Scoping Research on Models of Care to Support Earlier Diagnosis of Diseases Related to Breathlessness As a Symptom

SCOPING RESEARCH ON MODELS OF CARE TO SUPPORT EARLIER DIAGNOSIS OF DISEASES RELATED TO BREATHLESSNESS AS A SYMPTOM

Peter J Aspinall

Bayswater Institute and University of Kent

August 2014

Contents

Acknowledgements 3 Executive Summary 4 Key messages 7

1. Introduction 9 1.1 Background and context 9 1.1.1 Living Longer Lives 9 1.1.2 Breathlessness 10 1.2 Research requirements 11 1.2.1 Objectives 11 1.2.2 Research Questions 11

2. Methods 12

3. Results 13

3.1 Early diagnosis 13 3.1.1 COPD 13 3.1.2 Lung cancer 17 3.1.3 Asthma 21 3.1.4 Obesity 27 3.1.5 Patient experience 27 3.2 The ‘rapid access clinic’ model 31 3.2.1 Rapid access chest pain clinics 31 3.2.2 Rapid access clinics for arrhythmias, blackouts, palpitations, & murmur 40 3.2.2.1 Rapid access palpitations clinics 41 3.2.2.2 Rapid access blackout clinics 42 3.2.2.3 Rapid Access Arrhythmia/Atrial Fibrillation Clinics 44 3.2.2.4 Heart Murmur Clinics 46 3.2.3 The first long-term findings of rapid access clinics 47 3.3 Breathlessness 49 3.3.1 Symptom-based vs disease-based approach to assessment and diagnosis 50 3.3.2 Investment and disinvestment decisions for breathlessness 53 services: prerequisites 3.3.3 What is needed to assess breathlessness 54 3.3.4 Examples of current models 55 3.3.5 Pathways 60

4. Discussion and Conclusions 65

Acknowledgements

This study was commissioned by NHS Improving Quality (NHS IQ) from the Bayswater Institute, a small independent research institute and charity founded in 1991 that focuses on the implementation of policies within organisations, the dissemination of new practices, and the management of organisational change. It has over 20 years’ experience of work within the NHS on organisational change and in particular the adoption of new health technologies. The principal investigator for the study is Peter Aspinall, Senior Analyst at the Bayswater Institute and Emeritus Reader in Population Health in the Centre for Health Services Studies, University of Kent.

Thanks are due to Vanessa Brown and Mel Varvel of NHS IQ and Professor William Maton-Howarth and Professor Ken D Eason of the Bayswater Institute for helpful comments on a draft of this report. I am also grateful to: Siân Williams, Executive Officer of the International Primary Care Respiratory Group and Member of the London Respiratory Clinical Leadership Group, for an opportunity to discuss the IMPRESS algorithm, and to Wendy Fairhurst and Jay Mangan for information about the NHS Ashton, Leigh and Wigan proposal for diagnosing breathlessness.

Executive Summary

The scoping research was framed around a number of questions: (i) What evidence or good practice exists on early diagnosis and its impact on the quality of patient care (patient safety, outcomes and experience) and costs to the health service? (ii) What evidence, evaluation and/or models are there for diagnosis of disease from a symptom-based perspective? (iii) What models, standards, guidelines or good practice already exist for ‘rapid’ access to diagnostics generally, e.g. Rapid Access Chest Pain Clinics? (iv) What evidence, evaluation and/or models are there for diagnosing disease by focusing on breathlessness in particular as a symptom? Are there any rapid access breathlessness clinics and/or diagnostic pathways for breathlessness already in existence or in development?

With respect to early diagnosis, the following conditions where breathlessness is a symptom - Chronic Obstructive Pulmonary Disease (COPD), Lung Cancer, Asthma, Obesity, Heart Failure, and Atrial Fibrillation - were investigated. With respect to COPD, the literature identified a range of examples, including targeted case finding vs open spirometry and use of new diagnostic technologies. The searches for literature on the early diagnosis of lung cancer yielded the example of the instigation of a multidisciplinary lung investigation day in a Birmingham trust which was associated with significant reductions in the number of patients requiring bronchoscopy and in the time from presentation at the rapid access clinic to both histological diagnosis and presentation to the multidisciplinary team meeting. Prompt access to radiology and pathology services was found to be key. The literature on the early diagnosis of asthma and obesity yielded few relevant examples, except in children and that on early diagnosis of cardiac conditions is addressed in the section on rapid access clinic models.

The literature provides examples of models, standards, and good practice that already exist for ‘rapid’ access to diagnosis of disease from a symptom-based perspective, notably, chest pain, atrial fibrillation, blackouts, palpitations, breathlessness, and murmur. There are many rationales for rapid access chest pain clinics (RACPCs), including inappropriateness of some emergency department referrals; diagnostic delay resulting from outpatient appointment waiting lists; and most general practitioners’ (GPs) insufficient confidence in interpreting exercise tolerance test (ETT) results and difficulty in diagnosing coronary artery disease if symptoms are non-specific / vague or if the disease is silent. The primary objective of these clinics is ‘to help ensure that people who develop new symptoms that their GP thinks might be due to angina can be assessed by a specialist within two weeks of referral’.

Amongst findings relevant to the configuration of diagnostic services for breathlessness, RACPCs effectively identify patients at increased coronary risk but fail to correctly diagnose all patients. Long- term review data show that diagnoses with a cardiac cause for chest pain, non-cardiac chest pain, and other diagnoses remained in a narrow range, suggesting consistent patterns of diagnosis. The major purpose of rapid assessment of chest pain is that it should provide access to invasive investigation equitably for all patients in whom it is indicated, though inequities exist with respect to access, referrals for coronary angiography, and use of ETT, suggesting suboptimal outcomes. RACPCs should substitute for existing services and reduce to zero referrals to outpatient cardiology clinics (OPCCs), though these are continuing at a reduced level. An appointments system and clear guidelines are needed to secure appropriate referrals. Lack of staff prevents RACPCs from offering an open access daily service. Standardisation of data collection is needed to facilitate the running of RACPCs, auditing, and provision of a core dataset. The best skill-mix for clinics and allocation of functions requires investigation in the context of costs, clinical management and diagnosis, and continuity of care. Finally, more rapid assessment of patients with chest pain might require increasing levels of awareness among the general population about the significance of new onset chest pain.

The rationale for rapid access clinics for arrhythmia, atrial fibrillation, palpitations, blackouts, and murmur are similar. Rapid access arrhythmia clinics provide a rapid diagnosis, stratify risk, and enable prompt initiation of evidence-based treatments for patients presenting with suspected new cardiac arrhythmias. Stable patterns of diagnosis over a decade have been reported. Rapid access palpitations clinics are effective at establishing a range of common diagnoses, though with a longer time from referral to assessment. Rapid access blackouts clinics effectively distinguish between epilepsy, syncope and psychogenic causes, though diagnosis is elusive in up to 40% of cases, without the need for onward specialist referral; provide rapid triage to the right care pathway; and avoid overreliance on more sophisticated investigations. No substantive studies have been identified of heart murmur clinics. All these clinics are generally viewed positively by patients and primary care physicians.

There are a number of models in existence or being developed for diagnosing disease by focusing on breathlessness as a symptom, including rapid access breathlessness clinics and diagnostic pathways for breathlessness. Rationales for developing breathlessness clinics include the fact that care pathways for aspects of breathlessness tend to be disease-specific and do not take satisfactory account of multi- morbidity, though cost-effectiveness data is lacking. Harmonisation of approaches across diseases is needed to reduce current unwarranted variation in diagnostic rates, systematic review evidence having shown that cross-boundary working can increase the speed of diagnosis. Such clinics have the potential to focus diagnostic services on symptoms at the point where people present to primary care, to address multi-morbidity, and the complex interaction and need for parity of esteem between mental and physical health.

Prerequisites for investment/disinvestment decision-making with regard to configuring breathlessness services, as suggested by IMPRESS1, include a need for a shared knowledge of the evidence base, consideration of where breathlessness services should be located, a ‘decision conference’ to develop symptom-based pathways with local experts, encouragement and fostering of integration across specialties, and assessment of local provision against the IMPRESS algorithm, an evidence-based integrated approach to assessment and treatment for breathlessness. New breathlessness services may be configured by the redesign of breathless diagnostic and assessment pathways; the commissioning of new services like dedicated earlier diagnosis breathlessness clinics; and the provision of such assessment services by all practices vs. selected practices with a special interest in breathlessness. IMPRESS suggests two organisational models: a federated model, with each general practice providing a core service, and then referring to a triage or primary care practitioner with a special interest; a breathlessness assessment service commissioned from a local hospital that has diagnostic equipment such as echocardiography and chest X-ray on site. It is unlikely that one organisational model will fit all circumstances and that models will evolve to reflect local resources, local needs, and the priorities set by consultants, hospitals, and clinical commissioning groups.

Currently, nearly all breathless patients present in primary care. The GP may initiate a range of investigations: peak expiratory flow rate (PEFR), spirometry, electrocardiography (ECG), brain natriuretic peptide (BNP) (if heart failure is suspected) and (if results are abnormal abnormal) referral for echocardiography which (if abnormal) results in an automatic cardiology outpatient referral. The length of time and amount of resources to achieve an accurate diagnosis for complex patients are drawbacks, high numbers of patients being currently misdiagnosed and receiving incorrect treatment.

1 IMPRESS (Improving and Integrating Breathlessness Services) is a joint initiative between the two leading respiratory clinical societies in the UK: the British Thoracic Society and the Primary Care Respiratory Society (PCRS)-UK. See: http://www.impressresp.com/#sthash.MgvVsbb0.dpuf

The searches of the literature identified few well-described examples of diagnostic breathlessness clinics and none with outcomes or cost-effectiveness analysis.

The new models include:

. An outpatient breathlessness clinic, run jointly by cardiology and respiratory consultants at the University Hospital of North Staffordshire National Health Service (NHS) Trust, which provides new assessments and follow-up appointments for unexplained breathlessness; . A GP referral to a one stop shop diagnostic service to improve diagnosis, set up by Ashton, Leigh and Wigan NHS, encompasses diagnosis (to improve COPD, asthma, and heart failure diagnosis) and enhanced care: breathless patients with diagnostic uncertainty (aged >50 with a past medical history of ischaemic heart disease or diabetes in primary care) are referred; an estimated 85% of cases require no specialist; . A hospital clinic-based dyspnoea examination programme for general practice offered patients with dyspnoea of at least 2 weeks duration a dyspnoea examination programme based in a hospital clinic in Haderslev Hospital, Denmark. All patients were examined within 2 weeks of referral, all examinations in an individual patient taking place on the same day. Concordance of the diagnosis on referral and the diagnosis based on the examination programme was found in only 39% of patients; . A new one-stop breathlessness clinic run by the service leads for Cardiology and Respiratory Medicine at Chelsea and Westminster Hospital caters for breathless patients who may have underlying cardiac and/or respiratory pathology where there is diagnostic uncertainty or where dual input is required. Access to the clinic is available via Choose and Book; . The unexplained breathlessness service at Royal Brompton and Harefield NHS Foundation Trust is a comprehensive, one-stop assessment to establish the cause of the patient’s breathlessness. It is run by a multi-disciplinary team with specialist experience and uses advanced tests, including a cardiopulmonary exercise test (CPET); . Barnet Clinical Commissioning Group’s northern network is developing a service level agreement for selected practices to provide spirometry, ECGs and 24 hour blood pressure monitoring. The service is intended to release capacity in general practice, to make best use of skills and resources, to be cost saving, and to benefit patients by earlier diagnosis, reducing waiting times, and avoiding hospital visits; . Finally, a diagnostic pathway for undiagnosed breathlessness is provided for NHS Bolton’s rapid access breathlessness clinic, though the relationship of the rapid access breathlessness clinic to primary and secondary care is not fully described in the documentation available.

There is no consensus on the optimal pathway for the diagnosis of breathlessness as the evidence base is weak/non-existent for newly implemented models or those in development. Diagnostic pathways (algorithms) have been published for some of the new models, including Ashton, Leigh, and Wigan NHS (which specifies patients with diagnostic uncertainty for referral), Papworth Direct One Stop Service Breathlessness Pathway (which offers no filtering of patients before referral); and NHS Bolton Breathlessness Pathway. The IMPRESS non-linear algorithm is the only pathway that is fully evidence-based, focusing substantially on precision with respect to each stage of the assessment rather than upon any major reconfiguration of services as new models. In the absence of cost-effectiveness data, the team worked up the algorithm de novo, including an extensive literature review. The algorithm starts with the question: should the patient be admitted, then tracks through assessment/diagnostic stages to referral to a specialist clinic.

Key messages for NHS Improving Quality

. There is a clear dearth of evidence in the literature on all four research questions, especially that relating to early diagnosis.

. With respect to the rapid access clinic model in general, there is a need for more research on the effectiveness of different organisational arrangements, on clinical outcomes, continuity of care, and costs.

. The evidence base on some of these rapid access clinics is very limited, with only one or two substantive studies, so it is difficult to draw relevant findings for breathlessness clinics. For example, we do not know how many rapid access clinics for arrhythmia/atrial fibrillation there are in the United Kingdom (UK) and most of our knowledge relates to just one clinic (Charing Cross, set up in 2002). Data for this clinic is limited to patient throughputs and diagnostic yield, with no cost-effectiveness data.

. With respect to rapid access palpitations clinics, again the evidence is limited to one substantive study with limited information on how referrals are made to the RAPC (including self-referral), what determines these referrals, how many RAPCs there are in the UK, and the benefits/drawbacks of integrating these various symptom-based clinics.

. Nevertheless, these rapid access clinics offer some important findings with respect to constancy in diagnostic yield, equity of access, and substitutability.

. They offer sufficient evidence for this review to recommend that there should be national standardisation of data collection and a computerised database at all clinics to assist with local management and the central collection and analysis of performance data aimed at monitoring and optimising management.

. The review also recommends the need to increase public awareness of the symptoms of breathlessness more widely than in the current pilot of two northern towns.

. Only a few models of breathlessness clinics were identified in the literature and several of these were still in development. There is no patient outcomes or robust cost-effectiveness data for any of these models. The cost-effectiveness data for the Ashton, Leigh and Wigan service was based on modelled estimates from other service data and is unlikely to be sufficiently reliable for this purpose. Independent evaluation is needed to compare costs and benefits of different service configurations. However, the lack of such data should not stall the introduction of rapid access breathlessness clinics or new diagnostic pathways as these are likely to be tailored to local circumstances and needs.

. The models identified fall within the two organisational types identified by IMPRESS: a federated model, with each general practice providing a core service, and then referring to a triage or primary care practitioner with a special interest; a breathlessness assessment service commissioned from a local hospital that has diagnostic equipment such as echocardiography and chest X-ray on site. Most fall within the latter category and are based on the rapid access one stop shop model. There are some commonalities: Chelsea and Westminster and North Staffs are similar in being developed as joint initiatives by cardiologists/respiratory clinicians,

perhaps providing an opportunity for collective learning. Further, some of the models select for patients where there is diagnostic uncertainty, while others do not filter patients.

. The IMPRESS algorithm is currently the only available evidence-based pathway, to which reference should be made in new model and diagnostic pathway development.

1. Introduction

1.1 Background and context

1.1.1 Living Longer Lives

NHS Improving Quality’s Living Longer Lives programme is currently commissioning a number of major transformational improvement programmes, all of which aim to reduce the number of people who die too soon from illnesses that could have been prevented or treated. These programmes of work are aligned with the NHS and Public Health Outcomes Frameworks, and contribute towards meeting the Government’s ambition to avoid an additional 30,000 premature deaths each year to 2020.

The major focus for these programmes is achieving a reduction in premature mortality from the nation’s biggest killers, heart disease and stroke, cancer, and liver and respiratory disease, and to work towards ensuring that England’s rates of premature mortality for these diseases move from being among the worst in Europe to being the best. Although research points to a number of strategies to improve outcomes in this area, one strategy common to most improvement programmes is increasing early diagnosis of disease to improve the scope for successful treatment.

Diagnostic testing is an integral part of the healthcare system, providing essential information to enable providers and patients to make the right clinical decisions. Currently, around three-quarters of clinical decisions are based on a diagnostic test. Demand for access to quicker and more accurate diagnostic tests is rising at a rate of ten per cent per year, increasing costs and placing significant pressure on the system. Improving the speed and accuracy of diagnosis is likely to make an important contribution to addressing the current need to deliver more, better quality healthcare with fewer resources2.

From a patient and carer perspective, early detection and diagnosis can prevent unnecessary pain and suffering, but it can also reduce the scale and cost of treatment. Evidence suggests that early diagnosis can lead to measurable health gains such as improved survival rates, as well as lower treatment costs. However, effective implementation of early diagnosis varies widely across the NHS and lags behind many other European countries. In 2010, the Department of Health estimated that if cancer patients in the UK were diagnosed at the equivalent stage of their disease as their European counterparts, up to 10,000 deaths could have been avoided.

Raising public awareness of symptoms and early diagnosis of disease is one of three themes in the Living Longer Lives programme. For the most part, programmes under this theme have focused on raising awareness and improving diagnosis of symptoms pertaining to a particular clinical condition or disease, e.g. the Be Clear on Cancer campaign. This is in part because of much of the work is driven by partners/stakeholders who have legitimate, vested interest in realising improvement in a particular area, e.g. the major healthcare charities. However, it is also a result of the fact that referral pathways, services, and payment systems in the NHS are largely organised around clinical specialities and do not readily accommodate patient referrals within and between specialities, or facilitate clinical collaboration or organisational integration.

2 Deloitte UK Centre for Health Solutions. Working differently to provide early diagnosis - Improving access to diagnostics (pdf). 2013.

1.1.2 Breathlessness

Given the need for further improvement in preventing premature mortality and the current interest in person-centred or integrated care, attention is now turning to raising public awareness of symptoms common to a number of conditions which could be prevented or treated more successfully through earlier diagnosis, and to facilitating referral pathways and services which provide joined up care so that patients are not passed ‘from pillar to post’ through the system in order to undergo the necessary diagnostic tests and to receive the correct treatment.

Next to pain, breathlessness is the most common symptom for which patients seek help and relief from their doctor. Approximately two thirds of cases of breathlessness in adults are due to a pulmonary or cardiac disorder. In about a third of cases, diagnosis will be multifactorial. 70% of all terminal cancer patients suffer breathlessness in their last six weeks.

In view of the focus on symptoms and the epidemiology of breathlessness in particular, NHS IQ’s Living Longer Lives team is in the process of designing a specific programme of work to pilot new models of care which improve access to services to facilitate earlier diagnosis and treatment for people who experience breathlessness as a symptom.

The Business Plan for NHS IQ for 2014/15 states that “we will pilot ‘rapid access’ models for breathlessness clinics in 3 areas in 2014/15 and evaluate outcomes before rolling out new models from 2015-18”.

The ‘rapid access clinic’ model was popularised by the publication of the National Service Framework for Coronary Heart Disease in 2000 which resulted in widespread development of rapid access chest pain clinics (RACPCs) to provide specialist assessment within two weeks of GP referral. However, the main focus of these clinics is to improve patient access to cardiology services in particular, rather than to facilitate rapid access to any/all appropriate diagnostic tests or treatment services related to the symptom ‘chest pain’. RACPCs offer one potential model for further exploration but the main focus for the breathlessness work is the concept of rapid access to diagnostics to facilitate earlier diagnosis leading to a better prognosis, not the RACPC (or any other model) per se.

The term ‘breathlessness clinic’ is often used to describe services provided to help people with chronic conditions to manage their breathlessness in the context of palliative care. However, the focus for this piece of work is on designing and evaluating new models of care for diagnosis, and not for the management of symptoms.

Public Health England has recently undertaken a breathlessness campaign pilot in Oldham and Rochdale, from 24 February to 23 March 2014, using local press, radio and posters with the message ‘if you’re getting breathless doing things you used to be able to do easily then go and see your GP’. The campaign evaluation will attempt to tease out the range of clinical conditions or causes of breathlessness of people presenting to their general practitioner in response to the campaign. It will also inform the development of rapid access diagnostic services for people with breathlessness and the value of future regional and national awareness raising campaigns.

1.2 Research requirements

1.2.1 Objectives

The primary aim of the pilot work is to explore the barriers to earlier diagnosis for people with the symptom ‘breathlessness’ and to test new models of care which address these barriers, facilitate rapid access to diagnostics, and help to obtain an accurate diagnosis in an efficient and effective way.

The purpose of this scoping research is to contribute to the development of the breathlessness pilots by helping NHS IQ to:

• Understand and apply ‘best practice’ in models of care from the UK and internationally for early diagnosis of disease both generally and with a focus on breathlessness as a symptom;

• Learn from past and present models of care (both successful and unsuccessful) relating to the above;

• Horizon scan/ consider how emerging trends and developments in this area might potentially affect the NHS IQ pilots, to help develop new insights and to think ‘outside the box.’

The insight gathered through the scoping exercise will be pivotal in NHS IQs development of a business case for any extension/expansion of the pilot work going forwards.

1.2.2 Research questions

The scoping research was framed around a number of questions:

• What evidence or good practice exists on early diagnosis and its impact on the quality of patient care (patient safety, outcomes and experience) and costs to the health service?

• What evidence, evaluation and/or models are there for diagnosis of disease from a symptom- based perspective?

• What models, standards, guidelines or good practice already exist for ‘rapid’ access to diagnostics generally, e.g. Rapid Access Chest Pain Clinics?

• What evidence, evaluation and/or models are there for diagnosing disease by focusing on breathlessness in particular as a symptom? Are there any rapid access breathlessness clinics and/or diagnostic pathways for breathlessness already in existence or in development?

The intention was to include relevant evidence/examples from the UK and internationally, both published/unpublished, pertaining to any/all healthcare settings, e.g. primary care, community, secondary care.

All models of care were of interest, but the primary focus of this work is diagnostic breathlessness clinics. There are already many ‘breathlessness clinics’ in existence but most of these focus on the management of breathlessness as a condition, particularly in relation to end of life care. These symptom management clinics were outside the scope of this work.

2. Methods

The methodology used to compile this report is a narrative review/evidence synthesis, focused specifically on the research questions. This draws on components from a range of methodological approaches, including, for example: the use of systematic review methodologies to search the literature through the specification of inclusion/exclusion criteria and the systematic extraction of a set of information from each of the publications that are in-scope. It also draws from the methodology of realist synthesis3, notably, the explanatory aim of realist review: ‘what works (size of effect), for whom, in what circumstances, in what respects, and how?’ A systematic review was not regarded as the most appropriate methodology, given the likely complexity of the interventions, breadth and volume of the literature, and multiple focuses required.

A wide range of sources was searched, all available as e-resources at the University of Kent. The full- text of most medical and health services research journals was also available via the University of Kent’s e-resources. Use was also made of NICE’s Clinical Knowledge Summary on Search Strategy for Breathlessness (last revised August 2010)4. To ensure comprehensive coverage, search strategies used in the published journal literature and Cochrane Library reviews were also reviewed.

