Volume 27 No. 3
Autumn 2017
Gastroenterology Today In this issue Irritable Bowel Syndrome...Can Psychological Treatments Help? Coeliac Disease Irritable Bowel Syndrome... What Roles for The Experts
Are your patients taking the right dose?
✓ Monitor: Think about the dose of Creon® your patients are taking and review their symptoms regularly.
✓ Dosing: If the treatment is not successful, consider For the titrating up their dose. treatment of pancreatic ✓ Reduce pill burden: If patients are still symptomatic or exocrine require more than 100,000 lipase units per meal, consider insufficiency titrating up to a higher strength using Creon® 40,000. Creon Micro Pancreatin 60.12 mg Gastro-resistant Granules, Creon 10000 Capsules, Creon 25000 Capsules, Creon 40000 Capsules: PRESCRIBING INFORMATION
Presentation: Creon Micro: Gastro-resistant granules of pancreatin, containing in 100mg: 5,000 PhEur units of lipase; 3,600 PhEur units of amylase; 200 PhEur units of protease. Creon 10000: Each capsule contains pancreatin equivalent to: 10,000 PhEur units of lipase; 8,000 PhEur units of amylase; 600 PhEur units of protease. Creon 25000: Each capsule contains pancreatin equivalent to: 25,000 PhEur units of lipase; 18,000 PhEur units of amylase; 1,000 PhEur units of protease. Creon 40000: Each capsule contains pancreatin equivalent to: 40,000 PhEur units of lipase; 25,000 PhEur units of amylase; 1,600 PhEur units of protease. Indication: Pancreatic exocrine insufficiency. Dosage and Administration: Creon Micro: Initially 100mg (5000 lipase units) taken with each feed or meal or immediately after. The required quantity of granules should be dispensed using the measuring scoop provided which holds 100mg. In young infants, mix with a small amount of (undiluted) apple juice and give from a spoon directly before the feed. In weaned infants, mix with acidic liquids or soft foods (e.g. undiluted apple juice or apple puree) and take directly before the meal without chewing. Alternatively, mix the granules with a small amount of milk on a spoon and administer to the infant immediately. The granules should not be added to the baby’s bottle. Creon 10000, 25000 and 40000: Initially one or two capsules during or immediately after meals, then adjust according to response. The capsules can be swallowed whole, or for ease of administration they may be opened and the granules taken with acidic fluid or soft food, but without chewing. This could be apple sauce or yoghurt or any fruit juice with a pH less than 5.5, e.g. apple, orange or pineapple juice.
Job code:CRE-2017-0109 Date of preparation: April 2017
Creon Micro, 10000, 25000 and 40000: Dose increases, if required, should be added slowly with careful monitoring of response and symptomatology. Maximum daily dosage of Creon Micro should not exceed 10,000 units lipase/kg/day. Ensure adequate hydration. If the granules are mixed with fluid or food, it is important that they are taken immediately and the mixture not stored, otherwise dissolution of the enteric coating may result. In order to protect the enteric coating, it is important that the granules are not crushed or chewed. Crushing and chewing of the minimicrospheres or mixing with food or fluid with a pH greater than 5.5 can disrupt the protective enteric coating. This can result in early release of enzymes in the oral cavity and may lead to reduced efficacy and irritation of the mucous membranes. Care should be taken to ensure that no product is retained in the mouth. Colonic damage has been reported in patients with cystic fibrosis taking in excess of 10,000 units of lipase/kg/day (see below). Contraindications, Warnings etc: Hypersensitivity to pancreatin of porcine origin or any excipients. Fibrosing colonopathy has been reported in CF patients taking high dose pancreatin preparations. As a precaution, medically assess unusual or changes in abdominal symptoms, especially for doses above 10000 units of lipase/kg/day. Pregnancy and Lactation: There is inadequate evidence of safety in use during pregnancy. Pancreatic enzymes can be used during breast-feeding. Ability to Drive and Operate Machinery: No or negligible influence on ability. Side Effects: Most commonly, gastrointestinal disorders. Common: nausea, vomiting, constipation, diarrhoea and abdominal distension. Gastrointestinal disorders are mainly associated with the underlying disease. Similar or lower
incidences compared to placebo were reported for abdominal pain (very common, ≥1/10). Uncommon: rash. Frequency unknown: Hypersensitivity (anaphylaxis), pruritus and urticaria, strictures of the ileo-caecum and large bowel (fibrosing colonopathy). See SPC for further information. Interactions: no studies performed. Name and Address of Marketing Authorisation Holder: Mylan Products Ltd., 20 Station Close, Potters Bar, Herts, EN6 1TL PL No: Creon Micro: PL 46302/0031, Creon 10000: PL 46302/0028, Creon 25000: PL 46302/0029, Creon 40000: PL 46302/0030 Basic NHS price: Creon Micro (20g): £31.50, Creon 10000 (100 capsules): £12.93, Creon 25000 (100 capsules): £28.25, Creon 40000 (100 capsules): £47.55 Legal Category: Creon Micro and Creon 10000: P, Creon 25000 and Creon 40000: POM Further information is available in the UK from: BGP Products Ltd., Building Q1, Quantum House, 60 Norden Road, Maidenhead, SL6 4AY Date of Last Revision: 29/03/2017 Adverse events should be reported.Reporting forms and infomation can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Mylan by phone 0800 121 8267 or email ukpharmacovigilance@mylan.com.
