients took part (67% of revised target sample size of 43), 15 of which were in the EPC arm and 14 were in UC. Nurses and patients were also asked to take part in interviews. At five months, the mean BDI-II score was reduced from baseline in both arms. At five months, the mean BAI score improved in both arms, health-related quality of life improved in both arms, and generic health-related quality of life remained largely unchanged in both arms.

At interview, patients and nurses acknowledged the importance of embedding psychological support within routine rehabilitation. However, significant organisational and workload constraints meant EPC was not practical in routine care. The total estimated cost of providing EPC (n=15) of was £13,384 i.e. estimated cost per participant of £959 (93% of total cost due to nurse training). Patients and nurses acknowledged the importance, and recognised the value, of having psychological support embedded within routine cardiac rehabilitation. Consideration should be given to delivering EPC by dedicated mental health workers, such as psychological wellbeing practitioners (PWPs), working closely with cardiac rehabilitation services.

Richards SH, Dickens C, Anderson R, et al. Assessing the effectiveness of Enhanced Psychological Care for patients with depressive symptoms attending cardiac rehabilitation compared with treatment as usual (CADENCE): a pilot cluster randomised controlled trial. Trials 2018;19(1):211. doi: 10.1186/s13063-018-2576-9 [published Online First: 2018/04/04]


on behalf of the CADENCE study team

‘Beet’ cardiovascular disease!

Green leafy vegetables, like rocket, spinach, lettuce and more commonly, beets (in the form of juice, concentrate, flapjack, or even bread!) are key elements of the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets which are considered to be beneficial for cardiovascular health and longevity. In fact, the consumption of such vegetables, which are high in nitrate, have been shown to elevate the production of the well-known physiological signalling molecule, nitric oxide (often reported as an increase in its main biomarker, plasma nitrite) and subsequently lower systemic blood pressure, enhance cerebral and tissue blood flow, reduce the oxygen cost of submaximal exercise and improve exercise tolerance in both healthy and diseased populations.

More specifically, the reductions in blood pressure reported after inorganic nitrate consumption, in many different food forms, are comparable to those observed after antihypertensive medication, but, unlike most prescribed treatment, no adverse side-effects have been noted. Dietary nitrate has also been shown to increase the limit of tolerance during exercise tests in patients with peripheral arterial disease, heart failure, angina and when oxygen availability or the carrying-capacity of the blood is compromised, such as in hypoxia, anaemia or following blood donation. In addition, improvements in cognitive function, particularly decision making and reaction time, have been noted after nitrate ingestion.

Older individuals and those with chronic disease (including metabolic syndrome) and risk factors for atherogenesis and vascular events are likely to have lower concentrations of plasma nitrite due to an impairment in endogenously-derived nitric oxide, so too are those who smoke tobacco and use antibacterial mouthwash regularly, and, therefore, the physiological effects afforded by nitrate ingestion may be attenuated.

Sinead McDonagh

A minimum dose of 5-6 mmol of naturally derived nitrate from the diet is recommended to enhance exercise performance and mitigate complications associated with disease, such as hypertension, reduced oxygen availability or delivery and cognitive function. The additional, acute consumption of polyphenols, particularly those found in red wine, may also be helpful in augmenting nitric oxide production and the vasculature.

In summary, to optimise the therapeutic and ergogenic benefits of nitrate ingestion, the supplementation regimen must be customised; the type of supplement, dose, health status and habitual activities of the individual should be considered carefully before implementation. So why not try a green leafy salad and a glass of red wine (in moderation!) to lower your blood pressure and ‘beet’ cardiovascular disease!

, Research Fellow, Primary Care Research Group, UEMS

McDonagh STJ, Wylie LJ, Vanhatalo A, Jones AM. The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite and exercise blood pressure. International Journal of Sports Medicine 2015; 36(14):, 1177-1185.

McDonagh STJ, Vanhatalo A, Fulford J, Wylie LJ, Bailey SJ, Jones AM. (2016). Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation. American Journal of Physiology – Heart and Circulatory Physiology 2016; 311:H1520-H1529.

McDonagh STJ, Wylie LJ, Webster JMA, Vanhatalo A, Jones AM. Influence of dietary nitrate food forms on nitrate metabolism and blood pressure in healthy normotensive adults. Nitric Oxide 2018; 72:66-74

McDonagh STJ, Wylie LJ, Morgan PT, Vanhatalo A, Jones AM. Effects of low and high polyphenolic alcoholic beverages consumed with a nitrate-rich meal on systemic blood pressure. Original Investigation (under review).

McDonagh STJ, Vanhatalo A, Wylie LJ, Jones AM. Potential benefits of dietary nitrate ingestion in healthy and clinical populations (under review).