The following literature sources were searched: The Cochrane Library (including Cochrane Databases of Systematic Reviews and protocols, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Database of Abstracts of Reviews of Effects (DARE), The Health Technology Assessment Database, and NHS Economic Evaluation Database, and postings of relevant Cochrane Review Groups such as Acute Respiratory Infections); National Institute for Health and Care Excellence (NICE) Evidence Search: https://www.evidence.nhs.uk/; Health Technology Assessment Programme resources: http://www.nets.nihr.ac.uk/programmes/hta; National Institute for Health Research (NIHR) Journals Library: http://www.journalslibrary.nihr.ac.uk/; Medline [Pubmed], using appropriate Boolean and other search algorithms; Embase, using appropriate Boolean and other search algorithms; searches of the internet using advanced search algorithms available in Google and Google Scholar, encompassing use of text strings and Boolean searching, and Scirus, a search engine for quality website information; British Thoracic Society: Topic specific literature searches; Royal College of Radiologists: Topic specific literature searches; hand-searching of recent (post 2005) copies of relevant journals use of their reference lists; and searches using Web of Knowledge Citation Indices. In addition telephone consultations were undertaken with some organisations (including IMPRESS) and networking to identify models of breathlessness clinics. The DIPEx database was searched for examples of patient experience with respect to the early diagnosis of diseases related to breathlessness as a symptom.

Information was systematically extracted from relevant studies and a research synthesis undertaken around a number of themes or research questions. These are presented in the results section of the report on early diagnosis of diseases where breathlessness is a symptom; the rapid access clinic model; and examples of new models and pathways.

3 Pawson R, Greenhalgh T, Harvey G, Walshe K. Realist Synthesis: An Introduction. Submitted to the ESRC Research Methods Programme Working Paper Series. Manchester: ESRC Research Methods Programme, 2004 (August). 4 http://cks.nice.org.uk/breathlessness#!searchstrategyforpublication

3. Results

3.1 Early Diagnosis

The specification for the scoping research included the research question on evidence or good practice on early diagnosis and its impact on the quality of patient care (patient safety, outcomes and experience) and costs to the health service. In discussions with NHS IQ, the scope of this research question was felt to be too wide, as it would encompass early diagnoses of all diseases and conditions, including the very extensive NHS screening programmes. It was therefore decided to focus on those conditions where breathlessness is a symptom, notably: COPD, lung cancer, asthma, obesity, and heart failure. A variety of sources were searched, including the Cochrane Library, National Institute for Health Research (NIHR) Journals Library (which includes the ‘health services and delivery’ journal), and Medline. The search term ‘early diagnosis’ was used to capture relevant studies.

3.1.1 COPD

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of disability, admission to hospital, and premature mortality. Though general practice is well positioned to diagnose and manage COPD, a significant gap between evidence and current practice has been documented, including a low level of awareness and implementation of clinical practice guidelines. Sometimes symptoms are attributed to the normal consequences of aging. While the optimum strategy for identifying patients with COPD remains to be determined, early diagnosis is widely regarded as central to the management of COPD. Under-diagnosis of COPD appears to be common (although the degree of underdiagnosis is rarely measured) and is a global problem5, limiting the benefit that could potentially be achieved through early intervention strategies, including smoking cessation, dietary advice, and exercise. For example, Shahab et al. (2006) provide the first national estimate of the extent of underdiagnosis of COPD in England: even with an inclusive definition of self-reported diagnosis, more than 80% of all cases did not report a clinical diagnosis and that, even in the severe or very severe category, only 50% appear to have been clinically diagnosed6.

The importance of identifying chronic obstructive pulmonary disease (COPD) at an early stage is widely recognised. The literature (including 13 studies reported in the Cochrane Collaboration) focuses on a number of topics, including early diagnosis through targeted case finding to measure underdiagnosis; early intervention for chronic obstructive pulmonary disease by practice nurse- general practitioner; an approach from the UK that used a nurse‐led community respiratory assessment unit offering spirometry and diagnostic support for primary care physicians; use of new diagnostic technologies (whether use of a mini-spirometer which can predict a diagnosis of COPD and use of impulse oscillometry in detecting early manifestations of COPD); and screening for suspected chronic obstructive pulmonary disease with a pre-interview questionnaire.

5 Dal Negro R, Berto P, Tognella S, Quareni L, Global Outcomes in Lung Disease Study Group. Cost-of-illness of lung disease in the TriVeneto Region, Italy: the GOLD Study. Monaldi archives for chest disease 2002; 57(1): 3-9. 6 L Shahab, M J Jarvis, J Britton, R West. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006; 61:1043–1047. doi: 10.1136/thx.2006.064410.he TriVeneto Region, Italy: the GOLD Study. Monaldi archives for chest disease 2002; 57(1): 3-9.

To document the extent of underdiagnosis in a high risk group of ambulatory patients, Tonkelman, Price et al. (2007)7 performed spirometry in smokers aged 40 years and over drawn from general practices in two countries (primary care practices in Aberdeen, Scotland, and Denver, Colorado). Current and former smokers aged 40 or older with no prior diagnosis of chronic obstructive respiratory disease (and no respiratory medications within the past year) were enrolled. Participants underwent pre- and post-bronchodilator spirometry. Spirometric examination was complete in 818 patients, of whom 155 (18.9%) had a study diagnosis of COPD. Using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity criteria, the COPD was mild in 57.4%, moderate in 36.8%, and severe in 5.8%. No patients had very severe disease according to GOLD criteria. The investigators conclude that screening of smokers over 40 in general practice may yield 10 - 20% undiagnosed COPD cases, with a substantial proportion of these having moderate to severe disease. Thus, earlier diagnosis through targeted case-finding will allow early, aggressive smoking cessation efforts and may lead to a reduction in the burden of COPD symptoms and a reduced impact of the disease on health-related quality of life in these patients.

Improved and easily accessible identification of individuals at risk of COPD in primary care is needed to select patients for spirometry more accurately. Thorn, Tilling et al (2012)8 assess improved prediction of COPD in at-risk patients using lung function pre-screening in primary care. Specifically, they explore whether use of a mini-spirometer can predict a diagnosis of COPD in patients at risk of COPD in primary care, and to assess its cost-effectiveness in detecting patients with COPD. Primary care patients aged 45-85 years with a smoking history of >15 pack-years were selected and data collected on the Clinical COPD Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale, and smoking habits. Lung function was measured by mini-spirometer (copd-6), followed by diagnostic standard spirometry. Time consumed was recorded. A total of 305 patients (57% females) of mean (Standard Deviation (SD)) age 61.2 (8.4) years, mean (SD) total CCQ 1.0 (0.8) and mean (SD) MRC 0.8 (0.8) were recruited from 21 centres. Screening with the copd-6 device was found to significantly predict COPD. Using the copd-6 as a pre-screening device, the rate of COPD diagnoses by standard diagnostic spirometry increased from 25.2% to 79.2%. Gender, CCQ, and MRC were not found to predict COPD. The copd-6 might therefore be an important device for pre-screening of COPD in primary care and may reduce the number of unnecessary spirometric tests performed.

While spirometry is used to diagnose chronic COPD, Frantz, Nihlen, et al (2012)9 assess whether impulse oscillometry may be of value in detecting early manifestations of COPD. The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD. The investigators examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD and subjects with or without COPD diagnosed according to the GOLD criteria. From a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases. The investigators concluded that self-reported

7 Tinkelman DG, Price D, Nordyke RJ, Halbert RJ. COPD screening efforts in primary care: what is the yield? Primary care respiratory journal 2007; 16(1): 41-8. See also Cochrane Collaboration: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/clcentral/articles/412/CN-00578412/frame.html 8 Thorn J, Tilling B, Lisspers K, Jorgensen L, Stenling A, Stratelis G. Improved prediction of COPD in at-risk patients using lung function pre-screening in primary care: A real-life study and cost-effectiveness analysis. Primary care respiratory journal 2012; 21(2): 159-66. See also Cochrane Library: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/clcentral/articles/410/CN-00900410/frame.html 9 Frantz S, Nihlen U, Dencker M, Engstrom G, Lofdahl CG, Wollmer P. Impulse oscillometry may be of value in detecting early manifestations of COPD. Respiratory medicine 2012; 106(8): 1116-23. Also Cochrane Library: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/clcentral/articles/448/CN- 00900448/frame.html

14 chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may therefore have the potential to detect pathology associated with COPD earlier than spirometry.

Two Australian studies focus on the use of practice nurses in diagnosing COPD patients. Firstly, Bunker et al (2009)10 assessed the effectiveness, feasibility and acceptability of COPD case finding by practice nurses performing spirometry on patients identified as being at risk of developing COPD. Practice nurses were trained in spirometry. 1010 patients from four general practices were identified who were aged 40-80 years and current or ex-smokers. Four hundred were randomised to receive a written invitation to attend a case finding appointment with the practice nurse, including spirometry. Seventy-nine patients attended, 16 (20.3% of attendees) had COPD diagnosed on spirometry; practice nurses correctly identified 10 of the 16, but also incorrectly identified a further six patients as having COPD. One patient in the usual care group was diagnosed with COPD, but this was not confirmed on spirometry. This study confirmed that COPD was underdiagnosed, with 20% of those at risk and attending for screening having COPD. The strategy successfully identified patients at risk, though the investigators conclude that further training in spirometry would be required for practice nurses to increase the accuracy of the diagnoses. The acceptability to patients of this method is not assessed.

Bunker, Reddel et al (2012)11 also report a trial protocol to assess early intervention for COPD by practice nurse-general practitioner teams, noting increasing involvement of practice nurses in delivering chronic care as part of a more structured chronic disease management in primary care. They use a pragmatic cluster randomised trial to test the hypothesis that intervention by a practice nurse-general practitioner team leads to improved health-related quality of life and greater adherence with clinical practice guidelines for patients with newly-diagnosed COPD, compared with usual care. While only a protocol is available, 40 general practices in greater metropolitan Sydney Australia will be recruited to identify patients at risk of COPD and invite them to attend a case finding appointment. Practices will be randomised to deliver either practice nurse-GP partnership care, or usual care, to patients newly-diagnosed with COPD. The active intervention will involve the practice nurse and GP working in partnership with the patient in developing and implementing a care plan involving smoking cessation, immunisation, pulmonary rehabilitation, medication review, assessment and correction of inhaler technique, nutritional advice, management of psycho-social issues, patient education, and management of co-morbidities. The primary outcome measure is health-related quality of life, assessed with the St George's Respiratory Questionnaire 12 months after diagnosis. Secondary outcome measures include validated disease-specific and general health related quality of life measures, smoking and immunisation status, medications, inhaler technique, and lung function. Outcomes will be assessed by project officers blinded to patients' randomization groups. The study will use proven case-finding methods to identify patients with undiagnosed COPD in general practice, where improved care has the potential for substantial benefit in health and healthcare utilisation.

10 Bunker J, Hermiz O, Zwar N, Dennis SM, Vagholkar S, Crockett A, Marks G. Feasibility and efficacy of COPD case finding by practice nurses. Australian family physician 2009; 38(10): 826-30. See also Cochrane Collaboration: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/clcentral/articles/627/CN- 00731627/frame.html 11 Bunker JM , Reddel HK , Dennis SM , Middleton S , VanSchayck C and Crockett AJ. Implementation science, 2012, 7, 83. See also Cochrane Collaboration: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/clcentral/articles/942/CN-00839942/frame.html

A Japanese study (Kida, Wakabayashi, et al, 2006)12 assessed the utility of a pre-interview questionnaire as a method for alerting both clinicians and patients with COPD. To screen subjects who might have COPD, the investigators developed an efficient pre-interview 11-item questionnaire (11-Q questionnaire) to alert primary care providers to the possibility of COPD, and the validity of this questionnaire was investigated. A subsequent study, a randomized and prospective cross-sectional study, was performed on a total of 245 subjects with or without respiratory symptoms. Good test- retest reliability and validity were shown in the first study. The second study showed that the 11-Q in COPD patients with more than moderate severity was significantly higher than that in bronchial asthma or non-cardiopulmonary subjects. Among the COPD patients, the total score significantly distinguished the severity of COPD as mild or more than moderate. The investigators concluded that the pre-interview questionnaire, 11-Q, was found to be a useful, simple, and inexpensive tool to alert primary care providers to subjects with COPD and could also be used to distinguish COPD with a more than moderate severity from bronchial asthma.

The only critically appraised economic evaluation was for comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis13.The study assessed the cost‐ effectiveness of two different screening programmes (case‐finding versus open spirometry) for the diagnosis of COPD. The authors concluded that the case‐finding programme using trained physicians was more cost‐effective for identifying new COPD cases. The intervention was a case‐finding programme providing spirometry to high‐risk subjects selected by a network of primary care physicians during their daily practice. All network physicians attended two two‐hour training sessions on the diagnosis and management of COPD. The comparator was an open spirometry programme based on public invitation, which involved local adverts offering spirometry free of charge to all subjects with chronic respiratory symptoms (such as cough, sputum production, wheezing of dyspnoea). All participants were older than 30 years and lived near 24 primary health care practices in a semi-rural area in Greece. The open programme identified 905 participants with acceptable spirometry, compared with 201 participants identified in the case‐finding programme. The case‐ finding programme diagnosed 36.3% of participants (73 out of 201) with COPD. The open programme diagnosed 10.8% of participants (98 out of 905) with COPD (OR 4.69, 95% CI 3.29 to 6.70). The proportion of new cases of COPD (after removing patients with previous COPD diagnoses) was 27.9% in the case‐finding programme compared with 8.4% in the open group (Odds Ratio (OR) 4.21, 95% CI 2.86 to 6.21).

The authors concluded that the case‐finding programme using trained physicians was more cost‐ effective for identifying new COPD cases, stating that the modest cost of approximately EUR 100 per new diagnosis of COPD had to be considered against the extreme costs of advanced disease, which may be avoided through early intervention. A thorough full economic evaluation would be needed to estimate the long‐term outcomes, both health and health‐care costs, from the different screening programmes for the population targeted. The Centre for Reviews and Dissemination concluded that

12 Kida K, Wakabayashi R, Mizuuchi T, Murata A. Screening for suspected chronic obstructive pulmonary disease with an eleven-item pre-interview questionnaire (11-Q). Internal medicine (Tokyo, Japan) 2006; 45(21): 1201-7. 13 Konstantikaki V, Kostikas K, Minas M, Batavanis G, Daniil Z, Gourgoulianis KI, Hatzoglou C. Comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis. Respiratory Medicine.2011;105(2):274‐281; Centre for Reviews and Dissemination. NHS Economic Evaluation Database (NHSEED) 2014 Issue 2: Comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis (Structured abstract) (see: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/cleed/articles/NHSEED-22011000258/frame.html)

16 the outcomes of the study were inappropriate to measure the cost‐effectiveness of the different screening programmes and that the authors' conclusions should be used with caution.

Conclusions

COPD is the most common chronic lung disease in the world, with mounting health burdens and costs. Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively unproductive effort as treatments other than smoking-cessation efforts were unlikely to alter its course. However, there is strong evidence to indicate that the majority of patients with objective COPD are not aware of their condition, contributing to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment. Novel methods of diagnostic testing - including alternative diagnostic strategies that may augment traditional spirometry - and primary-care provider health programmes focusing on nurse practitioners hold promise with respect to early diagnosis.

3.1.2 Lung Cancer

Lung cancer is one of the commonest fatal malignant diseases, causing over 37,000 deaths annually in the UK. Early detection and diagnosis is widely regarded as urgent for an effective treatment strategy for lung cancer and is key to reducing mortality. Patient prognosis in lung cancer largely depends on early diagnosis. The Cochrane Library identifies 25 studies (23 in ‘Trials’ and 2 in ‘Other Reviews’) meeting the criteria of ‘early diagnosis’ and ‘lung cancer’. Most of these reports relate to novel methods of diagnostic testing. One example was found of a rapid access lung cancer service (the lung investigation day). The UK lags behind many European countries in terms of cancer survival with a 5- year survival rate of only 5%. Concern has been expressed about inequalities in patient access to oncology services related to geographical location and age of patients, advanced disease at the time of presentation, and a lack of standardised care pathways. Multiprofessional teamwork has been found to improve coordination and patient support and reduce delays in diagnosis and treatment. As a result of inordinate delays in treatment planning, borderline resectable tumours at presentation may become unresectable. Initiatives to address these problems have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have only recently been studied (Banks, Hollinghurst et al, 2014).

Introduction of a lung investigation day on the operation of a rapid access clinic

There are few examples of rapid access lung cancer services. Papworth Hospital, Cambridge, has offered a tertiary diagnostic service that has been described in the literature. The Heart of England NHS Foundation Trust in Birmingham set up a multidisciplinary working group to review the diagnostic journey of patients attending rapid access lung cancer clinics, with the aim of rationalising this journey, reducing waiting times, and improving the patient experience. Different models of service reorganisation were discussed14. Patients with clinical or radiological features suspicious of

14 Rajasekaran AB, Silvey D, Leung B, Honeybourne D, Cayton RM, Reynolds J, and Trotter S. Effect of a multidisciplinary lung investigation day on a rapid access lung cancer service. Postgraduate Medical Journal 2006; 82: 414-416.

17 lung cancer are referred to the rapid access clinic by the general practitioner or radiologists. After initial clinical evaluation by a respiratory physician, appropriate patients are given information about the lung investigation day, which normally takes place within three working days of the rapid access clinic visit. The instigation of a multidisciplinary lung investigation day in this Birmingham trust was associated with significant reductions in the number of patients requiring bronchoscopy and in the time from presentation at the rapid access clinic to both histological diagnosis and presentation to the multidisciplinary team meeting. Prompt access to radiology and pathology services is key to the success of rapid access cancer services: the lung investigation day introduced dedicated computed topography (CT) and CT biopsy slots on fixed days in the radiology department and the agreement with the pathologists to fast track the reporting on samples, aiding the success of the care pathway. The lung cancer specialist nurses undertook to meet and support patients throughout the investigation day. The instigation of this innovation did not incur additional costs and new staff or facilities were not required.

Novel methods of diagnostic testing

There is very limited data (because of language of publication) on two systematic reviews cited in the Database of Abstracts of Reviews of Effects: ‘The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review’15 and ‘Diagnostic value of white light bronchoscopy combined with autofluorescence bronchoscopy for early diagnosis of lung cancer: a systematic review’16. The wider literature indicates that these new innovative technologies are effective.

Amongst the trials, Song, Liu et al (2011)17 report a prospective study to find the possible value of the combined use of four popular tumour markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung. Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumour group according to post- operative histological examinations. Serum levels of four tumour markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1, and neuron specific enolase (NSE) were assayed for each patient. When a combination of these four tumour markers - SCC, CEA, Cyfra 21-1 and NSE - were employed, the diagnosis power was strengthened, the investigators concluding that this approach is valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.

Yang, Wang, et al (2008)18 seek to determine the feasibility of detecting lung cancer in asymptomatic individuals with a high risk for lung cancer with low-radiation-dose spiral CT (LDCT) plus detection of p16 gene methylation in serum. A total of 523 participants were randomized to receive either a

15 Chang CY, Chang SJ, Chang SC, Yuan MK. The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review. Clinical Respiratory Journal.2013;7(1):1‐6; Cochrane Library: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/cldare/articles/DARE- 12013022848/frame.html. 16 Zhang W, Yang WL, Yang SY, Huo SF, Shang WL, Du J, Lin XL, Bu LN. Diagnostic value of white light bronchoscopy combined with autofluorescence bronchoscopy for early diagnosis of lung cancer: a systematic review. Journal of Xi'an Jiaotong University (Medical Sciences).2011;32(6):733‐738; Cochrane Library: http://onlinelibrary.wiley.com.chain.kent.ac.uk/o/cochrane/cldare/articles/DARE-12011007619/frame.html 17 Song W-A, Liu X, Tian X-D, Wang W, Liang C-Y, Zhang T, Guo J-T, Peng Y-H, Zhou NK. Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: A prospective study from China. Chinese Medical Journal 2011; 124(20); 3244-8. 18 Yang M, Wang J, Meng L-J, Wang Y, Xu L, Liu F-Y, Fan W-F. Analysis of feasibility of lung cancer screening with low-radiation-dose spiral CT scan plus detection of p16 gene methylation in serum. Chinese Journal of Cancer Prevention and Treatment 2008; 15(1):8-10.

18 screening LDCT scan plus p16 gene methylation detection (262 participants) or screening posteroanterior view chest radiograph (CRX) (261 participants). The inclusion criteria were male sex, age 55-75, smoking history of more than 20 packs every year, either a current cigarette smoker or a former smoker who had quit within the previous 10 years. The screens were completed on 96.6% (253/262) of subjects in the LDCT-p16 group and 93.5% (244/261) of subjects in the CRX group. A total of 10.7% (27/253) of screened subjects in the LDCT-p16 group and 6.6% (16/244) of those in the CRX group had findings that were suspicious for lung cancer. Four lung cancer patients in subjects in the LDCT-p16 group and one lung cancer patient in the CRX group were diagnosed following a positive screening result. The investigators conclude that it is a sensitive, safe and feasible method in screening early lung cancer with LDCT scan plus detection of p16 gene methylation in serum which can be used in screening early lung cancer instead of chest radiography.

Another Chinese study, Li, Chen et al, 201319, have examined elevated levels of survivin and livin mRNA (two members of the inhibitor of apoptosis gene family) in bronchial aspirates as markers to support the diagnosis of lung cancer. The aim of the study was to evaluate the diagnostic role of survivin and livin mRNA expression in the bronchial aspirates of patients with lung cancer. 70 lung cancer patients and 26 benign lung disease patients participated in the study. Survivin and livin mRNA were determined by reverse transcriptase-polymerase chain reaction. Survivin and livin mRNA levels in patients with lung cancer were significantly higher than in those with benign lung disease (p < 0.001 and p = 0.001, respectively). In lung cancer patients, specimens taken from cancerous bronchi had significantly higher levels of survivin and livin mRNA than specimens from the mirror side bronchi in the same patients (p < 0.001 and p = 0.001, respectively). The survivin mRNA expression in bronchial aspirates had sensitivity and specificity of 83 and 96% for diagnosis of lung cancer. Livin mRNA detection in bronchial aspirates showed 63% sensitivity and 92% specificity. The investigators conclude that survivin and livin mRNA detection in bronchial aspirates may be valuable diagnostic marker for the early diagnosis of lung cancer.

The aim of a study by Carozzi, Bisanzi et al (2010) was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening program with low-dose computed tomography (CT). Subjects enrolled in the baseline screening round of the trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worthy of further investigation20.