CONTENTS
CONTENTS 5
EDITORS COMMENT
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FEATURE I BS: Can psychological treatments help?
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FEATURE C oeliac disease
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FEATURE I rritable Bowel Syndrome
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FEATURE S upport the Back Pain Plus Campaign
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NEWS
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BSG POSTERS
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COMPANY NEWS
COVER STORY A NEW ‘TEST AND REFER’ STRATEGY FOR PRIMARY CARE Experts agree that by targeting endoscopy resources towards those patients with the greatest risk it is possible to diagnose diseases sooner and deliver major improvements in survival in a cost-effective way.1 Selecting appropriate dyspeptic patients for referral from a primary care setting can be difficult based on symptom presentation alone, and so endoscopy services are often oversubscribed with poor diagnostic yields. Atrophic Gastritis (AG) is a high-risk, chronic inflammatory condition of the gastric mucosa that is caused by Helicobacter pylori infection or autoimmune disease. This pre-neoplastic condition is considered the most important risk factor for Gastric Cancer (GCa) with 18% of AG cases progressing to cancer within 10 years.2
GastroPanel® accurately identifies AG from a single blood sample and is recommended as the first-line diagnostic test for adult dyspeptic patients in Primary Care in order to identify at-risk patients in whom gastroscopy should be recommended. The GastroPanel® blood test is manufactured by BIOHIT HealthCare, a Finnish company that specialises in the screening, diagnosis and monitoring of GI diseases. Tel: +44 (0)151 550 4 550 info@biohithealthcare.co.uk www.biohithealthcare.com/uk
This issue edited by: Dr M Goldman BSc, MBBS, MRCP, FFPM c/o Media Publishing Company Media House 48 High Street SWANLEY, Kent BR8 8BQ ADVERTISING & CIRCULATION: Media Publishing Company Media House, 48 High Street SWANLEY, Kent, BR8 8BQ Tel: 01322 660434 Fax: 01322 666539 E: info@mediapublishingcompany.com www.MediaPublishingCompany.com PUBLISHING DATES: February, June and October. COPYRIGHT: Media Publishing Company Media House 48 High Street SWANLEY, Kent, BR8 8BQ PUBLISHERS STATEMENT: The views and opinions expressed in this issue are not necessarily those of the Publisher, the Editors or Media Publishing Company. Next Issue Spring 2018 Subscription Information – Autumn 2017 Gastroenterology Today is a tri-annual publication currently sent free of charge to all senior qualified Gastroenterologists in the United Kingdom. It is also available by subscription to other interested individuals and institutions. UK: Other medical staff - £18.00 inc. postage Non-medical Individuals - £24.00 inc. postage Institutions Libraries Commercial Organisations - £48.00 inc. postage Rest of the World: Individuals - £48.00 inc. postage Institutions Libraries Commercial Organisations - £72.00 inc. postage We are also able to process your subscriptions via most major credit cards. Please ask for details. Cheques should be made payable to MEDIA PUBLISHING. Designed in the UK by Hansell Design
Dinis-Ribeiro M. et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012 January ; 44(1): 74–94.
1
Whiting J. et al. The long term results of endoscopic surveillance of premalignant gastric lesions. Gut 2002;50:378–381.
2
GASTROENTEROLOGY TODAY - AUTUMN 2017
By reconfiguring patient pathways to identify dyspeptic individuals with AG in a Primary Care setting, GPs are able to select those patients at greatest risk for referral. All that is required is a simple blood test called GastroPanel®.