Supporting patients at-risk from their asthma

Despite evidence-based guidelines and effective treatments, more than three people still die from asthma every day in the UK (Asthma UK, 2017). A 2014 National Review of Asthma Deaths report highlights that over three-quarters of deaths from asthma, and many asthma-related hospital admissions, are preventable through improved patient and medical management.

Following an asthma death at his practice in Norfolk, I supported a GP colleague with piloting an approach involving adding electronic flags to the records of asthma patients identified as “at-risk” and providing training to practice staff about responding to the flags, for example by facilitating timely access and providing opportunistic management (Noble et al, 2006). In a subsequent “At-Risk Registers In Severe Asthma” (ARRISA) study (Smith et al, 2012) a cluster randomised trial showed that across 29 GP practices this approach had no significant effect on the proportion of patients experiencing moderate-severe asthma exacerbations over 12 months (control: 47%; intervention: 54%). However, this composite outcome masked significant reductions in intervention patients experiencing hospitalisations, smaller reductions in A&E and out-of-hours contacts, plus improvements in prescribing of prednisolone for exacerbations and other aspects of care.

So, an adaptive, practice-level approach to improving management of at-risk asthma patients still appeared promising, but to provide more definitive evidence of effectiveness and cost-effectiveness we are now conducting a larger scale “At-Risk Registers Integrated into primary care to Stop Asthma crises in the UK” (ARRISA-UK) study. This cluster-randomised controlled trial aims to recruit 262 GP practices covering over 9,000 registered at-risk asthma patients across the UK. As previously, the intervention involves identification and flagging records of at-risk patients, but this time with web-based training used to support implementation of practice-wide actions in response to the flags. The study is powered to assess whether the intervention reduces the proportion of at-risk patients experiencing an A&E attendance, hospitalisation or death from asthma over 12 months.

By November 2017 184 practices had been recruited to the study, 10 in the South West, with 31 intervention practices completing the training and implementing flagging. Thank you to all local practices who have supported the study to date! Recruitment is continuing and please contact Tricia Holloway from the Local Clinical Research Network (, myself ( or the central ARRISA-UK team if you would like further information or your practice is interested in participating. Please also get in touch with any related research ideas!

Dr Jane Smith, Senior Lecturer in Primary Care (
ARRISA-UK South West Principal Investigator and Process Evaluation lead

International Society for Quality of Life Research (ISOQOL)

The 24th annual ISOQOL conference held in Philadelphia, USA, showcased exciting worldwide research through a mixture of symposiums, research talks, posters, special interest group (SIG) meetings and discussions/debates on patient-reported outcomes. This included psychometric validation of measures, operationalisation challenges and successes within clinical settings, advances in PRO data collection using modern technology and much more.

Professor Claire Snyder handing Presidential gavel over to Professor Jose M Valderas

There were plenty of opportunities to connect with and build on existing networks through the various SIG groups, providing attendees with updates on current and interesting future projects. This conference also saw the presidential gavel passed onto Professor Valderas from the University of Exeter Medical School’s Health Services and Policy Research Group, assuring ISOQOL members of a continued strategic leadership and ensuring the continued growth as a society.

Some of the conference highlights included plenary talks on the use of Patient-Reported Outcomes (PROs) in multimorbidity, cutting edge research examining innovative ways to research Quality of Life (QOL), ending with a thought-provoking discussion of two influential papers in the QOL literature and contemporary issues for researchers to consider.

Talks covered a variety of issues including analytical methods through IRT models of measurement and looking at minimal important change. There was a ‘tricks of the trade’ presentation looking at researcher’ experiences in disseminating their work.

Symposiums included qualitative methods in exploring Minimally Clinically Important Difference (MCID), integrating PRO data collection in patient records, and cognitive appraisal assessments in QOL research. Innovative techniques were being used across the globe for the collection of PRO data, utilising online technology-breaking IT systems barriers @KLIKproject, allowing more flexibility for hospitals with different IT systems to collect their own data. ISOQOL attendees have taken a forward thinking approach to their research which will bring interesting results to next year’s conference in Dublin (24-27 October 2018).