Ehmann, Boedeker et al (2012)21 have considered canine scent detection in the diagnosis of lung cancer through the exhaled breath of patients. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were employed. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or

19 Li J, Chen P, Li X-Q, Bao Q-L, Dai C-H, Ge L-P. Elevated levels of survivin and livin mRNA in bronchial aspirates as markers to support the diagnosis of lung cancer. International Journal of Cancer 2013; 132(5): 1098-104. 20 Carozzi FM, Bisanzi S, Falini P, Sani C, Venturini G, Lopes Pegna A, Bianchi R, Ronchi C, Picozzi G, Mascalchi M, Carrozzi L, Baliva F, Pistelli F, Tavanti L, Falaschi F, Grazzini M, Innocenti F, Paci E, ITALUNG Study Research group. Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis. Lung cancer (Amsterdam, Netherlands) 2010; 68(2): 216-21. 21 Ehmann R, Boedeker E, Friedrich U, Sagert J, Dippon J, Friedel G, Walles T. Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon. The European respiratory journal 2012; 39(3); 669-676.

19 chronic COPD) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. The investigators therefore assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer and that research efforts are required to engineer a clinically applicable screening tool.

Screening

Evidence reviews indicate that smokers have negative attitudes to screening and participation in lung cancer screening trials is poor (less than one in six of those eligible). To better understand attitudes to participation in a lung cancer screening trial (which is likely to predict uptake in screening programmes) a qualitative study of people accepting and declining participation in the Lung- SEARCH screening trial was conducted by Patel, Akporobaro, et al (2012)22. Two research questions were posed: Are the screening methods offered acceptable to patients? Why do some people take part and others decline? The qualitative study used semi-structured interviews with 60 respondents from three groups: (a) trial participants providing an annual sputum sample; (b) trial participants with a sputum sample showing abnormal cytology and thus undergoing annual CT scanning and bronchoscopy; and (c) those declining trial participation. Most respondents (48/60, 80%) viewed sputum provision, CT scanning and bronchoscopy as largely acceptable. Those declining trial participation described fear of bronchoscopy, inconvenience of travelling to hospitals for screening investigations, and perceived themselves as having low susceptibility to lung cancer or being too old to benefit. Patients declining participation discounted their risk from smoking and considered negative family histories and good health to be protective. Within those declining four typological behaviours were evident: 'too old to be bothered', 'worriers', 'fatalists' and 'avoiders'. The investigators concluded that sputum provision, CT scanning and bronchoscopy were largely acceptable to those participating in a screening trial. The decision to participate or decline reflects a complex balance of factors including acceptability and convenience of screening methods, risk perception, altruism and self- interest. These are issues that providers will need to address to improve uptake of lung cancer screening.

There are now a substantial number of studies that have investigated computed tomography (CT) screening for lung cancer. The New York Early Lung Cancer Action Project (ELCAP) has demonstrated that earlier diagnosis of lung cancer can be achieved with CT, resulting in considerable demand for CT screening23. The benefit of screening is that it provides for lung cancer treatment at a relatively early stage, leading to better outcomes than when treatment is prompted by symptoms and/or signs. There are counter-arguments, notably, that of ‘overdiagnosis’ (when screening finds lesions that are not life threatening, leading to unnecessary surgery). These conflicting claims led to a call for a randomized, controlled trial comparing CT screening with no screening, using a mortality endpoint. To this end, the National Lung Screening Trial (NLST) was set up, comparing CT screening with chest X-ray screening but requiring a 10-year timespan. While there have been inconsistencies in the subsequent reporting of ELCAP outcomes, the publication of the randomized US NLST shows a benefit of CT compared with chest x-ray screening. The NLST recently reported that CT lung cancer

22 Patel D, Akporobaro A, Chinyanganya N, Hackshaw A, Seale C, Spiro SG, Griffiths C. Attitudes to participation in a lung cancer screening trial: A qualitative study. Thorax 2012; 67(5): 418-25. 23 Henschke CI, Yankelevitz DF, Kostis WJ. CT screening for lung cancer. Seminars in ultrasound, CT, and MR 2q003; 24(1): 23-32.

20 screening, when applied to high-risk individuals (aged 55–74 years and with at least 30 pack-years of smoking and if quit, did so within 15 years), is associated with a 20% reduction in lung cancer mortality compared with chest x-ray screening24.

However, a systematic review of screening and early diagnosis using radiography (x-rays) and/or sputum cytology (examination of cells in sputum produced by coughing) for asymptomatic men at high risk of lung cancer concluded that it was not effective. Three randomised controlled trials (RCTs) including 30,000 male smokers over the age of 45, controlled prospective studies, and case- control studies found no evidence to suggest that screening can reduce lung cancer mortality25.

Preferences for cancer investigation

Related to this study is Banks, Hollinghurst et al (2014) study of preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees. In a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between December 2011 and August 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer was identified.

Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette. 3469 participants completed 6930 vignettes, 3052 individuals (88%) opting for investigation in their first vignette. No strong evidence was found that participants were more likely to opt for investigation with higher risks (although this association was strong when colorectal cancer was analysed alone). In multivariable analysis, age had an effect in all three cancer models: participants aged 60-69 years were significantly more likely to opt for investigation than were those aged 40-59 years, and those aged 70 years or older were less likely. Also associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers). Thus, participants expressed a clear preference for diagnostic testing at all risk levels. This willingness should be considered during design of cancer pathways in primary care and provides evidence for involvement of patients in referral decision making.

3.1.3 Asthma

Current good practice in diagnosis

The NICE Clinical Knowledge Summary (CKS) represents the current ‘best practice’ and is based on a 2011 British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society. The initial step is to decide how likely it is that the patient has asthma. For children, this decision is based on recognizing features that increase or decrease the probability of asthma. Features that increase the probability of asthma in children include: i) More than one of the following symptoms: wheeze, cough, difficulty breathing, chest tightness. Such symptoms particularly indicate asthma if they: are frequent and recurrent; are

24 PB Back. Inconsistencies in findings from the early lung cancer action project studies of lung cancer screening. JNCI J National Cancer Institute 2011; 103(13): 1002-1006. 25 Centre for Reviews and Dissemination. Management of lung cancer. Effective Health Care 1998;4(3).

21 worse at night and in the early morning; occur in response to, or are worse after, exercise or other triggers such as exposure to pets, cold or damp air, or with emotions or laughter; and occur even when the person has not got a cold (coryzal illness); ii) Personal history of another atopic disorder (hayfever, eczema); iii) Family history of asthma and/or atopic disorder; iv) widespread wheeze (bilateral, predominantly expiratory), the absence of which does not rule out asthma. In severe cases, chest wall movement may be reduced on both sides, and wheeze may not be audible; v) Prolonged expiration; and vi) Increased respiratory rate.

Features that lower the probability of asthma in children include: i) Symptoms with colds (coryzal illness) only; ii) Isolated cough in the absence of wheeze or difficulty breathing; iii) History of moist cough; iv) Prominent dizziness, light-headedness, peripheral tingling; v) Clinical features pointing to an alternative diagnosis; and repeatedly normal physical examination of the chest when symptomatic.

For adults, this decision is based on recognizing features that increase or decrease the probability of asthma and spirometry. Features that increase the probability of asthma in adults include: i) More than one of the following symptoms: wheeze, breathlessness, chest tightness, and cough, particularly if they: are worse at night and in the early morning; occur in response to exercise, allergen exposure, and cold air, and occur after taking aspirin or beta-blockers; ii) History of atopic disorder; iii) Family history of asthma and/or atopic disorder; iv) widespread wheeze (bilateral, predominantly expiratory), though absence of wheeze does not rule out asthma. In severe cases, chest wall movement may be reduced on both sides, and wheeze may not be audible; v) Prolonged expiration; and vi) Increased respiratory rate.

Features that lower the probability of asthma in adults include: i) Prominent dizziness, lightheadedness, peripheral tingling; ii) Chronic productive cough in the absence of wheeze or breathlessness; iii) Voice disturbance; iv) Symptoms with colds only; v) Significant smoking history (greater than 20 pack-years); vi) Cardiac disease; vii) Repeatedly normal physical examination of the chest when symptomatic; vii) Clinical features of an alternative diagnosis.

Clinical judgement is then used to categorize the person (child or adult) into one of three groups: High probability (diagnosis of asthma likely); Intermediate probability (diagnosis uncertain and insufficient evidence at first consultation to make a firm diagnosis, but no features to support an alternative diagnosis); and Low probability (diagnosis other than asthma likely).

For people with an intermediate and high probability of asthma, the person should be managed as suspected asthma (to confirm or refute the diagnosis). For people with a low probability of asthma an alternative diagnosis should be considered. Occupational asthma is diagnosed when the diagnosis of asthma is confirmed, the relationship between asthma and work exposure is made, and a specific cause is identified. Exercise-induced asthma is usually diagnosed based on symptoms related to exercise. People with exercise-induced asthma report symptoms such as coughing and wheezing after 5–10 minutes of exercise or for up to 1–2 hours after finishing exercise. The symptoms are generally worse when breathing cold or dry air (outdoors), or with longer duration or higher intensity of exercise.

Spirometry plays a key role in diagnosis and is the preferred method to demonstrate airway obstruction because: it more clearly identifies airway obstruction than peak expiratory flow (PEF), and the results are less dependent on effort; PEF variability can be increased in people with conditions commonly confused with asthma; PEF should only be used if spirometry is unavailable; and in view

22 of the potential requirement for treatment over many years, it is important to obtain objective support for the diagnosis of asthma.

Spirometry should be performed on all adults to assess for the presence and severity of airway obstruction, which is confirmed when forced expiratory volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio is less than 0.7. Whether or not spirometry should happen before starting treatment depends on the certainty of the initial diagnosis and the severity of the presenting symptoms. Normal spirometry obtained when a person is asymptomatic does not exclude a diagnosis of asthma and repeated assessment and measurement may be necessary.

Spirometry is recommended for children with an intermediate probability of asthma if they are able to perform the test (usually older than 5 years). Spirographs require calibration to allow accurate interpretation of the results (for example Rosenthal normal values based on the child's sex and height). Health care professionals require training on how to calibrate and interpret the results from a spirogram. CKS recommend that advice should be sought regarding carrying out spirometry in children and interpreting the results, unless the healthcare professional has received the appropriate training. Measuring lung function in young children is difficult and not usually possible in children under 5 years of age. Normal results obtained when the child is asymptomatic do not exclude a diagnosis of asthma.

Early diagnosis

Asthma is often unrecognised and untreated as its clinical features are non-specific and pulmonary function tests may be insensitive. Early diagnosis is particularly important in children and the literature on early diagnosis relates mainly to young children. Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children: the majority of children with recurrent asthma-like symptoms are symptom free at 6 years and do not have asthma. One study reports that while approximately 40% of children wheeze in their first year of life, only 30% of pre-schoolers with recurrent wheezing still have asthma at the age of 6 years. With the conventional diagnostic tools it is not easy to differentiate between preschool children with transient symptoms and children with asthma. Currently there is the risk of over-treatment of children with transient wheeze and under-treatment of children with asthma. To capture literature on early diagnosis searches were undertaken using keywords “early diagnosis” and “asthma” on the Cochrane Library databases. In addition 410 abstracts identified using these keywords on PubMed were reviewed.

The literature on reasons for diagnostic delay in childhood asthma is limited. One qualitative study26 seeks to identify these reasons and to develop tools for early diagnosis. Using semi-structured interviews with the parents of 30 children with asthma aged 2-15 years, combined with 15 GP interviews, the study found that asthma symptoms for most of the children started during their first year. The typical symptom pattern reported by parents consisted of insidious recurrent or continuous respiratory symptoms, particularly bad at night, often lasting several weeks or months, provoked or aggravated by common colds or foggy weather. In describing the symptoms, parents focussed on coughing and sputum production. The children's asthmatic diagnosis was obscured by excessive diagnostic emphasis on respiratory infections. The typical reasons for diagnostic delay seemed to be that doctors did not pay enough attention to the history of recurrent cough and unspecified respiratory symptoms. Further, some doctors relied more on the present symptoms and physical examination,

26 Østergaard MS. Childhood asthma: reasons for diagnostic delay and facilitation of early diagnosis--a qualitative study. Prim Care Respir J. 2005 Feb;14(1):25-30.

23 although asthmatic patients may have normal auscultation on examination. Several doctors did not expect asthma in infancy. Earlier diagnosis and treatment may result from adapting to a new diagnostic concept for asthma, which highlights a history of periodic or chronic cough, wheeze and/or breathing difficulties and the typical asthma pattern in toddlers.

Delays in diagnosing asthma in children are common and are known to delay asthma-specific treatment. Moreover, children with undiagnosed asthmatic symptoms account for much illness and hospitalisation. However, few studies have investigated whether a delay in asthma diagnosis affects the use of health care services. One study27 - a retrospective cohort study with subjects elicited from a convenience sample of 839 healthy children - was designed to assess whether a delay in diagnosis of asthma influenced the use of health care services. The criteria for asthma was met in 276 (33%) subjects, of whom 179 (65%) had a delay in the diagnosis of asthma and 97 (35%) had a timely diagnosis. Data on health care services (e.g., flu shot, availability of a peak flow meter, hospitalisations, and urgent care or emergency department visits) and the frequency of systemic steroid treatments were collected from medical records during the first 18 years of life. Children with a delay in asthma diagnosis were more likely to visit urgent care centres at least once (40.8% versus 21.6%; p < 0.001), compared with those with a timely diagnosis. There were no significant differences in other health care service or systemic steroid use. Thus, a delay in the diagnosis of asthma was associated with an increase in urgent care visits suggesting suboptimal health care services.

Interventions to increase early diagnosis

The interventions are a mix of biomedical approaches (use of biomarkers), counselling, and techniques to improve the accuracy of diagnosis.

There is an extensive literature on biomarkers. Further development is acknowledged as needed for efficient treatment and early diagnosis. Recently, several airway inflammatory biomarkers have emerged as valuable tools in diagnosis and management of asthma, the analysis of which has provided promising and non-invasive techniques that facilitate the detection of disease phenotypes as well as measurement of therapeutic efficacy. Conventional treatments do not adequately control some severe cases of asthma. Novel therapeutic agents have been developed to target various biomarkers involved in the inflammatory responses and have been investigated in patients with asthma. Fatemi, Sadroddiny et al (2014)28 summarize the most studied asthma biomarkers, derived from a variety of biological sources including exhaled gases, induced sputum, serum and urine. van de Kant, Klaassen et al (2009)29 specifically address early diagnosis by using non-invasive biomarkers of airway inflammation and early lung function measurements. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children.

27 Lynch BA, Van Norman CA, Jacobson RM, Weaver AL, Juhn YJ. Impact of delay in asthma diagnosis on health care service use. Allergy Asthma Proc. 2010 Jul-Aug;31(4):e48-e52. 28 Fatemi F, Sadroddiny E, Gheibi A, Mohammadi Farsani T, Kardar GA. Biomolecular markers in assessment and treatment of asthma. Respirology. 2014 May;19(4):514-23. See also: Bloemen K, Van Den Heuvel R, Govarts E, Hooyberghs J, Nelen V, Witters E, Desager K, Schoeters G. A new approach to study exhaled proteins as potential biomarkers for asthma. Clin Exp Allergy. 2011 Mar;41(3):346-56. 29 van de Kant KD, Klaassen EM, Jöbsis Q, Nijhuis AJ, van Schayck OC, Dompeling E. Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study. BMC Public Health 2009; 9: 2010.

The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. The investigators indicate they have initiated a prospective case-control study in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure) on the basis of lung function assessments and current respiratory symptoms ('golden standard'). From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate), blood and faeces are performed. As this is only a study protocol, no results are reported.

Hafkamp-de Groen, Mohangoo, et al (2010)30 evaluates the effectiveness of early detection of preschool children with asthma symptoms, followed by a counselling intervention at preventive child health centres. Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years. A cluster randomised controlled trial was embedded in the Rotterdam population-based prospective cohort study ‘Generation R’ in which 7893 children (born between April 2002 and January 2006) participated in the postnatal phase. Sixteen child health centres are involved, randomised into eight intervention and eight control centres. Since June 2005, an early detection tool has been applied at age 14, 24, 36 and 45 months at the intervention centres. Children who met the intervention criteria received counselling intervention (personal advice to parents to prevent smoke exposure of the child, and/or referral to the general practitioner or asthma nurse). The primary outcome was asthma diagnosis at age 6 years. Secondary outcomes included frequency and severity of asthma symptoms, health-related quality of life, fractional exhaled nitric oxide and airway resistance at age 6 years. Analysis was according to the intention-to-treat principle. This is a protocol with data collection reported to be completed at the end of 2011.

Given that early and correct diagnosis of asthma in wheezing children is essential for early treatment and prevention of under- or over-treatment, Schönberger, van Schayck, et al (2004)31 investigate whether combining frequency and age of onset of wheezing illness with respiratory and atopic morbidity at age 0-6 years and sociodemographic parameters for asthma might be useful for the general practitioner to diagnose asthma early and accurately. A birth cohort was used with mean follow-up 20 years in general practice. The outcome, adolescent asthma, was analysed in relation to wheezing and non-wheezing respiratory and personal and familial atopic morbidity. 1586 (64%) of the children could be followed. Adolescent asthma occurred in 6.4%. There were indications for under- and over-diagnosis of asthma at age 0-6 years. Non-recurrent wheezing (only one episode) and recurrent wheezing (>or =2 episodes) in the first three years of life, and recurrent wheezing at age 4-6 increased the risk with odds ratios (95% confidence interval) of 3.3 (1.9-5.6), 4.7 (2.8-8.2) and 15.4 (7.1-33.7), respectively. The risk additionally increased independently with a family history for asthma, (2.0 [1.1-3.6]), atopic dermatitis (1.7 [1.1-2.7]) and sinusitis (2.9 [1.3-6.4]) and decreased for > or =2nd born children (0.38 [0.19-0.47]) and those with a low social-economic status (0.61 [0.39-

30 Hafkamp-de Groen E, Mohangoo AD, de Jongste JC, van der Wouden JC, Moll HA, Jaddoe VW, Hofman A, de Koning HJ, Raat H. Early detection and counselling intervention of asthma symptoms in preschool children: study design of a cluster randomised controlled trial. BMC Public Health 2010;10: 555. 31 Schönberger H, van Schayck O, Muris J, Bor H, van den Hoogen H, Knottnerus A, van Weel C. Towards improving the accuracy of diagnosing asthma in early childhood. Eur J Gen Pract. 2004 Dec;10(4):138-45, 151.

0.94]). The investigators conclude that easily available history and clinical data may facilitate the early diagnosis of asthma in children with wheezing illness.

Another study aimed to validate optimal action points in written action plans for early detection of asthma exacerbations32. The investigators analysed daily symptoms and morning peak expiratory flows (PEFs) from two previous studies. Potential action points were based on analysis of symptom scores (standard deviations) percentage of personal best PEF, PEF variability in relation to a run-in period or combinations of these measures. Sensitivity and specificity for predicting exacerbations were obtained for each action point. The numbers needed to treat to prevent one exacerbation and the time interval between reaching action point criteria and the start of the exacerbation were calculated. Based on these parameters, the optimal action points for symptoms, PEF and PEF plus symptoms were determined, and their performance compared with published guidelines' action points. The optimal action points were, for symptoms, statistical variability (standard deviations) and, for PEF, <70% of personal best. The combination of PEF plus symptoms performed best, with improved specificity and earlier detection. The main benefits associated with using these action points was to reduce false positive rates for detecting exacerbations. The investigators concluded that early detection of asthma exacerbations can be improved using a composite action point comprising symptoms and PEF measurements over 1 week.

Finally, approaches to early diagnosis of asthma in pre-school children have included the use of an Asthma Predictive Index (API) that assists in determining at early age which infant/preschoolers will go on to develop asthma33. This was developed to help predict which child would develop persistent (life-long) asthma, and which would seem to ‘outgrow’ it. Most wheezing during the first three years of life is related to viral respiratory infections, such as respiratory syncytial virus (RSV). Respiratory viruses and symptoms of early asthma may be hard to distinguish from each other, making diagnosis and treatment problematic. The 2007 National Heart, Lung and Blood Institute (NHLBI) Guidelines for the Diagnosis and Management of Asthma describes the API, a guide to determining which small children will likely have asthma in later years.

High-risk children (under age three) who have had four or more wheezing episodes in the past year that lasted more than one day, and affected sleep, are much more likely to have persistent (i.e., life- long) asthma after the age of five, if they have either of the following: One major criteria amongst: Parent with asthma; Physician diagnosis of atopic dermatitis (eczema); and evidence of sensitization to allergens in the air (i.e., positive skin tests or blood tests to allergens such as trees, grasses, weeds, molds, or dust mites) or two minor criteria amongst: Evidence of food allergies; 4 percent or more blood eosinophilia (increased numbers of white blood cells called eosinophils are made by the body to fight off allergic disease. They can collect in tissues and cause damage to the airways of the lung); and wheezing apart from colds.

The API was developed after following almost a thousand children through 13 years of age. Seventy- six (76%) of children diagnosed with asthma after six years of age (considered persistent or life-long asthma) had a positive API before three years of age. Ninety-seven (97%) of children who did not have asthma after six years of age had a negative API before 3 years of age. This data indicates offers a strong argument for use of the API routinely in young children.

32 Honkoop PJ, Taylor DR, Smith AD, Snoeck-Stroband JB, Sont JK. Early detection of asthma exacerbations by using action points in self-management plans. Eur Respir J. 2013 Jan;41(1):53-9. 33 Castro-Rodriguez JA. The Asthma Predictive Index: early diagnosis of asthma. Curr Opin Allergy Clin Immunol. 2011 Jun;11(3):157-61.

3.1.4 Obesity

Obesity is a term used to describe somebody who is very overweight and it is increasingly common in the UK, estimated to affect around one in every four adults and around one in every five children aged 10 to 11 in the UK. The most common method for defining obesity is body mass index (BMI).

BMI is a measure of whether a person’s weight for their height is healthy. For most adults a BMI of 25 to 29.9 means a person is considered overweight; a BMI of 30 to 39.9 means a person is obese; and a BMI of 40 or above means a person is considered severely obese. BMI is not used to definitively diagnose obesity – as people who are very muscular sometimes have a high BMI, without excess fat. However, for most people, BMI can be a useful indication of whether they may be overweight. A better measure of excess fat is waist circumference, and can be used as an additional measure in people who are overweight (with a BMI of 25 to 29.9) or moderately obese (with a BMI of 30 to 34.9). Generally, men with a waist circumference of 94cm or more and women with a waist circumference of 80cm or more are more likely to develop obesity-related health problems.

NICE classifies adults as overweight or obese using their BMI: Overweight — BMI of 25– 29.9 kg/m2; Obesity l — BMI of 30–34.9 kg/m2; Obesity ll — BMI of 35–39.9 kg/m2; and Obesity lll — BMI of greater than or equal to 40 kg/m2. It adds that BMI should be interpreted with caution in very muscular adults, or in people with atrophy as it is a less accurate measure of adiposity in these groups. The basis for this recommendation is the NICE guideline Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children (NICE 2006).

Obesity can cause shortness of breath as extra weight in the chest and abdomen increases the work the muscles that control breathing must do. Both patients and clinicians report that breathlessness is a relatively common symptom for obese people. Epidemiological data show that about 50% of obese patients are breathless and up to 70% of obese elderly complain of some degree of breathlessness. IMPRESS have calculated that typically a GP would have 285 obese patients on his/her list. Of them, 140 would also report breathlessness. Among the breathless patients, about 114 would have obesity as the reason for breathlessness. However, IMPRESS has noted that the Royal College of Physicians Action on Obesity report has only one mention of breathlessness and no discussion of it. In adults, obesity is normally accompanied by complications or comorbidities. The most important are type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease because of their clinical burden and the associated risk of premature death.

There is a paucity of literature on the early diagnosis of obesity, except in children where there is a focus on candidate biomarkers34.

3.1.5 Patient experience

Since the literature on early diagnosis interventions accorded only limited importance to patient experience, searches for reports of patient experiences of diagnosis were undertaken on Medline and other literature databases and DIPEx (Database of Individual Patient Experiences). The NHS Patient Experience Surveys were also reviewed. Studies were found for COPD, lung cancer, and asthma but were sparse for other conditions for which breathlessness is a symptom.

34 Hulsmans M, Holvoet P. MicroRNAs as early biomarkers in obesity and related metabolic and cardiovascular diseases. Curr Pharm Des. 2013;19(32):5704-17.

COPD

Data on patient experience amongst those diagnosed with COPD is limited. The Royal College of Physicians is developing a one year project that will involve identifying, exploring and piloting patient-reported experience measures (PREM) tools and methodologies and will consider the practicalities/feasibility of collecting PREM data in primary care, secondary care and pulmonary rehabilitation. The PREM workstream will engage patients through focus group activities and will result in a report to the Healthcare Quality Improvement Partnership (HQIP) in July 2014 to inform decisions regarding the potential integration of PREMs into the national COPD audit programme.

However, the Royal College of Physicians has funded one study that has been published. The North East London, North Central London and Essex (NECLES) Health Innovation and Education Cluster (HIEC) in association with the Royal College of Physicians, British Thoracic Society, British Lung Foundation, Picker Institute, City University and Anglia Ruskin University collaborated in the development of a PREM for use in all COPD patients35. The experiences of 64 patients with COPD across the community of the NECLES region, with a range of severity and presentation, and 19 patients with recent hospitalisation due to COPD related conditions were captured. Amongst the categories the community patient group experience focused on was ‘journey to diagnosis’. The journey to diagnosis was varied among patients, some indicating that it was a gradual onset of repeated chest infections over a number of years that finally resulted in being diagnosed with COPD, while for others a significant infection had resulted in hospitalisation leading to their diagnosis. Some patients reported having been diagnosed with respiratory conditions such as asthma, bronchiectasis, and emphysema leading up to the diagnosis of COPD. A few had tuberculosis in the past and others mentioned pneumonia. Physical limitations on exertion were symptoms that resulted in some patients seeking medical attention leading to their diagnosis of COPD. The affective responses to the journey to diagnosis revealed considerable concern. The affective response of ‘frightened’ primarily related to patients’ experiencing physical limitations and uncertainty of what they were caused by: ‘On a couple of occasions I had to run for the bus and I thought I was having a heart attack…. It frightened me’ and recognition of what the diagnosis meant: ‘I was afraid I would end up like....’. The affective response of frustration was primarily around getting a definitive diagnosis for their symptoms: ‘I kept seeing the GP and was getting frustrated…. Eventually I saw a Dr who said go for a Chest X-Ray (which led to diagnosis)…’. The affective response of surprise/shock attended the diagnosis of COPD itself for some patients who considered they were fit or without any symptoms: ‘For someone who was always physically fit…’.

A UK team of investigators have developed a questionnaire to assess patient-reported experience measures in patients with COPD attending a hospital outpatient clinic, notably, to assess whether the processes necessary to improve outcomes in COPD had been dealt with in the clinic and understood by the patient and also the understanding of COPD by the patient and whether they were satisfied with the consultation36. The questionnaire was completed by 142 new and follow up patients. Although results are limited on early diagnosis, the investigators found that 92% of patients had spirometry performed at their visit but fewer (78%) had the results explained. Before the consultation 57% of

35 Andrew S, Walker S. Developing a Patient Reported Experience Measure for Chronic Obstructive Pulmonary Disease (PREM-COPD). Final Report. 2012 (February). Accessed at: https://www.brit- thoracic.org.uk/document-library/clinical-information/copd/developing-a-patient-reported-experience-measure- copd/ 36 Powrie DJ, AliM, Ansari S, Lingam KG, Mulley P, Hope S, Davison AG. Assessing the Patient Experience of COPD Care Using an Ipsos MORI Questionnaire as a Patient Reported Experience Measure (PREM). Thorax 2012; 67: A101.

28 patients thought they had a good understanding, 30% moderate and 13% little or no understanding of their condition: afterwards these improved only somewhat to 67%, 23% and 10% respectively. 29% believed that their knowledge of how to reduce exacerbations had increased after the consultation. 87% of patients thought that the average 20 minutes length of the review was about right and 85% were satisfied overall with the consultation.

Lung cancer

The Cancer Reform Strategy (CRS) has identified the early diagnosis of cancers as a critical issue and the second Annual Report on the CRS states that ‘patients in this country are diagnosed later and with more advanced disease than elsewhere in Europe’37. Some measure of patient experience with respect to the early diagnosis of lung cancer is available from the NHS Cancer Patient Experience survey for 2013. One of the question sets in the survey was designed to identify the views of patients about seeing their GP prior to referral to hospital and the length of time that elapsed.

Of those cancer patients who saw their GP before going to hospital, 74% said that they saw their GP either once (53%) or twice (21%) before they were told they needed to go to hospital about the health problem caused by cancer (the same percentage as in the 2012 cancer patient experience survey). 17% saw their GP 3 or 4 times, and 9% saw their GP 5 or more times. 20% said they did not see their GP before going to hospital. There was a significant variation across tumour sites in the proportion of patients saying they saw their GP only once or twice before being referred on to a cancer specialist – 68% in case of lung cancer, below the average for all cancers. There were also significant variations across NHS trusts - 55-94% - in the proportion of patients saying they saw their GP only once or twice before being referred on to a cancer specialist.

84% of patients (for all cancers) said they felt that they were seen as soon as they thought was necessary: 10% felt they should have been seen a bit sooner and a further 7% felt they should have been seen a lot sooner. The proportion for lung cancer was 84%, the same as the average for all cancers. Scores in Trusts (for all cancers) ranged from 67% to 95%, the highest Trust score. 79% of patients said that the gap between the time when they first thought something might be wrong and when they first saw a hospital doctor was less than 3 months. 11% said the gap was 3-6 months; 4% said 6-12 months and 4% said more than 12 months.

These findings indicate that around a quarter of patients saw their GP only once or twice before they were told they needed to go to hospital about the health problem caused by cancer and a fifth said that they did not see their GP. Moreover, a significant proportion of patients said that they felt they should have been seen sooner by their GPs.

Asthma

The literature on patients’ experience of the diagnosis of asthma is sparse. However, a NICE consultation on draft guidance recommending three non-invasive tests help diagnose and treat asthma - that measure the concentration of nitric oxide in a person's breath (levels of this gas are higher in people with asthma than other people) - cites some evidence for patient experience38. Carole Longson, NICE Health Technology Evaluation Centre Director, states: ‘An accurate diagnosis of asthma is

37 Cancer Reform Strategy Second Annual Report, December 2009 Gateway Ref. 12927 NHS England. Cancer Patient Experience Survey 2013. National Report. Public Health England: Leeds, August 2013.

38 https://www.nice.org.uk/News/Press-and-Media/nice-consults-on-draft-guidance-recommending-tests-to- help-diagnose-and-treat-asthma

29 often very complicated and can sometimes take many years. That can mean that treatments can be less than optimal - for example, the use of corticosteroids in people whose condition doesn't respond to this drug - and this can have a direct impact on a person's health. However, given the complexities of diagnosing asthma, which is based on both symptoms and response to treatment, the Committee considered that FeNO39 testing used on its own would not be able to replace current practice for diagnosis. The Committee concluded that FeNO testing improved the accuracy of diagnosis when used in addition to other tests to diagnose the condition’. The Committee heard from a patient expert that FeNO-guided management could result in the patients better understanding their own disease and disease progression and make them more willing to accept the need for anti-inflammatory treatment to control their asthma. This could help avoid hospitalisation because of exacerbations and improve patient experience.

39 The amount of forced exhaled nitric oxide in the breath.

3.2 The ‘rapid access clinic’ model

The specification for this scoping study asks what evidence, evaluation and/or models there are for diagnosis of disease from a symptom-based perspective and what models, standards, guidelines or good practice already exists for ‘rapid’ access to diagnostics generally, such as Rapid Access Chest Pain Clinics? Since most of the rapid access clinics are focussed on symptoms, it seemed appropriate to treat these topics together.

Following the recommendation in the National Service Framework (NSF) for Coronary Heart Disease (2000) to provide specialist assessment within two weeks of GP referral, the rapid access chest pain clinic was widely adopted across England. While the main focus of these clinics is to improve patient access to cardiology services in particular, their relevance as a ‘rapid access model’ is wider than this main function. Studies of some of these clinics provide information on all diagnoses related to the symptom of ‘chest pain’. Moreover, there are relevant findings with regard to organisation, equity of access, substitutability, and referral mechanisms. Other rapid access clinics have followed for symptoms related to cardiac and other conditions.

The literature searches have revealed that there are a number of models for diagnosis of disease from a symptom-based perspective. The range of symptoms that have been the focus of rapid access models and/or dedicated diagnostic pathways include:

. Chest pain . Atrial fibrillation . Blackouts . Palpitations . Breathlessness . Murmur

There are, in addition, other symptom-based approaches, including:

. Lumps and bumps40 . Unexplained weight loss . Unexplained bleeding . Fatigue

Not all of these additional symptoms have seen a focus on related rapid access clinics and they are less relevant to diseases related to breathlessness as a symptom. For these reasons, they are not further considered. Similarly, some rapid access clinics have focused on specific diseases, such as prostate cancer. These are also excluded from the scope of the review. Breathlessness will be considered in chapter 4.

3.2.1 Rapid access chest pain clinics (RACPCs)

Background

Management options for patients with new onset chest pain comprise presentation to the general practitioner or direct attendance at the Accident and Emergency (A and E) department. Depending on clinical presentation / urgency, the management options of the GP may include referral to secondary

40 See, for example, ‘Rapid Access to a One Stop Neck Lump Clinic’. Accessed at: http://ebookbrowsee.net/hillingdon-gp-neck-lump-presentation-pdf-d327090517.

31 care, either directly to the local A and E department or to a cardiology outpatient clinic. Alternatively, the GP may directly request additional diagnostic tests such as a resting electrocardiogram (ECG) or an exercise stress test (ETT), where they have direct access to these facilities, before deciding whether to refer the patient to secondary care or to supervise continuing management in the primary care setting. However, referral to an emergency department may be viewed as unjustified for non-acute symptoms. Moreover, waiting lists for outpatient appointments can result in diagnostic delay in patients with possible coronary artery disease and further outpatient visits are usually needed to have investigations performed. Further, the resting ECG may have a limited role in diagnosing angina. While open access ETT is regarded as a useful method of confirming suspected coronary artery disease, around 80% of GPs do not feel sufficiently confident to interpret the results of an ETT. Diagnosing coronary artery disease in the GP surgery can be difficult if the patient presents with non- specific / vague symptoms or if the disease is silent. In one study (Newby, Fox, Flint, Boon, 199841) only about one third of diagnoses of chest pain made in general practice were concordant with the diagnoses made in secondary care where a range of diagnostic measures in addition to specialist experience were available.

In the emergency department setting, one study (Emerson, Russell, Wyatt, Crichton, Pantin, Morgan et al, 1989)42 reported inappropriate discharge of 11.8% of patients with acute ischaemic chest pain who presented to the emergency department. Further, many patients with atypical chest pain are unnecessarily admitted to hospital. To overcome the limitations of these referral pathways, rapid access assessment units have been developed in the UK, involving specialist (cardiologist) assessment of chest pain to facilitate the early diagnosis of angina and grading of its severity.

Rapid access chest pain clinics (RACPCs) in the UK date back to 1976 and were first established to support epidemiological research (Duncan, Fulton, Morrison, Lutz, Donald, Kerr et al, 197643; Gandhi, Lampe, Wood, 199544). They focus primarily on ambulatory chest pain patients and their potential to improve cardiac services was recognised and acknowledged in the NSF for Coronary Heart Disease (CHD) (Department of Health, 2000) - the blueprint for action to reduce the incidence of CHD – published in March 2000. The NSF gave official backing and a financial boost to RACPCs and designated them as the service model of choice. The initial priority was to establish 50 RACPCs by April 2001, another 50 by April 2002 and with a nationwide rollout thereafter. The rollout was more rapid than planned and, by January 2003, there were more than 175 such clinics. By 2004, nearly every acute trust in the UK had an RACPC (The National Service Framework for Coronary Heart Disease, 200445).

The potential of RACPCs is to provide quick, efficient communication between primary and secondary care and to facilitate rapid assessment of patients with symptoms suggestive of new onset angina by a cardiologist. In the words of the NSF, the RACPC is a service primarily ‘to help ensure that people who develop new symptoms that their GP thinks might be due to angina can be assessed

41 Newby DE, Fox KA, Flint LL, Boon NA. 1998. A 'same day' direct-access chest pain clinic: improved management and reduced hospitalization. Qjm.91(5):333-7. 42 Emerson PA, Russell NJ, Wyatt J, Crichton N, Pantin CF, Morgan AD et al. 1989. An audit of doctor's management of patients with chest pain in the accident and emergency department. Quarterly Journal of Medicine.70(263):213-20. 43 Duncan B, Fulton M, Morrison SL, Lutz W, Donald KW, Kerr F et al. 1976. Prognosis of new and worsening angina pectoris. British Medical Journal.1(6016):981-5. 44 Gandhi MM, Lampe FC, Wood DA. 1995. Incidence, clinical characteristics, and short-term prognosis of angina pectoris. British Heart Journal.73(2): 193-8. 45 Department of Health. 2000. National Service Framework for Coronary Heart Disease: modern standards and service models. London: DoH.

32 by a specialist within two weeks of referral’ (Department of Health, 2000). They are a type of outpatient clinic and do not encourage referral of patients with suspected myocardial infarction or unstable angina which require emergency treatment and hospital admission. The RACPC has a number of aims (Timmis et al, 2006)46: i) to establish rapid ‘same-day’ referral and discharge policy. If not ‘same-day’ then to ensure that the waiting time for appointment does not exceed the set ‘14 day’ target. ii) To provide a diagnosis with risk stratification, treatment and follow up plan. iii) By implication, optimising the use of hospitalisation for appropriate patients, for example, those with acute coronary syndromes.

Rapid access chest pain assessment clinics in the USA have had a rather different history. They were developed as part of a strategy to reduce mortality and morbidity from myocardial infarction through rapid thrombolysis and the reduction of the rate of inappropriate discharges of missed acute myocardial infarction from the emergency department. However, management shifted to patients with less acute coronary syndromes who were still at significant risk of adverse outcomes when discharged and the diagnosis and treatment of stable chest pain syndromes. This subset of patients may or may not have angina and may present with typical, atypical, or non-diagnostic symptoms. As in the UK these chest pain assessment centres (CPACs) have proliferated, reaching over 1200 by 2006.

Advantages and disadvantages of RACPCs

There are a number of potential advantages of RACPCs (Timmis et al, 2006):

. RACPCs provide a specialist cardiology opinion to help identify patients with coronary artery disease and their categorisation into three groups: at high risk who may need immediate hospitalisation, those with intermediate risk who may not need to be admitted, but require outpatient treatment, and those at low risk of having significant coronary artery disease who may benefit from general lifestyle advice, and therapy to modify reversible risk factors. By implication, RACPCs reduce hospitalisation of patients with non-cardiac chest pain and provide re-assurance for them (Davie et al, 1998)47. . These clinics provide a good setting for initiation of secondary prevention with drug therapies: aspirin, statins, angiotensin enzyme inhibitors, beta-blockers. . The RACPC ‘one-stop’ element is especially helpful for older patients or those with reduced mobility, who may find it difficult to undertake repeat visits to the hospital. Such clinics also help prevent administrative and communication delays. . Maintenance of computerised databases facilitates audit and research, ensures uniformity of approach in assessment of patients and improves communication between primary and secondary care (Ray et al, 199848).

With respect to implementing breathlessness clinics, relevant advantages include the facilitation of risk stratification; reduction in inappropriate referrals to hospital out-patient and in-patient departments; the ‘one-stop’ element that minimises repeat hospital visits for the elderly and people

46 Timmis A,, Sekhri N, Feder G, Hemingway H. Are Rapid Access Chest Pain Clinics effective and fair? Characteristics and outcomes of patients from six centres. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R and D (CCSDO). May 2006. 47 Davie AP, Caesar D, Caruana L, Clegg G, Spiller J, Capewell S et al. 1998. Outcome from a rapid-assessment chest pain clinic. Qjm.91(5):339-43.

48 Ray S, Archbold RA, Preston S, Ranjadayalan K, Suliman A, Timmis AD. 1998. Computer-generated correspondence for patients attending an open-access chest pain clinic. Journal of the Royal College of Physicians of London. 32(5): 420-1.

33 with reduced mobility (that also makes such service more affordable and convenient with respect to travel); and the availability of standardised information on assessment in computerised databases.

Amongst potential disadvantages of RACPCs:

. Patients with acute coronary syndromes may be referred, causing potential delay in their emergency management. . There is potential for inappropriate referrals of patients with other cardiac disorders such as arrhythmias and valve abnormalities, of patients with clinically obvious non-cardiac chest pain. The service may be seen as a shortcut for an expert opinion to avoid long outpatient waiting lists, especially for patients already diagnosed with coronary artery disease. The RACPCs do not have the resources to provide these patients with the rapid medical attention they need.

Thus, the key finding for the establishment of breathlessness clinics is the risk of inappropriate referrals, though this may be less given the aims of breathlessness clinics.

Key findings of the literature

There are two major studies of RACPCs on the NIHR journal library databases. Firstly, ‘Are Rapid Chest Pain Clinics effective and fair? Characteristics and outcomes of patients from six centres’, was undertaken for the National Co-ordinating Centre for NHS Service Delivery and Organisation R and D (NCCSDO)49. A systematic review on the evidence for rapid access chest pain clinics was also identified (Mant, McManus, Oakes, Delaney, Barton, Deeks et al, 2004)50. Timmis et al (2006) citation tracked key papers and identified ten studies (all more descriptive than evaluative in focus).

Clinic set-up

These ten tracked studies had recruited 90 to 1001 patients for assessment of chest pain and all confirmed the feasibility of the RACPC to outpatient care. The set-up of these clinics varied according to the available resources and were staffed by either cardiologists or cardiology registrars. All but two of these clinics saw patients within 24 hours of referral (other than weekends or bank holidays). One saw patients by appointment but had difficulty keeping to the 14-day target (McGavigan, Begley, Moncrieff, Hogg, Dunn, 2003)51 and the other (Byrne, Murdoch, Morrison, McMurray, 200252) audited attendances at both a weekly and a daily clinic. The daily clinic had more referrals for patients with acute coronary symptoms and those with low risk/non-coronary chest pain compared with the weekly clinic, which had more patients with stable coronary diseases referred to it, although referral guidelines were similar. All clinics discouraged referral of patients with suspected

49 ID: 08/1210/032. Chief Investigator: Dr Adam Timmis. Organisation: Newham University Hospital NHS Trust. Year: 2006. Report: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0006/64446/FR-08-1210-032.pdf 50 Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care. Authors: Mant J, McManus RJ, Oakes RA, Delaney BC, Barton PM, Deeks JJ, Hammersley L, Davies RC, Davies MK, Hobbs FD. Journal: Health Technology Assessment Year: 2004; Volume: 8 Issue: 2. 51 McGavigan A D, Begley P E, Moncrieff J, Hogg K J, Dunn FG. 2003. Rapid Access Chest Pain Clinics - Can they be Justified? Scottish Medical Journal 48(1), 13-16. 52 Byrne J, Murdoch D, Morrison C, McMurray J. 2002. An audit of activity and outcome from a daily and a weekly 'one stop' rapid assessment chest pain clinic. Postgraduate Journal of Medicine. 78:43-6.

34 acute coronary syndrome except for one (Norell, Lythall, Coghlan, Cheng, Kushwaha, Swan et al, 199253) where the exclusion criteria were not clearly specified.

Diagnostic tests

A resting 12 lead ECG was undertaken on all patients but the rate of exercise stress testing (ETT) varied, from 7 to 58 percent depending on the group of patients being studied. In one study, for example, ETT was performed on all possible patients with angina (Ghandi, Lampe, Wood, 199554). However, another exercised patients only if there was a doubt in diagnosis (Duncan, Fulton, Morrison, Lutz, Donald, Kerr et al, 197655). Four studies made comparison with control groups (Newby, Fox, Flint, Boon, 199856; McGavigan, Begley, Moncrieff, Hogg, Dunn, 200357; el Gaylani, Weston, Shandall, Penny, Buchalter, 199758; O’Toole and Channer, 199559) none of which was randomised.

Importance of early diagnosis

All these studies emphasised the importance of treatment strategies for angina patients being introduced promptly, as most adverse events (CHD related death, non-fatal myocardial infarction (MI)) occur within six months of diagnosis (Duncan, Fulton, Morrison, Lutz, Donald, Kerr et al, 197660; Ghandi, Lampe, Wood, 199561; Davie, Caesar, Caruana, Clegg, Spiller, Capewell et al, 199862).