PhD student, HSPRG, UEMS

Ills, skills and pills

When we think of a pharmacist, the picture of a white-coated individual dispensing medication in our local chemist may come to mind. They may be back office, carefully checking medicines into white paper bags and then coming to the shop floor to offer over-the-counter advice. Traditionally they were the chemists making up lotions and potions. Yet, with their four years of Master’s level training with an additional pre-registration year, there is an increasing view that their potential in delivering healthcare has not been fully realised. In the busy environment of general practice with staff working to meet the myriad needs of patients, a variety of healthcare practitioners are needed. Considering the current trend of rising prescriptions and polypharmacy, a pharmacist within a general practice team may be of huge benefit. Naturally in this healthcare context, there will be pharmacists’ roles around pharmacy liaison, practice processes and quality improvement activities. There will also be opportunities for patient-facing consultations with pharmacists making diagnosis and writing prescriptions. To optimise the input of pharmacy expertise and to provide quality care, pharmacists in general practice will need to extend their skills in clinical assessments and reflective practice. The article ‘Ills, skills and pills’ discusses this further considering the challenges of extending pharmacists’ roles, pharmacists integrating into general practices and ensuring the safety of patient care.

Sims L, Campbell J. Ills, skills and pills: developing the clinical skills of pharmacists in general practice. 

Laura Sims 17.08.17

Summer internship

Over the months of June-August, I had the privilege to do a summer internship with the Health Services and Policy Research group during which I worked on one of their projects regarding Patient-reported outcome measures (PROMs). Joining Professor Valderas and his team was a great experience and I learnt a lot whilst being in a friendly and stimulating environment. My main responsibility was extracting data from clinical trials for a Cochrane systematic review that the team is currently working on. The review investigates the usefulness of providing regular PROMs feedback to healthcare professionals and how that could improve patient care. Although at times challenging, this task equipped me with valuable skills which will undoubtedly help me throughout the rest of my degree and further in my career. Another reason why the placement was so valuable is that I got a taste of what research is being done across the Exeter Collaboration for Primary Care (APEx) and how people with various areas of expertise work towards bettering care for patients together. Working with me also was Joe Coombes who looked at chronobiology and PROMs.

I would like to thank the Health Services and Policy Research group for being very welcoming and always offering to help! I hope to be back in the future either as a student or a researcher!

, BSc Medical Sciences student
September 2017

A blood platelet count could help to diagnose cancer earlier

baileyCancer is one of the greatest health concerns in the developed world, with approximately 14 million new cases per year across the globe.(1) In the UK, cancer survival is poorer than in the US and in many other European countries. Much research is focused on finding out why this is, and developing strategies to improve cancer outcomes in the UK. Diagnosing cancer earlier is a key strategy to improving survival for patients; when cancer is diagnosed at an earlier stage, it is easier to treat, and patients are likely to survive for longer.

The DISCO team, based at the University of Exeter Medical School, carries out research in the area of cancer diagnostics. We recently completed a study investigating platelet count as a potential diagnostic marker of cancer.(2) Platelets are small cells in the blood which are involved in blood clotting processes and in immune response. A normal platelet count is 150–400 x109/l; anything over 400 is a raised platelet count, known as thrombocytosis. The platelet count is measured as part of a routine blood test.

We found that thrombocytosis is an important risk marker of cancer. We compared the proportion of new cancer cases in two groups of patients; those with thrombocytosis and those with a normal platelet count. The results showed that 11% of men and 6% of women with thrombocytosis were diagnosed with cancer, compared to 4% of men and 2% of women with a normal platelet count.

These figures are exciting as they show that thrombocytosis could be used by general practitioners to identify patients to send for further investigation for cancer earlier; perhaps before other symptoms begin. In the study, a third of lung and colorectal cancer patients with thrombocytosis had no other ‘alarm’ symptoms that would have prompted cancer investigations in the year before they were diagnosed. If thrombocytosis was recognised as a risk marker of cancer, that third of lung cancer patients would have their diagnosis made earlier – which could make the difference in earlier diagnosis and longer survival.

Sarah Bailey
Research Fellow
DISCO group, University of Exeter Medical School

1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 Lyon, France: International Agency for Research on Cancer; 2013.

2. Bailey SER, Ukoumunne O, Shephard EA, Hamilton W. Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data. British Journal of General Practice.2017; 67 (659): e405-e413.

Rescuing the NHS – the top ten priorities

Professor John Campbell, Professor of General Practice and Primary Care, University of Exeter Medical School
Professor John Campbell, Professor of General Practice and Primary Care, University of Exeter Medical School

The NHS is deeply embedded in the social and cultural DNA of the nation – because it’s a caring, accessible, high quality service for all, and so is publicly funded through the tax system. The NHS is massively respected and valued  by the public, but the healthcare system is in crisis with particularly serious problems facing general practice, the ‘jewel in the crown’ of the NHS, and an essential part of health and social care in the UK. GPs deliver care which is cheaper than many other internationally-recognised models, and which results in improved clinical and patient-experience outcomes for the UK population. Whilst the Government, the BMA and the RCGP have produced a ten-point plan, many of the proposed solutions are, while laudable, just sticking-plaster options. A fundamental change in approach is needed and here’s my 10 priorities for change.