Reduction of avoidable admissions

Two studies (Newby, Fox, Flint, Boon, 199863; el Gaylani, Weston, Shandall, Penny, Buchalter, 199764) suggested that these clinics may reduce unnecessary admissions, comparing the clinic diagnosis with the respective GP’s hypothetical plan for further management had the clinic not

53 Norell M, Lythall D, Coghlan G, Cheng A, Kushwaha S, Swan J et al. 1992. Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic. British Heart Journal. 67(1): 53-6. 54 Gandhi MM, Lampe FC, Wood DA. 1995. Incidence, clinical characteristics, and short-term prognosis of angina pectoris. British Heart Journal.73(2): 193-8. 55 Duncan B, Fulton M, Morrison SL, Lutz W, Donald KW, Kerr F et al. 1976. Prognosis of new and worsening angina pectoris. British Medical Journal.1(6016):981-5. 56 Newby DE, Fox KA, Flint LL, Boon NA. 1998. A 'same day' direct-access chest pain clinic: improved management and reduced hospitalization. Qjm.91(5):333-7. 57 McGavigan A D, Begley P E, Moncrieff J, Hogg K J, Dunn FG. 2003. Rapid Access Chest Pain Clinics - Can they be Justified? Scottish Medical Journal 48(1), 13-16. 58 el Gaylani N, Weston CF, Shandall A, Penny WJ, Buchalter. 1997. Experience of a rapid access acute chest pain clinic. Irish Medical Journal.90(4):139-40. 59 O' Toole L, and Channer KS. 1995. Direct access exercise electrocardiography: a new service that improves the management of suspected ischaemic heart disease in the community. British Heart Journal 73, 200. 60 Duncan B, Fulton M, Morrison SL, Lutz W, Donald KW, Kerr F et al. 1976. Prognosis of new and worsening angina pectoris. British Medical Journal.1(6016):981-5. 61 Gandhi MM, Lampe FC, Wood DA. 1995. Incidence, clinical characteristics, and short-term prognosis of angina pectoris. British Heart Journal.73(2): 193-8. 62 Davie AP, Caesar D, Caruana L, Clegg G, Spiller J, Capewell S et al. 1998. Outcome from a rapid-assessment chest pain clinic. Qjm.91(5):339-43. 63 Newby DE, Fox KA, Flint LL, Boon NA. 1998. A 'same day' direct-access chest pain clinic: improved management and reduced hospitalization. Qjm.91(5):333-7. 64 el Gaylani N, Weston CF, Shandall A, Penny WJ, Buchalter. 1997. Experience of a rapid access acute chest pain clinic. Irish Medical Journal.90(4):139-40.

35 existed. Only four studies provided follow-up data but numbers were small, follow-up short (6 to16 months), and in two studies recruitment was restricted.

Gaps in the evidence base i) Little is known about the contemporary prognosis of stable angina or non-cardiac chest pain, in the setting of RACPCs. Timmis et al (1996) have stated: ‘… we do not know the reliability of a single specialist assessment of patients with chest pain to distinguish between those whose pain is due to significant heart disease and those who have another cause, not requiring further cardiological management’. Past studies had low event rates and insufficient power to test the differences in outcomes between different groups of patients. Data are from drug trials based on secondary and tertiary care population is prone to selection bias. Some studies have suggested that patients with non- cardiac chest pain may not have as benign an outcome as is commonly believed, raising concern about the outcome of patients diagnosed with non-cardiac chest pain in one-stop clinics (where 60 to 70 per cent of patients have this diagnosis).

While these clinics have rapidly proliferated, Timmis et al argue that the assumption that RACPCs effectively distinguish between cardiac and non-cardiac origins of chest pain allowing early identification and management of high-risk patients has not been tested. Similarly, Mant et al (Mant, McManus, Oakes, Delaney, Barton, Deeks et al, 2004) state that there was little evidence in the available literature about the impact of RACPCs for reducing inappropriate hospital admissions with chest pain and in a broader sense about the effectiveness of these clinics (no data being available prior to the introduction of the RACPC). Until they undertook their study, Timmis et al state that there are not enough data to assess the effect of RACPCs on already stretched revascularisation services and routine cardiology outpatient work.

ii) A second identified gap in health service provision is equity of access to the RACPC services, which is needed if outcomes are to be optimal. A range of studies (e.g. Chaturvedi, Rai, Shlomo, 199765; Dong, Shlomo, Colhoun, Chaturvedi, 199866; Richards, Reid, Watt, 200267) have shown that inequities exist with reduced access to cardiac services for some ethnic minority groups, women and older people. Patient barriers to access may include language, culture, socio-economic status, and health seeking behaviour. One study found that older people had low expectations of treatment, were less informed about the latest advances, feared hospitals and saw doctors as busy (Gardner, Chapple, Green, 199968). Barakat, Wells, Ramdhany, Mills, Timmis, 200369, showed that both Bangladeshi and white patients recognised symptoms of MI and attended the emergency department (ED) in time, but initiation of treatment was delayed in the ethnic group who had more atypical features. Socio- economic status has long been known as a confounder for coronary artery disease. However, as at 2004 there had been no information about the ability of RACPCs to deliver appropriate and equitable

65 Chaturvedi N, Rai H, Ben Shlomo Y. 1997. Lay diagnosis and health-care-seeking behaviour for chest pain in south Asians and Europeans. Lancet;350:1578-83. 66 Dong W, Ben Shlomo Y, Colhoun H, Chaturvedi N. 1998. Gender differences in accessing cardiac surgery across England: a cross-sectional analysis of the health survey for England. Social Sciences and Medicine 47:1773-80. 67 Richards HM, Reid ME, Watt GCM. 2002. Socioeconomic variations in responses to chest pain: qualitative study. BMJ 324: 1308. 68 Gardner K, Chapple A, Green J. 1999. Barriers to referral in patients with angina: qualitative study and commentary: Generalisability and validity in qualitative research. BMJ 319:418-21. 69 Barakat K, Wells Z, Ramdhany S, Mills PG, Timmis AD. 2003. Bangladeshi patients present with non-classic features of acute myocardial infarction and are treated less aggressively in east London, UK. Heart 89:276-9.

36 investigation and treatment in vulnerable groups, especially those with poor socio-economic status, females, some ethnic groups, and older people.

Timmis et al analyse their cohort to address the gaps: the outstanding questions about the effectiveness of RACPCs regarding prognosis, equity of access by age, gender, ethnicity, and socio- economic status, impact on other cardiology outpatient services, and differences in models of care. In this multi-centre cohort study registry data was drawn from six RACPCs across the country, including Newham, established in 1996 and the service model for the NSF: registry data on a total of 11,082 consecutive patients (448 visits) attending RACPCs was available for the period 1996-2002. The four explicit aims of the study are:

. To determine whether RACPCs are appropriately targeted towards patients with chest pain of cardiac origin; . To analyse populations using RACPCs, equity of access to the clinics and subsequent cardiac procedures (exercise stress tests and coronary angiography) and their appropriateness; . To compare different models of care across the participating centres; . To determine whether RACPC act in addition to, or as a substitute for, other services.

Are RACPCs appropriately targeted towards patients with chest pain of cardiac origin?

The assumption that one-stop assessment in RACPCs can successfully separate patients with stable chest pain into those with and without angina was unproven and the extent to which the differential diagnosis accurately predicted risk was unknown. The investigators concluded that RACPCs effectively identify patients at increased coronary risk (those with previously undiagnosed angina, uncomplicated by prior myocardial infarction) but fail to correctly diagnose all patients. Thus, there is a need to improve the diagnosis and treatment of ambulatory patients when they first present with chest pain in order to reduce mortality rates in this high-risk group. While multiple factors contribute to the hazard of adverse outcomes in patients with angina, symptoms for >4 weeks increased this hazard, reinforcing the need for rapid assessment of the patient with chest pain. The added hazard of adverse outcomes for patients with an abnormal ECG justifies the routine recordings obtained in all patients attending RACPCs.

Analysis of populations using RACPCs, equity of access to the clinics, and referral for subsequent cardiac procedures and their appropriateness

Diagnostic categories and outcomes were found to vary systematically with demographic characteristics. Centres were found to vary in relation to diagnosis; management and outcomes; referral criteria; local management policy; frequency of clinics; and local availability of cardiac investigations. The investigators found evidence for inequity of access to rapid access chest pain clinics for older people and those from more deprived areas, but none for women or South Asian patients.

A major purpose of rapid assessment of chest pain is that it should provide access to invasive investigation equitably for all patients in whom it is indicated, regardless of demographic characteristics, to prevent or postpone coronary events. The investigators found that among patients attending RACPCs, there were significant inequities in referrals for coronary angiography for older people, women, south Asians, and those from more deprived wards.

Finally, the investigators look at appropriateness of cardiac investigation in RACPCs, especially overuse and under-use according to age, gender, ethnicity, and deprivation. They found considerable

37 under-use of ETT (electrocardiography while exercising on a treadmill) in RACPCs; under-use of coronary angiography was associated with adverse outcomes; there was inequity in the use of ETT for women, south Asians, and older patients; and under-use of coronary angiography was greater for older and south Asian patients.

Comparison of different models of care in RACPCs

The investigators found some heterogeneity in how models of care in different centres had evolved to meet local need. About half of RACPCs had been set up in response to the NSF for CHD. Around two-thirds (69%) had a computerised database, nearly all (97%) operated with an appointment system, just over half (53%) accepted referrals only from primary care, most provided a service 3-4 times a week seeing 15-16 patients per week, and around half (48%) saw patients within 14 days. Of the survey responders, around 60% were staffed solely by doctors, around a third (36%) by both doctors and nurses, and just 3% by nurses only. Doctors were responsible for making the final diagnosis in nearly all (93%) of RACPCs and referral for an angiogram (95%). Thus, there was wide variation in the configuration of RACPCs reflecting resource allocation and perceptions of local need.

Interviews with staff in the six participating RACPCs provide further information on waiting times and the role of doctors and nurses. Five of the RACPCs met the NSF waiting time target of <14 days for all referrals. Attendance rates for the six clinics plateaued after 3-4 months at a level that reflected the frequency with which clinics were held. Most of the clinics operated an appointment system: just one was open access and was much valued by patients, as there was no waiting time. Nurses participated in three of the clinics, in roles such as administration, history taking, diagnosis, and management decision making. However, the view that the doctor should be responsible for making the final diagnosis and management plan was unanimous. All the senior staff agreed that the RACPCs provided a good way to overcome delay in assessment of chest pain but were frustrated at the number of inappropriate referrals received even though clearly stated referral guidelines were in place. The investigators concluded that ‘no single model of care best serves the main purpose of RACPCs to see patients with undifferentiated chest pain within 14 days of referral and to diagnose and initiate appropriate treatment in those with angina (Timmins et al, 2006, p. 24).

Do RACPCs act in addition to or as a substitute for other services?

While the investigators indicate that RACPCs should substitute for existing services and reduce to zero referrals to outpatient cardiology clinics (OPCCs) who fulfil criteria, they state that it is not known if effective substitution has been achieved. They identified 1382 RACPC patients and 228 OPCC patients with new onset chest pain at Newham University Hospital. Angina was diagnosed in 26% of the OPCC group compared with 23% of the RACPC group. Mean waiting time for an OPCC appointment was 97 +/- 43 days. RACPC patients were seen the same day or first working day after the referral. Just 2% of the OPCC group had symptoms for <4 weeks when seen, compared with two- thirds (67%) of the RACPC group. Thus, there was substantial, but not complete, substitution for the OPCC. One important finding was the unexplained tendency for south Asians being referred to the OPCC.

Findings relevant to the establishment of diagnostic breathlessness clinics

The rationale for rapid access chest pain clinics lays in the high coronary event rates amongst patients with incident angina, justifying the priority for rapid assessment and the need for improved diagnosis

38 and treatment. Patients with symptoms that had started >4 weeks prior to attending the RACPC were at greater risk than their counterparts with more recent onset, underlining the importance of the NSF for CHD directive that all patients with recent onset chest pain should be seen within 2 weeks of referral by the specialist. The two main specific aims of RACPCs - rapid specialist assessment within a specified period of referral by the GP and a ‘one stop’ service providing diagnosis and risk stratification - are likely to be shared by diagnostic breathlessness clinics.

Diagnostic precision is crucial. Patients in the Timmins et al. cohort diagnosed with non-cardiac chest pain had a lower coronary event rate but still accounted for one third of all observed coronary deaths or non-fatal myocardial infarctions, even though they had been through a screening process for coronary disease. It is likely that most of these patients were misdiagnosed at the initial assessment, albeit amounting to a minority of cases. The investigators identify the need for research to identify methods for improving diagnostic precision, including non-invasive coronary imaging.

If the rapid adoption of breathlessness clinics results in variation in design, consideration needs to be given to the standardisation of data collection. Around only two-thirds of RACPCs had a computerised database. Computerised databases were found to facilitate the running of RACPCs, simplify the audit process (enabling feedback to primary care, thereby contributing to refinements of the service), standardise history taking and cardiac examination, and enable a core dataset to be collected for national audit. Indeed, Timmins et al argue that, though urgently needed, there are no large registry data of patients presenting with new onset chest pain and these investigators strongly recommend the establishment of a national clinical database of patients with new onset chest pain attending RACPCs.

If there is rapid proliferation, consideration needs to be given throughout this process to policy review and evaluation. The latter might include randomised controlled trials to address questions about clinical outcomes in patients attending breathlessness clinics or in navigating new pathways and effectiveness, with a comparative or control group for current service configurations / pathways.

Despite rapid proliferation, RACPCs still fail to correctly identify all patients at increased risk, so improvements in diagnosis and treatment are needed when they first present. However, long-term reviews of rapid access clinics for chest pain and arrhythmias do provide findings for a full range of diagnoses. Importantly for models for breathlessness clinics, such studies do show a diagnostic yield that has remained reasonably constant across all diagnostic categories. This suggests that these rapid access clinics are reasonably efficient in diagnosing a range of conditions for a particular symptom and that standardisation of diagnostic approaches has in all likelihood contributed to this constancy in diagnostic yield.

Equity of access to breathlessness clinics needs to be considered to ensure that they achieve optimal outcomes. When access to effective interventions is inequitable, groups with poorer access will have worse outcomes. This will require such access to be assessed for particular subgroups, such as the elderly, women, those from deprived areas, those disadvantaged by socio-economic status, and people from minority ethnic groups. Equity of access should include distance from new clinics. Inequities in referrals for further assessment or treatment also need to be addressed. The cohort study (Timmins et al, 2006) found evidence for inequity of access to rapid chest pain clinics for older people and those from more deprived areas, but not for women or south Asian patients. They found no evidence of inequity of use of exercise tolerance tests but south Asians, older people, and people from more deprived areas were less likely to be referred for coronary angiography.

Consideration would need to be given to the best skill-mix for breathlessness clinics, amongst doctors (consultants, senior house officers, specialist registrars, staff grades, associate specialists, and GPs with special interest) and nurses and distribution of functions. With respect to the RACPC model, the NSF did not specify staffing requirements, other than that the patient should be seen by a ‘specialist’. Timmins et al study revealed heterogeneity with regard to skill mix, including doctor-led, nurse-led, and hybrid doctor-nurse clinics. The choice has implications for costs, clinical management (including making the diagnosis), and continuity of care.

The RACPC model revealed a level of frustration concerning the high number of inappropriate referrals received despite clearly stated referral guidelines. Direct referral to the RACPC was regarded as vital for preventing administrative delay. An appointment system was favoured as it allowed better planning of workload and allowed vetting of referrals. Clear referral guidelines are needed - worked up in conjunction with primary care colleagues - that are strictly adhered to if referrals are to be appropriate and manageable. Survey data revealed that 53% of RACPCs accepted primary care referrals only, the remainder in-hospital referrals as well.

The frequency of days for breathlessness clinics can usefully be informed by the example of RACPCs. There was general consensus amongst informants that RACPCs should offer a daily service, though this was achieved in only two of the six studied. The lack of sufficient staff was an important reason for limiting the frequency of RACPCs. Open access RACPCs can operate successfully but require adequate staffing levels.

Finally, consideration needs to be taken of delays inherent in the referral process, including the time it takes for the symptomatic patient to seek medical attention. Timmins et al (2006) argue that more rapid assessment of patients with chest pain might require increasing levels of awareness among the general population about the significance of new onset chest pain. This chimes with Public Health England’s awareness campaign on breathlessness.

3.2.2 Rapid access clinics for arrhythmias, blackouts, palpitations, and murmur

The rationale for rapid access clinics for arrhythmias lays in the fact that diagnosis and care for arrhythmias is complex and diverse. Also, a key challenge is to establish more equal and more rapid access to heart rhythm care. As arrhythmias are differentiated, the type of heart rhythm problem determines the type of access, speed of access, and characteristics of evaluating clinical staff. The diagnosis of cardiac arrhythmias can be difficult in primary care and the waiting time for a first appointment with a consultant cardiologist can be long, sometimes several months. Palpitations, presyncope, and syncope are common symptoms that may be linked to serious tachyarrhythmias or bradycardias. Atrial fibrillation is by far the most common arrhythmia in the population with around one million people having the condition and can lead to a threefold increased risk of developing heart failure and a fivefold increased risk of stroke. People with atrial fibrillation have a mortality rate nearly double that of age and sex matched controls at every age and the condition is closely associated with stroke and heart failure. Moreover, it increases healthcare consumption by a factor of 10-20. Although there is substantial clinical evidence that warfarin is an effective prophylaxis for thromboembolism in these patients, oral anticoagulation remains suboptimal in both primary and secondary care, with treatment rates of only 21–50%.

A range of rapid access clinic models has been advocated to improve care for arrhythmias70, notably:

. Rapid Access Palpitations Clinics (RAPC) . Rapid Access Blackout Clinics (RABC) . Rapid Access Atrial Fibrillation Clinics (RAAFC)

More than one of the models may be encompassed in a generic Rapid Access Arrhythmia Clinic.

3.2.2.1 Rapid Access Palpitations Clinic

The evidence base for rapid access palpitations clinics is limited. There is a paucity of detailed descriptions, information on efficacy at diagnosing the underlying condition, follow-up studies, or cost-effectiveness evidence and no substantive reports have been found in the Cochrane Library, Database of Abstracts of Reviews of Effects (DARE), or PubMed. The rationale for these clinics lies in the fact that many of these patients have palpitations that trouble them but are unlikely to have an important arrhythmia. Moreover, patients with palpitations can take up a significant amount of GP time. Thus, early resolution to diagnosis is needed to detect illness that is more serious or to assure the patient and reduce needless anxiety. The objective of such clinics then is to establish whether the patient’s symptoms might indicate a dangerous arrhythmia because of the presence of underlying structural heart disease or a primary electrical abnormality of the heart and to reassure the patient and close the episode without further uncertainty for the patient and cost.

The Arrhythmia Alliance indicates that in this type of rapid access clinic, protocols will focus on assessment of risk by history, examination, and resting 12-Lead ECG, with echocardiography in some cases. This could be effectively undertaken by specialist nurses and cardiac technicians working with a supervising junior doctor and with a named consultant in overall charge of the clinic. Such clinics could be run alongside existing clinics to maximise efficiency (in much the way that device clinics run alongside consultant-lead outpatient clinics and run by technicians and nurses).

There are few examples of these clinics. An Electrophysiology Specialist Nurse at Central Manchester and Manchester Children's Foundation Trust leads a team of nurses managing electrophysiology / device patients and assesses patients in a Nurse-led Rapid Access Palpitations Clinic and Rapid Access Blackout Clinic Setting. A Rapid Access Palpitation Clinic has been established at Bart’s and the London NHS Trust. A Consultant Cardiologist / Electrophysiologist at the Regional Cardiac Centre, Wythenshawe Hospital-University Hospital of South Manchester, is the lead electrophysiologist for the rapid access palpitation clinic and open access atrial fibrillation clinic. A One Stop Rapid Access Palpitation Clinic at Euxton Hall Hospital, Chorley, provides assessment by a Consultant Cardiologist as well as a 12 lead ECG and a 24-hour ECG recording71. It also offers a second assessment phase of echocardiography and exercise testing for patients who need these additional tests. The Rapid Access Palpitation Clinic examines patients as soon as they are referred by their GP and enables quick diagnosis and treatment.

Only one detailed descriptive study72 has been identified. A prospective study investigates the role of a nurse-led clinic in the assessment of patients with palpitations in a UK district general hospital.

70 Arrhythmia Alliance. Establishing Rapid Access Clinics. Stratford-upon-Avon: Arrhythmia Alliance, April 2010. Accessed at: http://heartrhythmcharity.org.uk/www/media/files/Establishing%20Rapid%20Access%20Clinics.pdf. 71 http://www.davisheart.co.uk/images/One%20Stop%20Heart%20Palpitation.pdf 72 Scott PA, Appleford P, Farrell TG, Andrews NP. A nurse-led palpitations clinic: a 2-year experience. Postgraduate medical journal 86:1011 2010 Jan pp. 3-7.

Patients with palpitations are referred from primary care or the emergency department. Referral letters were screened, and only patients without high-risk features or a documented arrhythmia were diverted to the palpitations clinic. Patients were evaluated using a protocol. All patients had an ECG and ambulatory ECG monitoring and were discussed with a cardiologist.

Over 15 months, 389 patients were seen. The mean time from referral to assessment was 38 days (range 3-142). The most common diagnoses were symptomatic extrasystoles (42%) and sinus rhythm (22%). Significant arrhythmias were diagnosed in 15% (atrial fibrillation/flutter, 8%; supraventricular arrhythmias, 6%). Only 52 (13%) were subsequently referred to a cardiologist, including 20 with high-risk features. These 20 patients waited on average an additional 70 days to be seen by a cardiologist compared with patients who were seen directly by a cardiologist after referral by primary care or the emergency department. The investigators concluded that for low-risk patients, a nurse-led palpitations clinic might provide a viable alternative to the traditional cardiology outpatient service. However, as an unforeseen finding, some high-risk patients were seen despite attempts to exclude them and led to a clinically important delay in their appropriate assessment. Thus, before adopting a nurse-led palpitations service, a rigorous pathway for the early assessment of high-risk patients needs to be agreed.

3.2.2.2 Rapid Access Blackout Clinics (RABCs)

There is a strong rationale for such clinics. For example, syncopal events and falls represent a major healthcare and cost burden for the NHS, the cost of falls per annum in the NHS being estimated at over £1 billion. Each year between 35% of community living adults over 65 years and 45% of adults over 80 years have such an event and this common medical problem accounts for up to 6% of emergency medical admissions. The importance of rapid access blackout clinics is that they provide a comprehensive investigation pathway: as a diagnosis is elusive in up to 40% of cases the importance of making a correct diagnosis is clear (and the implications of an incorrect one)73. Even in those who do receive a diagnosis, this may be incorrect, especially in the older age group. With respect to the diagnosis of epilepsy, up to 100,000 people in the UK live with the moniker but without the condition. The prognostic implications for those suffering from syncope can be profound: Soteriades et al. (2002)74 evaluated the incidence and prognosis of syncope in participants in the Framingham Heart Study and found the most frequently identified causes were vasovagal syncope, cardiac syncope and orthostatic hypotension, though 36% still had no demonstrable cause. While there was no increased risk of cardiovascular morbidity or mortality associated with vasovagal syncope, persons who had a diagnosis of cardiac syncope or syncope of unknown cause were at increased risk of death from any cause in this study. Byrne and O’Shea (2009)75 argue that epidemiological data demonstrate an increasing prevalence of blackouts and falls with age (and that the incidence of injuries sustained in the fall increases dramatically with age), coupled with co-morbidities, dependency and dementia patients (a particularly frail group with an annual fall rate of 40–60%) makes this a priority area in healthcare.

Rapid access blackout clinics are wider than syncope clinics as blackouts can be caused by epilepsy, syncope and psychogenic causes. So effective rapid access blackout clinics require a multidisciplinary

73 Allcock LM, O’Shea D. Diagnostic yield and development of a neurocardiovascular investigation unit for older adults in a district hospital. J Gerontol A Biol Sci Med Sci 2000;55:M458–M462; Soteriades ES, Evans JC, Larson MG et al. Incidence and prognosis of syncope. N Engl J Med 2002;12:878–85. 74 Soteriades ES, Evans JC, Larson MG et al. Incidence and prognosis of syncope. N Engl J Med 2002;12:878– 85. 75 Byrne D, O’Shea D. Rapid access blackout clinics: a priority for the elderly. Br J Cardiol 2009;16(1):9–10

42 team comprising neurology (and epileptology where needed), cardiology (and electrophysiology where needed), psychology (and neuropsychology where needed), and care of the elderly. In planning and managing such clinics, advice and consultation are needed with colleagues in Emergency Medicine, Acute Medicine and Primary Care. However, the Arrhythmia Alliance acknowledges that rapid access blackout clinics have limitations. Some patients with simple fainting may be discharged back to their own GP, while others may be found to have a clear electrophysiological diagnosis and will need urgent onward referral. Some may be thought to have generalised epilepsy and will need neurological review at an early stage. Many patients who attend such a clinic, may, however, not be diagnosed. The Arrhythmia Alliance sees their value in providing patients and doctors with a readily available triage resource that should avoid the difficulties associated within expert clinical assessment, poor diagnostic tests, and a high rate of misdiagnosis and will be of particular value in triaging patients with blackouts of uncertain cause. This diagnostic approach was suggested by the European Society of Cardiology.

Only one evaluation of a rapid access blackouts triage clinic has been identified in the literature. The study by Petkar, Bell et al (2011)76, that describes such a clinic at Central Manchester Foundation Trust, claims to be ‘the first study of a multidisciplinary, specialist nurse-led rapid access blackouts triage clinic’. This clinic was set up following the 2005 NSF for Heart Disease guidelines and the 18- week commissioning pathway for blackouts. This approach was adopted to address the variable and delayed triage process for assessment of risk, testing for a diagnosis, and access to further specialised care. Doctors faced with uncertainty over diagnosis often resort to admission and patients may then wait to undergo unnecessary investigations. Convulsive syncope is frequently misdiagnosed as epilepsy. NICE guidance for epilepsy advises rapid access for ‘first fit’ patients. The NSF for Elderly Care prescribed rapid access to falls clinics, many having been shown to have syncope.

The aims of the clinic were to: provide a rapid clinical assessment and ECG within 2 weeks of referral; assess, and where possible, diagnose the cause of blackouts; triage patients into the high- and low-risk groups, and ensure rapid specialist assessment in high-risk patients where appropriate; help decrease hospitalisation of low-risk patients by providing a very short wait for assessment; and use of the clinical assessment to determine the cause of black-outs, then application of further tests and/or treatment (patients otherwise being promptly directed to the most appropriate specialist care).

Clinics were led by specialist nurses in arrhythmias, falls and epilepsy. Medical cover and ECG over reading were provided by an experienced cardiologist who determined the diagnosis and advised on treatment. Patients were encouraged to attend with an eyewitness and all had a 12-lead ECG performed. Patients then underwent a detailed assessment by one of three specialist nurses, using a structured electronic interview. Patients were stratified as high risk (red flag) and green flag.

327 patients participated in the study (307 of whom had suffered from blackouts). Referral to assessment took 35 +/- 19 days. Only 9% of patients were seen within 14 days of referral. The delays in assessment were due to lack of resources. Most referrals were from GPs (36%) and general physicians (31%). Most patients were diagnosed with syncope, usually reflex syncope (78.5%). A further 20% of patients had suffered blackouts but the cause was not clear from the triage, the profiling of risk being reported back to the GP. Very few patients had epilepsy. The investigators concluded that a rapid access blackout clinic such as the Manchester clinic can evaluate blackout patients fairly promptly and that many patients can be diagnosed and treated within the clinic without

76 Petkar S, Bell W, Rice N, Iddon P, Cooper P, McKee D, Curtis N, Hanley M, Stuart J, Mackway Jones K, Fitzpatrick AP. Initial experience with a rapid access blackouts triage clinic. Clinical Medicine 2011; 11 (1) 11- 16.

43 the need for onward specialist referral. Relatively few patients needed neurological referral. Both specialist nurses and a doctor experienced in ECG interpretation (not necessarily a cardiologist) were needed. The primary objective of the clinic was not to provide rapid access to the entire care pathway but to provide a step between the ‘first responder’ and ‘specialist care’ (as envisioned in the 18-week commissioning pathway). However, a primary objective is rapid triage to the right care pathway. The model successfully addressed the misdiagnosis of blackouts/transient loss of consciousness (T-LOC) as epilepsy, avoiding overreliance on more sophisticated investigations like electroencephalography, which have a low diagnostic yield. Echocardiography was carried out in 62% of patients and provided a further refinement of the assessment of risk, but was regarded as a not essential complimentary investigation in such a clinic. The devised risk stratification methods were compatible with the methods used to construct the 18-week commissioning pathway for blackouts.

4.2.2.3 Rapid access arrhythmia /atrial fibrillation clinics

The literature on rapid access arrhythmia clinics is more limited than that for rapid access chest pain clinics. A search on the Cochrane Library and NIHR journals library found no relevant studies but PubMed revealed one relevant paper on rapid access arrhythmia clinics for the diagnosis and management of new arrhythmias presenting in the community77. It is clear that this model has not been widely disseminated in the way chest pain clinics have. In the case of rapid access chest pain clinics the National Service Framework for Coronary Heart Disease advocated such clinics, which created a momentum for change in cardiological practice and the rapid adoption of this service model across the country.

The key paper on rapid access arrhythmia clinics is that by Martins, Fox et al (2004). These investigators had in 2000-01 reported their experience in setting up rapid access clinics for chest pain and heart failure and had proposed in various papers that this service should be extended to arrhythmias. They established a rapid access arrhythmias clinic in the cardiology department of Charing Cross Hospital in West London, a large undergraduate teaching hospital with secondary cardiology services serving an ethnically and socioeconomically diverse population of 150,000- 200,000, the aims of which were: i) to provide a rapid diagnosis of significant cardiac arrhythmias in patients presenting for the first time in the community; ii) to describe the clinical characteristics of incident cases of atrial fibrillation; and iii) to facilitate the early initiation of warfarin and other treatments for atrial fibrillation based on European Society of Cardiology guidelines.

The organisation of the clinic

All patients presenting to their general practitioner or to the emergency department with a first presentation of symptoms or signs suggestive of a cardiac arrhythmia were eligible for referral to this new service. Before the opening of the clinic, all general practitioners within the hospital’s catchment area were sent letters advertising this new service, building upon the already established rapid access chest pain clinic at the hospital. The service was also advertised during the induction programme of new senior house officers in the emergency department. The clinic was open each weekday between 9.30 am and 12.30 pm and no appointments were needed. All patients had an ECG followed by a clinical assessment by the doctor running the clinic. Those with a history of palpitations, presyncope, or syncope had a 24-hour Marquette Hellige Holter monitor system fitted the same day. All patients

77 J L Martins, K F Fox, D A Wood, D C Lefroy, T J Collier, N S Peters. Rapid access arrhythmia clinic for the diagnosis and management of new arrhythmias presenting in the community: a prospective, descriptive study. Heart 2004;90:877–881.

44 with confirmed atrial fibrillation also underwent chest radiography and transthoracic echocardiography, and were individually risk stratified as low, intermediate, or high risk for thromboembolism according to European Society of Cardiology guidelines. Low risk patients were aged less than 65 years without any high-risk features (previous thromboembolism, heart failure, hypertension, diabetes mellitus, left ventricular dysfunction, coronary heart disease) and were treated with aspirin or no antithrombotic. Warfarin was started for patients assessed as moderate to high risk for stroke (age greater than 65 years or less than 65 years with high risk features) provided there were no clinical contraindications. In cases where there was diagnostic difficulty, further investigations such as event (loop) recording or tilt testing were arranged. The initial diagnosis was based on the clinical assessment and ECG. The final diagnosis was made after reviewing the results of all further investigations. Patients with a cardiac arrhythmia that required hospital follow up were reviewed as cardiology outpatients or referred to a dedicated arrhythmia clinic led by a consultant electrophysiologist. All data were entered on to a database designed for the clinic. A full report detailing the diagnosis, results of investigation, and proposed management was automatically generated from the database and sent to the general practitioner, usually within 24–48 hours of assessment.

These investigators use a prospective, descriptive study to investigate whether the rapid access approach is useful for the evaluation of patients with symptoms suggestive of a new cardiac arrhythmia. The participants are patients referred by their general practitioner or the emergency department with symptoms suggestive of a new cardiac arrhythmia. The outcome measures are number of patients with a newly diagnosed significant arrhythmia, number of patients with diagnosed atrial fibrillation, and number of eligible, moderate, and high-risk patients treated with warfarin.

Findings

Over a 25-month period, 984 referrals were assessed. The referral rate was subsequently 1.0– 1.3/100,000 population each weekday. The mean number of patients seen each month was 42 (range 30–56). The number of patients seen each weekday varied from none to seven. The median time from referral to assessment was one day. The majority of referrals were from local general practitioners (81%), with an additional 15% of referrals from the emergency department. The mean age was 55 years (range 20–90 years) and 56% were women. The most common presenting symptom was palpitations (76%), followed by dyspnoea, dizziness, chest pain, and syncope.

As part of their initial assessment all patients had an ECG, 97% had blood tests, and 93% were fitted with a Holter monitor according to protocol. In addition, those with atrial fibrillation underwent echocardiography (95%) and chest radiography (93%). A further 14% and 12% of patients without atrial fibrillation underwent echocardiography and an exercise tolerance test, respectively, because of clinical indications, mostly to evaluate murmurs or chest pain. Two thirds of patients were discharged back to their general practitioners after the first visit to the rapid access arrhythmia clinic and a third were followed up as cardiology outpatients or referred to the arrhythmia clinic.

A significant cardiac arrhythmia was newly diagnosed in 40% of patients referred to the rapid access arrhythmia clinic. The most common arrhythmia was atrial fibrillation, with 203 new cases (21%). Among those with atrial fibrillation, the most common presenting symptom was dyspnoea, followed by palpitations, chest pain, and dizziness. Of these, 74% of eligible patients over 65 were treated with warfarin. Other arrhythmias diagnosed were supraventricular tachycardias (127 (13%)), conduction disorders (43 (4%)), and non-sustained ventricular tachycardia (21 (2%)). Vasovagal syncope was diagnosed for 53 patients (5%). The most frequent diagnosis was symptomatic ventricular and

45 supraventricular extrasystoles (355 (36%)). The investigators concluded that a rapid access arrhythmia clinic was an innovative approach to the diagnosis and management of new cardiac arrhythmias in the community. It provides a rapid diagnosis, stratifies risk, and leads to prompt initiation of effective treatment for this population.

The investigators found that palpitations and syncope are common symptoms, which may be caused by serious, yet treatable arrhythmias. They proposed that the rapid access model could be applicable to patients presenting in primary care with suspected cardiac arrhythmias and established a patient centred service modelled closely on their rapid access chest pain and heart failure clinics. Given the periodic nature of paroxysmal arrhythmias, prompt assessment when patients are most symptomatic will increase the chances of a definitive diagnosis compared with conventional outpatients. In the rapid access arrhythmia clinic, the median wait from referral to consultation was just one day. New arrhythmias were referred to a consultant electrophysiologist and patients with a new diagnosis of atrial fibrillation were fully evaluated in one consultation. This resulted in early risk stratification and initiation of warfarin, which may improve their prognosis, as the risk of stroke is reported to be highest in the early months after diagnosis of atrial fibrillation.

This rapid access model also has value for patients without serious disease. For patients who experience palpitations and are frequently concerned that they might have some serious cardiac pathology, a long wait for specialist investigations is avoided. The initial clinical assessment based on careful history taking, physical examination, and resting 12 lead ECG proved to be very accurate in assessing patients with symptomatic extrasystoles and anxiety related symptoms. Holter monitoring made little difference to their final diagnosis, suggesting that this is not routinely required when the initial assessment points to one of these diagnoses. It proved most useful in recording other supraventricular tachycardias (an additional 94 of 127 cases), non-sustained ventricular tachycardia (an additional 20 of 21 cases), conduction disease (an additional 20 of 43 cases), and to a lesser extent atrial fibrillation (an additional 33 of 203 cases), establishing a diagnosis for 123 patients with an initial assessment of ‘possible arrhythmia’. The investigators indicate that a clinical trial is needed to determine whether this intervention results in better or cheaper delivery of care than conventional models and that there may be other ways of assessing such patients, distinct from standard cardiology outpatient clinics. They also suggest that a simpler service model may be to provide open access ambulatory (Holter) monitoring to general practice but note that some general practitioners may feel that they do not have the frequency of exposure to interpret the results of the Holter and that this model would not result in the comprehensive clinical evaluation provided by the rapid access arrhythmia clinic. Another option they mention is to establish a rapid access atrial fibrillation clinic as this was the most common arrhythmia diagnosed and a key achievement of the clinic was the provision of a full clinical assessment with early initiation of anticoagulation. However, this would not cater for all patients with arrhythmia related symptoms. The approach adopted provides a rapid diagnosis, stratifies risk, and leads to prompt initiation of evidence-based treatments for patients presenting with suspected new cardiac arrhythmias.

3.2.2.4 Heart murmur clinics

A few brief descriptions of ‘murmur clinics’ are available in UK, US and Australian settings but there are no substantive studies. Around only one third of the people who suffer from this condition discover it and receive medical attention. However, the murmur can indicate the narrowing of the valve that connects the aorta artery with the heart, a condition that can result in sudden death. When the problem is detected early, it can be resolved by implanting an artificial valve. All the patients with aortic valve problems present a heart murmur. With the establishment of the ‘murmur clinics,’ the

46 idea is to identify those patients who have this heart murmur and determine if they have damage to the valve and are in danger. Heart murmurs in children younger than two years of age can be benign, but murmurs in older persons tend to be dangerous. According to the American Heart Association (AHA), when the valve opening narrows to about one-fourth its original size, symptoms are common. The most common symptom of an obstructed or leaky aortic valve is shortness of breath with exertion, which usually develops gradually over time, and some patients experience chest pain, lightheadedness or fainting.

One pathway for murmur has been identified. Under the Papworth Direct One Stop Service Murmur pathway78, the patient presents at the GP surgery with a murmur or known valve disease. The GP should undertake a full history, examination, bloods for Urea and Electrolytes (U and Es), full blood count (FBC) plus ECG. ECG is available as an open access test via Papworth Direct to aid GP diagnosis. The indicators for referral to Papworth Direct are evidence of murmur or known valve disease. All patients referred into the murmur pathway have a repeat ECG, then a transthoracic echocardiogram, and any other required tests. They will then have a consultation with the medical specialist who will decide the treatment plan.

3.2.3 The first long-term findings of rapid access clinics

The first long-term (2002-11) findings of rapid access cardiology clinics were published in 2012. This longitudinal data provides insight into their efficacy and role in providing a comprehensive referral service for primary care. Over this nine-year period, around 12,000 patients were seen at the Charing Cross rapid access clinics for chest pain, arrhythmia, and heart failure. Demand for these services has shown a steady rise over the period. The proportion of patients diagnosed with significant cardiac disease across all rapid access clinics has not changed significantly. The most commonly diagnosed arrhythmia was atrial fibrillation (15% of all attendances).

The importance of this study for the establishment of breathlessness clinics is that it provides a breakdown of all diagnoses in these rapid access clinics. Over the nine-year period, the proportion of patients attending rapid access chest pain clinics diagnosed with a cardiac cause for chest pain remained in a narrow range of 18-22% (mean 20%) per year. This was also the case with non-cardiac chest pain, showing a range of 74.4% to 80.6%. Patients receiving a diagnosis of ‘Other’ (patients receiving a diagnosis of non-cardiac disease in this cohort) received a range of diagnoses, including, but not limited to, pulmonary embolus, liver cirrhosis, thyrotoxicosis, malignancy, and substance misuse.

A similar finding of diagnostic consistency was reported for patients attending rapid access arrhythmia clinics over the nine years. Patients diagnosed with significant pathology (significant arrhythmia, other significant cardiac disease or other significant non-cardiac disease) remained in the range of 23-36% (mean 28%) per year. Of those patients diagnosed with significant arrhythmias atrial fibrillation/flutter was the most common, with an average of 70.8% over the nine years, followed by other Supraventricular Tachycardia (average 13.8%), Bradyarrhythmia (average 13.3%), and Ventricular tachycardia (average 2.1%). Only in rapid access heart failure clinics was there more variability: definite heart failure, range, 14.2%-40.3%, possible heart failure, 6.0%-28.0%, and not heart failure, 40.0%-69.7%.

78 http://www.papworthdirect.nhs.uk/pdfs/Papworth-Direct-One-Stop-Service-Murmur-Pathway.pdf

Thus, this long-term review shows that the diagnostic yield has remained reasonably constant, even if the diagnosis was unclear in a significant proportion of cases (‘possible arrhythmia’, ‘possible heart failure’). This suggests a standardised approach to diagnosis has been achieved in these rapid access clinic models.

The long-term review affirmed the findings of short-term studies that this model of care provides prompt diagnosis, risk stratification and management, and an approach that is viewed positively by GPs and patients. The investigators conclude that their model of responsive, secondary care-based service is a viable alternative to a community-based, GP-led system of care as the appropriate model for the initial assessment of patients with suspected cardiac disease.

3.3 Breathlessness

NICE defines breathlessness (dyspnoea) as the distressing sensation of a deficit between the body’s demand for breathing and the ability of the respiratory system to satisfy that demand. Breathlessness can be classified by its speed on onset as: acute breathlessness, when it develops over minutes, hours or days, and chronic breathlessness, when it develops over weeks or months.

The main causes of breathless are cardiac, pulmonary, and other causes such as psychogenic breathlessness. Common cardiac causes of breathlessness include silent myocardial infarction, cardiac arrhythmia, acute pulmonary oedema, and chronic heart failure. Common pulmonary causes of breathlessness include asthma, chronic obstructive pulmonary disease (COPD), pneumonia, and pulmonary embolism. Other common cases of breathless include anaemia, diaphragmatic splinting (due to obesity or pregnancy), and psychogenic breathlessness.

The management of breathlessness according to NICE includes determining the need for emergency admission by assessing the person's blood pressure, pulse, temperature, level of consciousness, peak expiratory flow rate (PEFR), oxygen saturation, and (if possible) electrocardiogram (ECG). Emergency admission is appropriate for people with: respiratory rate of more than 30 breaths per minute; tachycardia greater than 130 beats per minute; systolic blood pressure less than 90 mmHg, or diastolic blood pressure less than 60 mmHg (unless normal for them); oxygen saturation less than 92%, or central cyanosis (if the person has no history of chronic hypoxia); PEFR less than 33% of predicted; altered level of consciousness; a large respiratory effort (particularly if the person is becoming exhausted); stridor; clinical features of a pulmonary embolus or pneumothorax; and ECG suggesting a cardiac arrhythmia or myocardial infarction. Emergency admission should be considered, depending on the severity and number of risk factors present and if the person has breathlessness associated with specific factors, e.g. elevated respiratory rate (but if it is more than 30 breaths per minute, emergency admission should be arranged), tachycardia, hypotension, and others. If emergency admission is not indicated, the underlying cause of breathlessness should be managed and investigations arranged to identify or confirm the underlying cause of breathlessness.

With respect to investigations for acute breathlessness, if the person does not have an indication for emergency admission, NICE recommends that investigations should be arranged to identify or confirm the underlying cause of breathlessness. For acute breathlessness of uncertain cause, the following should be undertaken: Chest radiography, to look for signs of heart failure and pulmonary pathology (including pleural effusion); electrocardiogram (ECG), to look for signs of heart failure, arrhythmia, and pulmonary embolism; spirometry or peak expiratory flow rate, to look for signs of obstructive airway disease; full blood count, to check for anaemia; C-reactive protein or erythrocyte sedimentation rate (ESR), for evidence of infection; and other investigations guided by clinical findings.

Where suspected acute asthma or an acute exacerbation of chronic obstructive airways disease (COPD), airways obstruction should be assessed by spirometry (airway obstruction is confirmed by a forced expiratory volume in 1 second (FEV1) less than 80% of the predicted value and FEV1/forced vital capacity (FVC) ratio less than 70%). Asthma should be distinguished from COPD, based on: smoking history, almost always present in people with COPD; age, usually older than 35 years of age for COPD; chronic productive cough, common with COPD, uncommon with asthma; breathlessness, progressive with COPD, variable with asthma; and variability of symptoms, common with asthma, uncommon with COPD.

If asthma and COPD cannot be distinguished based on clinical features, measurements should be arranged of peak expiratory flow rate (PEFR), morning and nighttime and during symptoms (to assess variability). If doubt continues, a large response (greater than 400 mL) to bronchodilators or prednisolone (30 mg orally per day, for 14 days) is characteristic of asthma but not COPD. If there is still doubt, the person should be referred for a specialist's opinion. For people with COPD, chest radiography should be arranged to exclude other serious lung pathology (such as lung cancer). For suspected acute exacerbation of bronchiectasis, chest radiography should be arranged to exclude other causes for the symptoms. The person should be referred to a respiratory specialist for confirmation of the diagnosis (by high-resolution computed tomography scanning). For suspected pneumonia, chest radiography should be arranged if the person is older than 50 years of age and smokes (to exclude underlying cancer). For other people who are well enough to be managed in the community, chest radiography is not required to confirm the diagnosis. For suspected lung/lobar collapse or suspected pleural effusion, chest radiography should be arranged to confirm the diagnosis.

3.3.1 Symptom-based vs disease-based approach to assessment and diagnosis

Clinical guidelines and care pathways for a number of aspects of breathlessness tend to be disease- specific, lack cost-effectiveness data, and do not take satisfactory account of multi-morbidity.