  1. Fund the system properly: if necessary raise taxes; prioritise GP funding with a target of 11% of healthcare spend.
  2. Revalue general practice and general practitioners: get rid of the drive towards 7 day working, it’s neither necessary nor desirable and it’s fundamentally flawed in evidence; manage the media- they are destroying general practice; pay GPs properly; use targets such as those in the Quality and Outcomes Framework for patient benefit, not to manage GPs.
  3. Reinvent ‘urgent’ and ’emergency’ care – and provide the highest possible quality accessible service for people who need such care.
  4. Expect ‘self-care’ – provide high quality support and resources and help for people who manage their own care and use the system well; support individuals and families in achieving this goal; reinvent personal responsibility for health; avoid patients being passive passengers.
  5. Invest in high quality social care for people in their own homes and community settings – fund care for older people and pay community-based carers properly.
  6. Use the available skill-set – encourage, support and fund the development of new roles and build on the existing high quality skill-set – for example, developing new career opportunities for pharmacists, physios, and nurses; use the high quality NHS management that is currently available; ensure NHS management’s organisational memory and expertise is recognised and retained.
  7. Examine healthcare spending carefully – invest in high quality treatments that will enhance people’s health and wellbeing; disinvest in massively expensive treatments that offer only marginal benefits.
  8. Work with experts – the BMA, the Royal College of General Practitioners, universities, and patient representative bodies – to help sort the problems; stop making GPs the scapegoat for a failing system of care; act on the recommendations of Health Education England’s Primary Care Workforce Commission.
  9. Train doctors better, in the kind of care needed by NHS patients – focusing on the complex care of an ageing population in which people with many co-existing health problems are the norm; medical students need more exposure to high quality, motivated general practice in programmes of training which are properly funded. Fund high quality training for doctors choosing general practice as a career (Health Education England is, like many public services, facing substantial cuts in budgets, and threatening to reduce spending in GP training at a critical moment in NHS history).
  10. Develop the health and healthcare evidence base by doubling funding in the high quality health research programmes delivered by the National Institute of Health Research, the research and development arm of the NHS which is funded by the Department of Health.

Professor John Campbell
University of Exeter Medical School

Interarm difference in blood pressure

Dr Chris Clark
Dr Chris

Dr Chris Clark writes: The difference in blood pressure between arms sometimes found in the surgery has been a longstanding research interest of mine. After joining the Mid Devon Medical Practice we were able to start studying it and demonstrated the first association of an interarm blood pressure difference with poorer survival outcomes in 2002. The subject has stayed with me ever since and each study throws as many questions as answers. We can look back over the 15 years and identify some areas of increased certainty and others still in need of research.

We now know that, where systolic blood pressure differs between arms by at least 5mmHg, there is likely to be a survival difference in unselected populations. One goal of our current international collaboration, INTERPRESS, is to address what might be the lower limit of an interarm difference that is associated with differences in survival.
We know that interarm differences are associated with peripheral artery disease, with cerebrovascular disease and in diabetes with both retinopathy and nephropathy.

A common criticism is that the interarm difference is not always reproducible on repeated measures. We do know that the method of measurement is important; if a blood pressure is measured sequentially there is likely to be a three-fold over-estimation of the presence of an interarm difference compared with measuring both arms simultaneously. We know that the white coat effect contributes to this overestimation as well so a repeated simultaneous method of assessment is the only way forward for further research.

We do not know the cause of an interarm difference. It is unlikely to be due simply to narrowing of one large artery in one arm. The competing hypothesis, which is gaining favour, is that arterial stiffness can be unevenly distributed between arms, particularly early in the course of hypertension, so we see differences for that reason. This could account for variability in interarm differences since stiffness has both static and dynamic components. We do lack robust imaging studies to show us the arteries in people with and without interarm difference and this is one area of research for us going forward.

I recently summarised evidence around interarm difference in an article entitled “Do we know enough yet” and it’s clear that whilst we know a lot there is plenty more to learn. Emerging areas of interest include the association of interarm difference with development of cognitive impairment, delineating the causes of and contributing factors to interarm difference, and describing how interarm difference relates to absolute blood pressures and prediction of cardiovascular risk. These are all goals which we are working towards in our INTERPRESS collaboration and we look forward to presenting findings from this project in 2018.

Dr Chris Clark June 2017

CEC is supported by an NIHR Clinical Lectureship award; INTERPRESS is supported by the NIHR Research for Patient Benefit programme, grant no: PB-PG-0215-36009.