IMPRESS sets out a number of advantages for taking a symptom-based approach rather than a disease-based approach to assessment and care of adults who have long-term breathlessness79 and some of these are further supported by the wider evidence base:

Firstly, this approach can harmonise potentially different approaches advised by different specialties to assessment and treatment of breathlessness and therefore reduce variation. The current unwarranted variation in diagnostic rates leads to overuse, misuse, underuse, and under-coordination of care. This will involve reviewing diagnostic approaches across services and to harmonise approaches between diseases. For example, quality assured spirometry is needed to ensure accurate diagnosis of COPD. IMPRESS’s observation is confirmed by a recent systematic review regarding the facilitation of knowledge exchange80. Of the 14 studies that examined the impact on health-care quality of some form of vertical boundary-spanning intervention, the only one to examine patient outcomes as a result of a boundary-spanning initiative (Thompson et al. 199681) used key indicators (through retrospective chart audit) to determine the quality of peritoneal dialysis before and after a collaborative mapping project. Inpatient and ambulatory nursing representatives met to identify and change process flow- charting for equipment utilisation (by patients and clinicians) across a service boundary. As an intentional quality improvement effort, patients who received care after the new jointly developed guidelines were implemented showed a decrease in transfer time between units, faster diagnosis and faster treatment of complications; plans for interdisciplinary collaboration for changing practice responses for hypovolaemia were also being monitored. Although this study did not qualitatively

79 IMPRESS. Breathlessness IMPRESS Tips (BITs) for commissioners. Primary Care Respiratory Society UK and Optimal Respiratory Health. 80 Nasir L, Robert G, Fischer M, Norman I, Murrells T, Schofield P. Facilitating knowledge exchange between health-care sectors, organisations and professions: a longitudinal mixed-methods study of boundary-spanning processes and their impact on health-care quality. Health Serv Deliv Res 2013;1(7). 81 Thompson MA, Diccion S, Hensick J, Armstrong S. Spanning organizational boundaries to improve care and service: inpatient and outpatient chronic peritoneal dialysis. J Nurs Care Qual 1996; 11:9–15. http://dx.doi.org/10.1097/00001786-199612000-00004.

50 examine how different professionals were brought together for discussions, it nicely illustrates the impact of the effort.

Secondly, it guides the system to start at the point where people present to primary care – with symptoms not diagnoses – and suggests how to support the system to increase diagnosis rates in at least three under-diagnosed conditions: COPD, heart failure and anxiety, which, if left untreated cause significant morbidity and high use of acute services. These three conditions are the main diagnoses associated with breathlessness and all are underdiagnosed in primary care82.

For example, a total of nine primary studies carried out either wholly or partially with the UK population have reported late diagnosis of COPD. Bastin et al (2010)83 sought to characterise patients (n=41) at first admission with an acute exacerbation of COPD. Despite having severe disease, a diagnosis of COPD had not been made in the community prior to admission in one-third of patients. Bolton et al. (2004)84 aimed to assess the impact of spirometry in general practice (72% of general practices with spirometry in Wales). Despite incentives to perform spirometry in general practice, lack of adequate training in use and interpretation suggests use is confounded and the diagnosis of COPD is likely to be made on imprecise clinical grounds. Calderón-Larrañaga et al (2010)85 aimed to determine associations between population characteristics, diagnosed and undiagnosed COPD prevalence, primary healthcare factors, and COPD admission rates by primary care trust (PCT) and general practice levels in England (53,676,051 patients in 8,064 practices in 152 English PCTs). Admissions were strongly associated with population deprivation. In a practice-level multivariate Poisson regression, registered and undiagnosed COPD prevalence, smoking prevalence and deprivation were risk factors for admission (p < 0.001), while healthcare factors - influenza immunisation, patient-reported access to consultations within two days, and primary care staffing - were protective (p < 0.05). Frank et al (2006)86 collected information on the underdiagnosis of COPD in the UK: in two practices (825 patients) the study found a considerable under-recording of COPD. Hassett et al (2006)87 aimed to establish a Community Respiratory Assessment Unit and to evaluate its role in enhancing the accuracy of respiratory diagnosis in primary care. Amongst 364 patients, the single biggest diagnostic group consisted of patients with definite or suspected COPD, but the

82 Department of Health, England. An outcomes strategy for people with chronic obstructive pulmonary disease (COPD) and asthma in England. 2011; Tylee A, Walters P. Underrecognition of anxiety and mood disorders in primary care: why does the problem exist and what can be done? J Clin Psychiatry 2007; 68 Suppl 2: 27-30; DH Cardiovascular Disease Team. Cardiovascular Disease Outcome Strategy. March 2013. 83 Bastin A J J; Starling L, Ahmed R, Dinham A, Hill N, Stern M, Restrick L J J; (2010) High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation.. Chronic Respiratory Disease. 7(2): 91-7. 84 Bolton C E E; Ionescu A A A; Edwards P H H; Faulkner T A A; Edwards S M M; Shale D J J; (2004) Attaining a correct diagnosis of COPD in general practice. Respiratory medicine. 99(4): 493-500. 85 Calderón-Larrañaga Amaia, Carney Leanne, Soljak Michael, Bottle Alex, Partridge Martyn, Bell Derek, Abi- Aad Gerrard, Aylin Paul, Majeed Azeem (2010) Association of population and primary healthcare factors with hospital admission rates for chronic obstructive pulmonary disease in England: national cross-sectional study. Thorax. 66(3): 191-6. 86 Frank Timothy L L; Hazell Michelle L L; Linehan Mary F F; Frank Peter I I; (2006) The diagnostic accuracies of chronic obstructive pulmonary disease (COPD) in general practice: The results of the MAGIC (Manchester Airways Group Identifying COPD) study.. Primary care respiratory journal : journal of the General Practice Airways Group. 15(5): 286-93. 87 Hassett Rosemarie, Meade Karen, Partridge Martyn R R; (2006) Enhancing the accuracy of respiratory diagnoses in primary care: a report on the establishment of a Community Respiratory Assessment Unit. Primary care respiratory journal : journal of the General Practice Airways Group. 15(6): 354-61.

51 diagnosis was often not confirmed. Jordan et al (2010)88 describe the extent of undiagnosed clinically significant COPD in England and the effectiveness of an active compared with an opportunistic approach to case finding is evaluated. Amongst 20,496 participants 971 (4.7%) had clinically significant COPD, of whom 840 (86.5%) did not report a previous diagnosis. Undiagnosed cases were more likely to be female and to have smoked less. 25.3% had severe disease (Forced Expiratory Volume (FEV1) <50% predicted), 38.5% Medical Research Council (MRC) grade 3 dyspnoea, and 44.1% were current smokers. The active case-finding strategy can potentially identify 70% more new cases than opportunistic identification alone (3.8 vs 2.2 per 100 targeted). Treating these new cases could reduce hospitalisations by at least 3300 per year in England and deaths by 2885 over 3 years. Nacul et al (2011)89 estimated local underdiagnosis of COPD as the ratio of observed to expected cases and investigated geographical patterns using classical and geographically weighted regression analysis. Both observed and expected prevalence of COPD varied widely between areas. There was evidence of a north-south divide, with both observed and modelled prevalence higher in the north. The ratio of diagnosed to expected prevalence varied from 0.20 to 0.95, with a mean of 0.52. Underdiagnosis was more pronounced in urban areas and was particularly severe in London. Tinkelman et al. (2007)90 performed spirometry in smokers aged 40 years and over drawn from general practices in two countries to document the extent of underdiagnosis in a high-risk group of ambulatory patients. 818 patients were recruited from primary care practices in Aberdeen, Scotland, and Denver, Colorado. The investigators concluded that screening of smokers over 40 in general practice might yield 10 - 20% undiagnosed COPD cases, with a substantial proportion of these having moderate to severe disease. Finally, Walker et al (2006)91 examined whether improving rates of diagnosis amongst 1508 subjects led to improvements in pharmacological and nonpharmacological management. Of the 235 subjects, 130 received a new diagnosis, most commonly COPD. The patients with COPD were significantly undertreated before spirometry. Testing led to a significant increase in the use of anticholinergics (37 versus 18%), long-acting beta-agonists (25 versus 8%) and inhaled steroids (71 versus 52%).

Thirdly, it has the potential to address multi-morbidity (the co-concurrence of two or more long-term conditions in a person). The Department of Health has prioritised actions on comorbidities, producing a framework of interconnected principles for action in the wider health and care system92. It argues that the single disease approach is unable to address the problem of comorbidity appropriately, as multiple morbidities are becoming the norm (the number of people with comorbidities in England being projected to increase from 1.9 million to 2.9 million during 2008-2018). Moreover, with the personalisation of care, specific populations need to be identified for targeted interventions. These comorbidities may be of several types: ‘diagnostic overshadowing’ where one condition is clinically dominant; synergistic, related to how they arise and are treated; and coincidental (where disease

88 Jordan Rachel E E; Lam Kin-bong Hubert B; Cheng Kar Keung K; Miller Martin R R; Marsh Jennifer L L; Ayres Jon G G; Fitzmaurice David, Adab Peymané (2010) Case finding for chronic obstructive pulmonary disease: a model for optimising a targeted approach. Thorax. 65(6): 492-8.

89 Nacul Luis, Soljak Michael, Samarasundera Edgar, Hopkinson Nicholas S; Lacerda Eliana, Indulkar Tejal, Flowers Julian, Walford Hannah, Majeed Azeem (2011) COPD in England: a comparison of expected, model- based prevalence and observed prevalence from general practice data†.. Journal of Public Health 33(1): 108-16. 90 Tinkelman David G G; Price David, Nordyke Robert J J; Halbert Ronald J J; (2007) COPD screening efforts in primary care: what is the yield?. Primary care respiratory journal : journal of the General Practice Airways Group. 16(1): 41-8. 91 Walker P P P; Mitchell P, Diamantea F, Warburton C J J; Davies L (2006) Effect of primary-care spirometry on the diagnosis and management of COPD. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 28(5): 945-52. 92 Aitsi-Selmi A. Comorbidities. A framework for system-wide action. London: Department of Health, 2014.

52 management is separate). An example of a synergistic comorbidity is COPD and heart disease. For example, only 14-18% of people with COPD only have COPD and when actively assessed for comorbidities it may be as low as 3%. In one study of 284 patients attending a dyspnoea clinic, 40 patients (14%) suffered from a combination of heart and lung disease93. If not all of the morbidities are diagnosed and managed, this will also worsen health outcomes and may lead to higher use of unscheduled care.

Thus, the framework of principles emphasises, for example, early diagnosis and treatment, community-based approaches, equitable resource allocation and service access, the development of joint guidelines and algorithms, the identification of high-risk patients with comorbidities who are frequent service users and run dedicated clinics for them, and addressing comorbidities holistically based on symptoms rather than individual diseases (in this context the framework mentions PHE’s breathlessness campaign piloted in Oldham and Rochdale94).

Fourthly, this approach can also address the complex interaction between mental and physical health and address parity of esteem. The framework recommends considering ‘mental illness as a long-term condition on a par with physical illness’ and ‘treated as closely linked’. Costs for these comorbidities involving both physical and mental illness being usually higher and can increase mortality significantly.

Fifthly, it requires the healthcare system to be alert to patients’ capabilities, opportunities and motivation for healthy or unhealthy behaviours that contribute to their symptom, and to one or more underlying condition and to ‘make every contact count’. Early diagnosis of breathlessness, for example, can result in early referral to stop smoking services where the underlying condition indicates this.

3.3.2 Investment and disinvestment decisions for breathlessness services: prerequisites

IMPRESS emphasises the importance of a number of factors in making decisions about investment/disinvestment in services. A shared knowledge of the evidence base, including the local populations’ needs and health status is needed. This may be achieved by a joint strategic needs assessment (JSNA) and mapping of local services; an assessment of what already exists and is provided for by the various sectors (health authorities, local authorities, and the voluntary sector). Assessment and care services for breathlessness may be located in primary care, specialist primary care, community respiratory teams, community heart failure teams, combined primary and secondary care services, outpatients, and inpatients. IMPRESS advises to ‘aim to develop symptom-based pathways over time working with the evidence and relevant local experts from practice Teams, respiratory, cardiology, mental health services and obesity. It suggests running a local ‘decision conference’, as developed by the London School of Economics and Health Foundation, where professional colleagues bring and review the cost-effectiveness evidence and prioritise interventions, before taking appropriate decisions on commissioning95.

93 Nielsen LS, Svanegaard J, Wiggers P, Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. Journal of Internal Medicine 2001; 250: 422-428. 94 http://www.hmr.nhs.uk/index.php/news/325-rochdale-pilots-first-ever-breathlessness-campaign 95 Health Foundation and London School of Economics and Political Science: Star – socio-technical allocation of resources. See: http://www.health.org.uk/learning/star

IMPRESS also encourage the fostering of integration across specialties: ‘The service will need to integrate mental and physical health pathways and services to achieve parity of esteem, and a common and consistent approach to behaviour change across a number of health specialties and public health’. As noted, systematic review evidence shows that boundary-spanning processes across specialties can be beneficial with respect to faster diagnosis and earlier treatment of complications.

IMPRESS have argued that local provision should be checked to see how it matches the IMPRESS algorithm (see later) which provides clinicians with an evidence-based integrated approach to assessment and treatment for breathlessness.

Such a review may lead to a number of changes, such as the redesign of breathlessness diagnostic and assessment pathways, or the commissioning of new services such as dedicated earlier diagnosis breathlessness clinics, the provision of such assessment services by all practices vs. selected practices with a special interest in breathlessness. IMPRESS suggests two organisational models: a federated model, with each general practice providing a core service, and then referring to a triage or primary care practitioner with a special interest; a breathlessness assessment service commissioned from a local hospital, which has diagnostic equipment such as echocardiography and chest X-ray on site.

3.3.3 What is needed to assess breathlessness?

IMPRESS have indicated, in its Breathlessness IMPRESS Tips (BITs) for clinicians, that the following essential equipment is needed for the assessment of breathlessness:

. Oximeter . Watch/clock/computer/smartphone . Stethoscope . Blood pressure measure . Calibrated weighing scales . Height measure . Thermometer . Peak Expiratory Flow Meter/microspirometer . Expired carbon monoxide monitor

Additional equipment required or local access to:

. Chest X-ray . Spirometer . Tape measure . ECG machine . BNP testing with hospital analysis . Echocardiography

NICE does not recommend echocardiography in primary care. However, given that echocardiography may be crucial to the diagnosis of heart failure, there may be limitations to locating early diagnosis breathlessness clinics in general practice if local access to echocardiography cannot be obtained. A retrospective case-control series from the Mayo Clinic in the USA indicated that echocardiography

54 and resulting changes of medical treatment might improve survival in patients fulfilling clinical criteria of heart failure96.

3.3.4 Examples of current models

As with rapid access chest pain clinics, it is unlikely that one service model will emerge to fit all circumstances. Timmins et al (2006), for example, conclude that: ‘…there is no single model of care that best serves the main purpose of RACPCs to see patients with undifferentiated chest pain within 14 days of referral and to diagnose and initiate appropriate treatment in those with angina’. Rather, it is likely that diagnostic breathlessness clinics will evolve to reflect local resources, local needs, and the priorities set by consultants, hospitals, and clinical commissioning groups.

A number of examples of service configurations to support earlier diagnosis of diseases related to breathlessness as a symptom have been identified. Some of the diagnostic breathlessness clinics identified in the literature are poorly described. These include, for example, Bolton Health’s Respiratory Disease JSNA refers to the Rapid Access Breathlessness Clinic, commissioned to provide assessment, diagnostic tests and treatment to new onset of symptom, breathless patients but no further details are provided97. Kettering General Hospital NHS Trust operates a one-stop breathlessness clinic on referral by a GP but, again, no details are available98. Similarly, documents refer to a rapid access breathlessness clinic to assess cardio-respiratory disease, in the Upper Eden Valley and funded through the Closer to Home Programme. The clinic located in a community hospital runs fortnightly and can also be used by GPs for diagnostic uncertainty99. Dartford, Gravesham and Swanley Primary Care Trust reports the development of a breathlessness clinic to provide community diagnostic services for patients, many of whom may have heart failure100.

1. The Current Service Model for Diagnosing Breathlessness

While there has been no systematic attempt to document current practices across England for diagnosing breathlessness in primary and secondary care, the model used in Ashton, Leigh and Wigan prior to the introduction of a new service model is probably typical101.

Primary and secondary care have an important role in diagnosing breathlessness patients though the involvement of each may depend on the complexity of the patient and the capacity and confidence of the practice. Nearly all breathless patients present in primary care; a small proportion of patients without a confirmed notice present in secondary care following acute exacerbation. For patients presenting in primary care, the general practitioner may initiate a range of investigations:

96 Senni M, Rodeheffer RJ, Tribouilloy CM, et al. Use of echocardiography in the management of congestive heart failure in the community. J Am Coll Cardiol 1999; 33: 164-70. 97 Bolton’s Health Matters. JSNA. Respiratory Disease. n.d. Accessed at: http://www.boltonshealthmatters.org/sites/default/files/Respiratory%20Disease%20JSNA%20Chapter.pdf 98 Kettering General Hospital NHS Trust. Minutes of Patient and Public Council Meeting. 1st March 2007. 99 Ross A. Playing field far from level. Pulse, 20 April 2006, p. 19; NHS Cumbria. Eden Locality Board Minutes, 20 October 2009; NHS Cumbria. Strategic Plan 2008-13. 100 http://www.publications.parliament.uk/pa/cm200506/cmhansrd/vo060904/text/60904w0108.htm 101 See: Ashton, Leigh and Wigan NHS. Practice Based Commissioning. Patient Focus/Atherleigh Consortium. Proposal for Commissioning Plan for Breathlessness. Accessed at: http://www.alpfhealth.org.uk/docs/breathlessness.pdf

. Peak expiratory flow rate (PEFR) reversibility/variability in order to diagnose asthma . Spirometry with reversibility in order to diagnose COPD/Asthma/Restrictive lung disease . ECG for patients with suspected Heart Failure/Arrhythmias . B-type Natriuretic Peptide (BNP) Blood Test for patients with suspected Heart Failure which if reported abnormal results is an automatic referral for echocardiography. If echocardiography reports are abnormal, patients receive an automatic outpatient department appointment with a cardiologist.

Once a diagnosis is made treatment is frequently initiated in primary care by the general practitioner or practice nurse. A proportion of patients are referred directly to specialist services in secondary care or tier 2 of the respiratory team for diagnosis.

Outcomes: Two drawbacks to this service model have been identified: the length of time and the amount of resources required to achieve an accurate diagnosis for complex patients; and the high numbers of patients currently misdiagnosed and receiving incorrect treatment. COPD as noted is frequently misdiagnosed and studies have shown that the clinical suspicion of heart failure can only be confirmed by echocardiography in around half of patients102.

2. Outpatient breathlessness clinic run jointly by cardiology and respiratory consultants

The University Hospital of North Staffordshire NHS Trust103 has set up an outpatient breathlessness clinic run jointly by a cardiologist with a special interest in heart failure and a respiratory consultant. It was designed by the consultants and then tested with CCGs and continues to be adapted. It provides new assessments and follow-up appointments for unexplained breathlessness; patients with a previous diagnosis of COPD and heart failure are excluded because there are other community respiratory and cardiology services available. Referrals are made by GPs on a specific referral form, accompanied by diagnostic test results gained within the last month for BNP, ECG, spirometry and chest X-ray.

Outcomes: No outcomes are available for this service.

3. Improved diagnosis of breathless patients through GP referral to a one stop shop diagnostic service

The service model currently in operation was set up by Ashton, Leigh and Wigan PCT in 2010 as part of the Patient focus/Atherleigh consortium proposal for the commissioning plan for Wigan Breathlessness Service. The service was initially set up as a pilot across a third of the borough and has since been expanded to cover half. This service is part of the ongoing service development of respiratory care in Wigan104.

102 Remes J, Miettinen H, Reunanem A, Pyorala K. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J 1991; 12: 315-21; Francis CM, Caruana L, Kearney P, et al. Open access echocardiography in management of heart failure in the community. BMJ 1995; 310: 634-6. 103 Cited by IMPRESS. Breathlessness IMPRESS Tips (BITs) for commissioners, p. 9. 104 I am grateful to Wendy Fairhust and Jay Mangan for information on the Ashton, Leigh and Wigan service. Background information is available in: (i) Commissioning Success (www.commissioningsuccess.com). Stop and Breath. Accessed at: http://content.yudu.com/A29wn2/cssample/resources/20.htm (ii) The service model is fully described in: Ashton, Leigh and Wigan NHS. Practice Based Commissioning. Patient Focus/Atherleigh Consortium. Proposal for Commissioning Plan for Breathlessness. V 6.6 (73pp). The service is also described in other documents, including (iii) IMPRESS. Breathlessness IMPRESS Tips (BITs) for commissioners, p. 9 (Health First ALW Community Interest Company in Atherleigh). The service also offers enhanced management reviews of medication, inhaler technique, treatment optimisation, personalised care plans, stop smoking support, vaccination, education, and referrals to PR, warm home schemes and other services

The service model encompasses diagnosis and enhanced care, the objective of the former being to improve the diagnosis of people presenting with conditions resulting in breathlessness (COPD, Asthma, and Heart Failure). A secondary aim is the improvement of data collection in primary, community and secondary care. The pathway for the improved diagnosis of patients incorporates the introduction of a One Stop Shop to aid diagnosis of causes of breathlessness. Compliance is achieved amongst GPs by training, support and audit.

The service is delivered in collaboration with Health First ALW Community Interest Company – a GP federation , Bridgewater Community Foundation Trust and Wrightington, Wigan and Leigh Acute Trust.

Breathless patients who present in primary care where there is diagnostic uncertainty (defined as aged >50 with a past medical history of cardiovascular disease, peripheral arterial disease, hypertension or diabetes in primary care) are referred to the One Stop Shop on receipt of the blood results including BNP. It is recommended that the patient has had a chest X-Ray in the past 6 months if clinically indicated (the service will arrange this if this has not been performed). The service adopts a structured approach to diagnosis, firstly excluding heart failure where this is a possibility, then going on to diagnose respiratory conditions by spirometry if heart failure is ruled out.

If heart failure is a possibility (i.e. if BNP is raised) an echocardiogram is performed which is interpreted by a cardiologist who prepares a management plan which may exclude the need for an outpatients appointment. If the BNP test or the echocardiogram and ECG are negative, the patient has a respiratory assessment including spirometry with reversibility. This is interpreted by a specialist advanced nurse practitioner who then formulates a management plan with the patient. If the diagnosis is still unsure or complex, the patient is seen by a respiratory consultant, working in Primary Care with the breathlessness service. The sequence of tests following history in the one stop shop is: BNP, Echocardiogram, and ECG, spirometry with reversibility).

The service was set up in response to audits, which showed that patients with COPD are often not diagnosed and managed effectively leading to exacerbations and admissions. Random investigation leads to inappropriate investigation and inefficient use of resources. Everyone with an abnormal echocardiogram goes to the cardiology department; many patients are referred inappropriately to respiratory specialists in the acute sector. Inhalers are overprescribed through inappropriate diagnosis of asthma and COPD. Under the ‘new model’, improved diagnosis reduces morbidity and mortality and reduces admissions. It also results in appropriate investigations and reduces exacerbations through patients being given appropriate treatments. Only those who need to have a cardiology or respiratory outpatient’s appointment are referred. Heart failure patients are not given inhalers inappropriately, thereby reducing expenditure on these.

Outcomes: It is to be emphasised that this is not a stand-alone service but works in conjunction and in collaboration with the acute and community services already existing. The enhanced care arm of the service is also crucial in terms of the outcomes. This part of the service utilises specialist nurses who review patients holistically and proactively case find in Primary Care. Patients are seen in their own practices ensuring prompt data entry, improved communication and prompt changes to medication. The emphasis of the review is not disease specific; nurses question and confirm existing diagnoses,

such as weight management. See also: http://www.alpfhealth.org.uk/pubdocs/ALPF_NEWSLETTER_DEC_20101.pdf

57 optimise treatment plans and promote self-care. A holistic long-term conditions template has been developed for use on practice systems.

An evaluation of the service took place in 2011.This was a small-scale low cost pilot. It was evaluated after 12 months, which included a 4 month run in period, all findings were tentative. Specific financial outcomes related to the diagnostic part of the service were not examined. Overall and in the short term (the diagnosis service and the enhanced care service) was cost neutral (i.e. savings made covered the cost of the service). As the service was delivered for the pilot in 1/3rd of the borough results were compared with the other 2/3rds of the borough. There was a comparative reduction in outpatient’s appointments, unplanned admissions and medicines management costs. No other services were de-commissioned. However, this was evaluated over a very short period of time.

A much longer time frame is needed to evaluate the impact of quality improvements such as increased prevalence and more accurate diagnosis. The service is currently piloting the use of near patient testing for BNP negating the need for bloods to be taken prior to attendance at the service.

4. Hospital clinic-based dyspnoea examination programme for general practice105

Patients with dyspnoea of at least 2 weeks duration were offered a dyspnoea examination programme based in a clinic in Haderslev Hospital, Denmark. Seventy-four general practitioners in the region accepted to refer patients to the examination programme. All patients were examined within 2 weeks of referral. This broader examination programme was coordinated, permitting all examinations in an individual patient to take place within a few hours on the same day. The programme included physical examination, ECG, chest X-ray, lung spirometry, echocardiography and laboratory tests for anaemia, thyroid status, renal failure, and diabetes. Referral diagnosis, medical treatment, and degree and duration of dyspnoea were recorded in each patient. A Fletcher dyspnoea questionnaire was used for grading the dyspnoea at the first visit to the clinic and again after 6 months. Echocardiography was used to establish a diagnosis of systolic left ventricular dysfunction. A diagnosis of lung disease was established on the combination of clinical evaluation and spirometry. Other conditions were diagnosed according to conventional criteria.

Outcomes: The investigators concluded that ‘in most patients it seems to be too difficult to establish the background of dyspnoea in general practice’. Of 284 consecutive patients referred from general practice with dyspnoea, in only 39% of the patients was there concordance of the diagnosis on referral and the diagnosis based on the examination programme. While heart failure and lung disease was suspected in 126 and 79 patients, respectively, these diagnoses were confirmed in only one-third to half of the patients. Further, heart failure was revealed in 13 of 107 patients not suspected of heart failure (12%) and lung disease in 45 of 154 patients not suspected of pulmonary disease (29%). A change of treatment was suggested in 64% of all patients. After six months, improvement of dyspnoea was seen in more than half of the patients. Improvement in dyspnoea was recorded in 61% of patients in whom the changes of medical treatment were completed vs. 34% of patients in whom the recommended treatment advice was not taken. 97% of GPs referring patients indicated that they would appreciate permanent access to the dyspnoea examination programme.

105 Nielsen LS, Svanegaard J, Wiggers P, and Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. Journal of Internal Medicine 2001; 250: 422-428.

5. Pulmonary subspecialty clinic106.

This was an early study in a pulmonary subspecialty clinic to test whether, in patients with chronic dyspnoea, a diagnostic approach based on objective confirmation of suspected diagnoses would be better than one based on clinical impression alone. 85 patients were prospectively studied with a primary complaint of dyspnoea. The investigators achieved 100% success in determining the cause of dyspnoea compared with only 66% accuracy based on clinical impression alone. Four groups of disorders – asthma, chronic obstructive pulmonary disease, interstitial lung diseases, and cardiomyopathy – accounted for two thirds of the cases. Findings on the history and physical examination were inadequate to determine the specific diagnosis. Pulmonary function testing, including a methacholine bronchoprovocation challenge, were the most useful diagnostic tests, especially for COPD and asthma. Chest roentgenogram was most useful for interstitial lung disease and comprehensive exercise testing for dyspnoea due to psychogenic factors.

6. New one-stop breathlessness clinic, Chelsea and Westminster Hospital107

In May 2011, the Cardiac and Respiratory departments commenced a new, innovative one-stop clinic run by the service lead for Cardiology and the service lead for Respiratory Medicine. The service caters for breathless patients who may have underlying cardiac and/or respiratory pathology where there is diagnostic uncertainty or where dual input is required. Referred patients have the following at the same visit: ECG; Echocardiogram; Chest X Ray; Pulmonary Functions tests; Clinical assessment by Cardiac and Respiratory Consultants. Access to the clinic is available via Choose and Book.

Outcome: No formal evaluation has been undertaken. However, the clinic is stated to avoid multiple visits to hospital and enables patients to receive their diagnosis and where required, treatment in a timely, efficient manner.

7. Unexplained breathlessness one stop assessment service, Royal Brompton and Harefield NHS Foundation Trust108

This is a comprehensive, one-stop assessment to find out the cause of the patient’s breathlessness. It is run by a multi-disciplinary team with specialist experience and the approach uses advanced tests.

The patient undergoes a clinical review in the day unit of the hospital. The service then asks the patient to carry out some specialist breathing (lung function) test. It is likely that they may also need a blood test and chest X-ray (unless the patient has the results of recent tests). If the patient is able, the service will ask the patient to carry out a cardiopulmonary exercise test (CPET) (on either a walking treadmill or an exercise bike). A senior physiotherapist checks the patient’s breathing, discusses their breathlessness problems, and provides expert advice on how to help improve these problems. When all the tests have been completed, the service then goes through and discusses these results with the patient and their individual plan.

106 Pratter MR, Curley FJ, Dubois J, Irwin RS. Cause and evaluation of chronic dyspnoea in a pulmonary disease clinic. Arch Intern Med 1989; 149: 2277±82. 107 Chelsea and Westminster Hospital NHS Foundation Trust. GP Bulletin April 2011 Issue, New one-stop breathlessness clinic. 108 Royal Brompton and Harefield NHS Foundation Trust. Unexplained breathlessness one-stop assessment service. http://www.rbht.nhs.uk/patients/condition/unexplained-breathlessness-service/

The unexplained breathlessness service is linked with the asthma and allergy service, pulmonary hypertension unit, and cardiac teams at Royal Brompton Hospital, thereby drawing on leading expertise in a number of areas.

Outcomes: No outcomes are available.

8. Service level agreement for selected practices to provide spirometry, ECGs and 24 hour blood pressure monitoring: northern network of Barnet Clinical Commissioning Group109

Barnet Clinical Commissioning Group has taken a somewhat different approach to the clinic model. The northern network of Barnet Clinical Commissioning Group (CCG) is drawing up a service level agreement for selected practices to provide spirometry, ECGs and 24 hour blood pressure monitoring. The network of 32 practices has decided to support several practices to carry out the tests from late spring 2014. The CCG has worked with practices to develop primary care networks based on location, with the aim of releasing capacity in general practice. The networks will be expected to provide care that ensures the best use is made of the time, skills and training of each practice team member. The new diagnostics regime will be funded as part of the CCG’s network development programme. The service model is also designed to be cost saving; for example, an ECG performed by a trained member of practice staff will be cheaper than referring the patient to hospital. However, it is also designed to benefit patients, reducing waiting times as well as avoiding hospital visits. Amongst the patient clinical benefits identified include: hypertension medication will only be prescribed for patients with a confirmed diagnosis; patients with high blood pressure will be diagnosed at an earlier stage, reducing the risk of secondary diseases; and respiratory patients will be diagnosed at an earlier stage, ensuring they are taking the correct medication. Development work has been demanding, with service level agreements and key performance indicators outstanding.

The network anticipates selecting a number of practices to offer the services initially with a view to keeping the testing as local as possible but, ideally, with a spread of provision over the five local networks to ensure a geographical balance. Some local practices are already offering one or two of the three services but will have to meet the new service level agreement requirements if they are to be awarded the contract for the reshaped diagnostics. The service level agreement will include requirements around training the staff to provide the tests and equipment provision. Service delivery will be closely assessed, the monitoring process to encompass key performance indicators, patient experience surveys, and regular audit ranging from waiting times and offers of smoking cessation support through to the numbers of patients with newly-diagnosed hypertension and respiratory problems.

Outcomes: No outcomes are available.

3.3.5 Pathways

There is no consensus on the optimal pathway for the diagnosis of breathlessness. IMPRESS in collaboration with the London School of Economics (LSE) have compiled a non-linear algorithm that focuses substantially on precision with respect to each stage of the assessment. There are very few additional pathways for breathlessness clinics and none with as robust an evidence base.

109 Primary Care Commissioning. Barnet Network plans to make diagnostics the business of GPs. 3 March 2014. Accessed at: http://www.pcc-cic.org.uk/article/barnet-network-plans-make-diagnostics-business-gps

The IMPRESS Algorithm110

The IMPRESS Algorithm starts with the question: Should the patient be admitted? This requires assessment of blood pressure, oxygen saturation and pulse (using a digital pulse oximeter), measurement of peak expiratory flow (using peak flow meter). The patient is admitted if several criteria are met (such as a respiratory rate above 30 breaths a minute, central chest pain, and suspected unstable arrhythmia).

The algorithm then asks: ‘Does the patient already have a firm diagnosis? If yes (for example, COPD, asthma, etc.), then depending on readings NICE guidelines should be followed. If not, then a chronic breathlessness assessment should be undertaken. This should encompass: taking a good history (including current and past smoking history) to start ruling out/in common physical causes such as COPD, asthma, heart failure, anaemia, obesity, and anxiety; looking and listening to the patient to assess their general condition and appearance and measuring vital signs if not already performed; and coding the symptom to enable breathlessness register development.

The assessment should then consider the most likely diagnosis, what the patient believes is the cause of their breathlessness, whether the patient is still smoking, what medicines the patient takes for their condition and is the prescription being dispensed, explanation of what the medicines are prescribed for, and whether there could be an additional diagnosis. This step is then followed by giving the diagnosis, giving the five Leventhal components, based on the patient’s understanding, ideas, and expectations. The provision of information should be appropriate to the person’s reading age and learning style.

Testing for confirmation of the diagnosis might encompass routine blood tests, microspirometry, peak expiratory flow (PEF), carbon monoxide monitor, serial peak expiratory flow (PEF), ECG, natriuretic peptides, chest X-ray (CXR), measurement of neck circumference and waist circumference (if manageable). Depending on the patient’s history, physical and mental health assessment and chronicity, one of a number of options are then available: start treatment or refer to a treatment service, e.g. breathing training provided by respiratory physiotherapists; treat as part of the diagnosis (e.g. starting a course of medicines such as oral corticosteroids if an exacerbation of COPD); and carrying out further tests before starting treatment. The patient should be offered a personalised management plan summarising the agreed interventions. Behavioural interventions relating to smoking, alcohol, obesity, and general fitness should be considered. Talking therapy should address other contributing factors to the patient’s breathlessness, including anxiety.

Finally, a referral to a specialist clinic should be made in accordance with NICE guidelines, e.g. heart failure one-stop diagnostic clinics, respiratory physiotherapists, if the underlying cause of the breathlessness cannot be established, if the symptoms are disproportionate to the severity of their disease, if there is an unexpected response to therapy, if the patient would benefit from multidisciplinary services not available in primary care, and where further tests are indicated to stage and treat a diagnosed cause.

This algorithm has a strong evidence base and is the considered judgement of the IMPRESS/London School of Economics team following an extensive project on breathlessness. Given the lack of data on

110 For the Impress algorithm pathway and explanation, see: http://www.networks.nhs.uk/nhs-networks/impress- improving-and-integrating- respiratory/documents/Breathlessness%20algorithm%20IMPRESS%20LSE%20HEalth%20Foundation%20FIN AL.pdf/view

61 cost-effectiveness, the team have worked up the algorithm de novo, including a very extensive literature review. 45 people have commented on the pathway, including two national clinical directors. Although no formal rollout programme has been agreed, the algorithm is currently being tested in two settings (Southwark and Bradford). As the algorithm shows, the pathway does not depend upon any major reconfiguration of services but places a focus on precision at each step in the pathway.

New models of diagnostic care for breathlessness: pathways

The only comprehensive pathway that has been published for new models of diagnostic care is that for NHS Ashton, Leigh and Wigan.111. Two illustrations of pathways are provided: ‘breathlessness diagnostic future state care pathway’ and ‘diagnostic protocol: diagnostic service. Breathless patients aged >40 with signs/symptoms of heart failure and/or previous ischaemic heart disease/diabetes’.

The first sets out the pathway for the improved diagnosis of patients through the introduction of a One Stop Shop to aid diagnosis of the causes of breathlessness. It focuses on breathlessness patients presenting in primary care where there is diagnostic uncertainty, defined as patients aged >50 with a past medical history of ischaemic heart disease or diabetes in primary care. The algorithm shows that the GP will refer the patient for blood tests and chest X-ray in secondary care and will then arrange an appointment with the patient to review results. On receipt of the blood tests and chest x-ray the GP will then refer the patient into the diagnostic One Stop Shop, which will be responsible for taking a history and doing the tests in an appropriate sequence: spirometry with reversibility 1 x 20 minutes PC, BNP, Echocardiogram, and ECG (20 minutes). This sequence reflects firstly excluding heart failure where this is a possibility: if heart failure is a possibility (that is, if BNP is raised) an echocardiogram will be performed which will be interpreted by a cardiologist, who will prepare a management plan which may exclude the need for an outpatients appointment. If a diagnosis cannot be given (estimated 10% of patients), the patient will be referred for a new outpatients appointment. If a diagnosis can be given (90% of patients), there may be a need for a new outpatients appointment in an estimated 15% of cases but probably primary care management in 85%.

The second illustrates the pathway schematically, highlighting the criteria for the service (chest x-ray for all-patients with breathlessness and who are smokers aged > 40 years and routine bloods including fibromyalgia symptoms (FMS), not anaemic). It shows how interpretations of BNP and the ECG may lead to GP care or a referral to a respiratory consultant or cardiology outpatients department.

Papworth Direct One Stop Service Breathlessness Pathway

Papworth Direct is an assessment centre for patients with suspected angina, murmurs, palpitations and breathlessness that has published a One Stop Service breathlessness pathway112. In the pathway the patient presents at the GP surgery with shortness of breath, reduced exercise tolerance, fatigue,

111 Ashton, Leigh and Wigan NHS. Practice Based Commissioning. Patient Focus/Atherleigh Consortium. Proposal for Commissioning Plan for Breathlessness. V6.6. The proposed pathway is set out in the diagrams on p. 40 and 41. See: http://www.alpfhealth.org.uk/docs/breathlessness.pdf 112 Papworth Hospital NHS Foundation Trust. Papworth Direct One Stop Service- Breathlessness Pathway. Accessed at: http://www.papworthdirect.nhs.uk/pdfs/Papworth-Direct-One-Stop-Service-Breathless- Pathway.pdf

62 peripheral oedema, orthopnoea, and paroxysmal nocturnal dyspnoea. The GP should take a history, do an examination, blood tests for U and Es, FBC, thyroid function tests (TFTs), glucose, lipids and BNP (if available), peak flow, and ECG. Optional but advisable are chest x-ray and ECHO to differentiate between pulmonary and cardiac disease. The ECG, chest x-ray and ECHO are available as open access tests via Papworth Direct to aid GP diagnosis.

Patients are referred to Papworth Direct for either open access tests or a pathway. GPs are required to fax a referral form together with any test results to the booking office. The GP indicates on the referral form whether they are referring the patient for direct access tests only (ECG, CXR, Echo, 24/48 hr tape) or for referral for pathway (suspected angina, murmur, palpitation, breathlessness); past medical history; risk factors; current medication; clinical examination (for pathways); bloods; patient’s physical ability to undergo an exercise test; then sections on the four main symptom areas including breathlessness.

For pathway patients only the form can be attached to the Choose and Book referral. This should happen on the same day as seeing the patient. It is clearly a rapid access service. The patient is asked to phone the One Stop Service the afternoon of the day after the GP has seen them, to give time for the referral form to reach the One Stop Service and be reviewed by the medical specialist. A date is then booked for their Papworth Direct appointment. On arrival at Papworth Direct, the patient is initially seen by the medical specialist of the day who will take a history, examine the patient, and explain the planned investigations. All patients referred into the breathlessness pathway will have a repeat ECG, chest x-ray if not previously done, ECHO, spirometry and O2 saturation. Some patients will also be asked to do an exercise treadmill test.

Following completion of all the required tests, the patient has a consultation with the medical specialist who then decides the treatment plan. The Breathlessness Pathway shows three options under referral indicators: Results normal and heart failure unlikely: reassure and consider alternative diagnosis; results abnormal and heart failure likely. Treatment may be started to control symptoms with angiotensin-converting-enzyme (ACE) inhibitor and diuretic: refer to Papworth Direct; If pulmonary disease is suspected: refer to Quick Access Chest Clinic. The patient will then see the nurse again before they leave to check any queries are answered and a letter summarising the treatment plan will be given to the patient, with another copy and all of the results being sent to the patient’s GP.

In summary, there is no filtering of patients before referral (the Wigan, Ashton and Leigh pathway for referral to the One Stop Shop was for patients where there was diagnostic uncertainty). Moreover, the one stop shop in the Papworth Breathlessness Pathway is prepared to undertake most of the diagnostic tests113. In addition to the direct access diagnostic tests, patients can also be referred into a ‘package

113 Investigations for heart failure undertaken in the Breathlessness Pathway include: - ECG – may suggest underlying ischaemic basis for heart failure but can also indicate other possible pathologies e.g. hypertension, hypertrophic cardiomyopathy, arrhythmia. - CXR – Cardiomegaly and other signs of heart failure may confirm the diagnosis, but can also look for evidence of e.g. lung disease, hiatus hernia. - Bloods – Important to exclude thyroid, renal disease, anaemia and diabetes. - Coronary angiography/CT angiography – often necessary to exclude significant coronary disease / ischaemia as a cause of heart failure and can also give an indication of cardiac function. - Echocardiography – Provides information not only about systolic function but also diastolic function and can exclude more unusual causes of heart failure e.g. restrictive, constrictive and hypertrophic cardiomyopathies, cardiac tumours, pericardial effusions.

63 price’ pathway (the pathways are angina, palpitations, murmur, and breathlessness) which will include various tests, as determined by the pathway and medical specialist, followed by a consultation to commence treatment or determine their ongoing management plan.

Suspected new heart failure heart failure patient diagnostic pathway.

Developmental work has been undertaken on new diagnostic pathways for heart failure in Scotland114. The Diagnostic Pathway for heart failure in fig. 1 (below) is being piloted in Victoria Infirmary (for GPs in SE Glasgow Community Health Partnership area). It is designed so that patients with suspected heart failure are given a rapid and accurate diagnosis and management plan, and includes the use of BNP tests as a definite ‘rule out’ for patients that have a normal ECG. Once the pilot has been evaluated, it is the intention to roll it out across Greater Glasgow and the Clyde.

- Cardiac MRI – may be used to obtain more detailed information about cardiac anatomy, size and function. Used in heart failure in congenital heart disease and to study hibernating myocardium in ischaemic cardiomyopathy. - Exercise testing – may be useful to assess ischaemic cardiomyopathy, exercise tolerance, improvement to treatment and can provide prognostic information. Cardiopulmonary exercise testing is performed as part of the advanced heart failure and transplant work-up.

114 NHS Scotland and the Scottish Government Health Delivery Directorate Improvement and Support Team. Long Term Conditions Collaborative. Improving Care Pathways. Edinburgh: The Scottish Government, 2010.

4. Discussion and Conclusions

This scoping research on models of care to support earlier diagnosis of diseases related to breathlessness as a symptom focused on four research questions. With respect to the first – what evidence or good practice exists on early diagnosis and its impact on the quality of patient care and costs to the health service – there was a clear dearth of evidence but some relevant examples (for example, the lung investigation day). A search for literature focusing specifically on patient experience yielded useful findings only for COPD, lung cancer and asthma.

With respect to research questions 2 and 3, there was more extensive evidence, evaluation, and/or models for diagnosis of disease from a symptom-based perspective. Models, standards, and good practice were reviewed for ‘rapid’ access to diagnostics clinics, including rapid access clinics for chest pain, palpitations, arrhythmia and atrial fibrillation, and murmur. With respect to the rapid access clinic model in general, there is a need for more research on the effectiveness of different organisational arrangements, on clinical outcomes, continuity of care, and costs.

The evidence base on some of these rapid access clinics is limited, with only one or two substantive studies, so it is difficult to draw relevant findings for breathlessness clinics. For example, we do not know how many rapid access clinics for arrhythmia/atrial fibrillation there are in the United Kingdom (UK) and most of our knowledge relates to just one clinic (Charing Cross, set up in 2002). Data for this clinic is limited to patient throughputs and diagnostic yield, with no cost-effectiveness data.

With respect to rapid access palpitations clinics, again the evidence is limited to one substantive study with limited information on how referrals are made to the RAPC (including self-referral), what determines these referrals, how many RAPCs there are in the UK, and the benefits/drawbacks of integrating these various symptom-based clinics.

Nevertheless, these rapid access clinics offer some important findings with respect to constancy in diagnostic yield, equity of access, and substitutability. They offer sufficient evidence for this review to recommend that there should be national standardisation of data collection and a computerised database at all clinics to assist with local management and the central collection and analysis of performance data aimed at monitoring and optimising management. The review also recommends the need to increase public awareness of the symptoms of breathlessness more widely than in the current pilot of two northern towns.

With respect to the fourth research question, only a few models of breathlessness clinics were identified in the literature and several of these were still in development. There are no patient outcomes or robust cost-effectiveness data for any of these models. Independent evaluation is needed to compare costs and benefits of different service configurations. However, the lack of such data should not stall the introduction of rapid access breathlessness clinics or new diagnostic pathways as these are likely to be tailored to local circumstances and needs.

The models identified fall within the two organisational types identified by IMPRESS: i) a federated model, with each general practice providing a core service, and then referring to a triage or primary care practitioner with a special interest; ii) a breathlessness assessment service commissioned from a local hospital, that has diagnostic equipment such as echocardiography and chest X-ray on site. Most fall within the latter category and are based on the rapid access one stop shop model. There are some commonalities: Chelsea and Westminster and North Staffs are similar in being developed as joint

65 initiatives by cardiologists/respiratory clinicians, perhaps providing an opportunity for collective learning. Further, some of the models select for patients where there is diagnostic uncertainty, while others do not filter patients.

The IMPRESS algorithm is currently the only available evidence-based pathway, to which reference should be made in new model and diagnostic pathway development.