Gastroenterology Today
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EDITORS COMMENT
EDITORS COMMENT Brexit I voted to join the common market when I was a medical student, but what I voted for was something to do with free trade and movement of goods, or so I thought. I write this editorial, in the aftermath of a speech by our leader in Firenze, and I am left mind-numbingly confused as to whether we will be in or out, and if we are out, as 51.9% of the population voted, surely that means out. I do not wish to fly any political flags here, but I think there are very few readers who will have practiced medicine in this country before EC (you see I have changed the terminology) membership. It is a bit confusing as to what the changes will mean for medicine, as the public details are a bit vague. We suspect that there may not be free movement of labour (but maybe there will), and the mutual recognition of medical qualifications may be erased. It is clear that there needs to be guidance what will work after 2019 (I think that is the current date) and who will be employable. I am guessing that medical manpower has thought about this, but there is little clarity. According to the King’s Fund “Approximately 60,000 of the 1.2 million NHS workforce are from other EU (another change of terminology) countries, including more than 10,000 doctors and more than 20,000 nurses and health visitors. In adult social care, 90,000 of the 1.3 million workers employed by local authority and independent sector employers come from elsewhere in the EU. The current policy of free movement remains unchanged until the UK concludes the terms of its exit from the EU. Despite this, there is evidence that Brexit is having an impact. The number of EU nationals registering as nurses in the UK has fallen by 96 per cent since the referendum, with just 46 EU nurses registering with the Nursery and Midwifery Council in April 2017. There has also been a fall in the number of EU nationals taking jobs in the social care sector.” Presumably this will need a granular change process so that a health service can be maintained, and a relevant set of standards will be necessary to ensure that the education and practical training match local expectations. Maybe revalidation may actually prove to be of some use. A more mysterious issue will be the access to medicines and medical devices so loved by gastroenterologists. At the moment, new medicines are typically centrally authorised by the London-base European Medicines Agency and then locally in this country by MHRA. It seems certain that the EMA would move its headquarters out of London to an EU country. Some in the pharma world argue that this will in itself reduce the importance of this country in the eyes of the global drug companies. If the UK decides to negotiate to stay in the EEA (Oh dear, another term!) there would not, in practice, be much difference to regulation. But if the UK stays out of the EEA, drug companies would need to go through a separate process with British regulators for new products as the centralised European route would not be applicable to the UK. It is possible that like some other European non-EU, the UK may sign up to abide by the decisions, but it will no longer be part of the decision making process. The information about medical devices is speculative at the time of writing. In the short term, it has been confirmed that business can continue like usual, and the free movement of goods between the members of the EU can also continue. This means that products and machines being placed on the market in the UK (and the rest of the EU) will still be required to be CE marked as appropriate. It is more difficult to say what could happen in the long term, as it will depend upon what will be negotiated within or after the ‘Article 50’ process for the UK to leave the EU. However, it is important to remember that the Leave campaign still wish to trade with the EU and given that the CE Marking Directives are implemented into UK law, it is likely that CE marking will still remain a requirement for UK manufacturers. Theresa May at the Conservative Party Conference at the start of October 2016 said that when the European Communities Act is repealed the acquis (the existing body of EU Legislation) into British law. These UK laws will then only be amended when they have been subject to full scrutiny and proper Parliamentary debate. The key message is that the same rules and laws apply and therefore it is presumed that the same will apply for CE Marking Legislation for UK Manufacturers, Importers and Distributors. However it is not clear how much of this is wishful thinking by trade organisations. I wish I could say something clear and meaningful, but I am at a loss. Time will tell, and one thing is apparent to me: there will be pain and confusion for all.
GASTROENTEROLOGY TODAY - AUTUMN 2017
“The number of EU nationals registering as nurses in the UK has fallen by 96% since the referendum, with just 46 EU nurses registering with the Nursery and Midwifery Council in April 2017. There has also been a fall in the number of EU nationals taking jobs in the social care sector.”
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FEATURE
IRRITABLE BOWEL SYNDROME: CAN PSYCHOLOGICAL TREATMENTS HELP? Dr Andrew David Dainty, lecturer, registered nurse and researcher working within the College of Health and Social Care at the University of Derby, talks about Irritable Bowel Syndrome and whether psychological treatments can help the common, long-term condition.
What is Irritable Bowel Syndrome? The Irritable Bowel Syndrome, more commonly known as IBS, is a functional gastrointestinal complaint which usually results in a range of unpleasant symptoms. The term ‘functional’ relates to the fact that although the bowel doesn’t seem to function as well as it perhaps should, there is usually no physiological cause for symptoms. That’s to say, that blood tests and samples taken by doctors usually reveal no abnormality. Symptoms range from chronic and persistent diarrhea to chronic or intermittent constipation. People with IBS also experience various levels of chronic or intermittent abdominal pain and alternating bowel habits which often seem unrelated to diet or lifestyle and can be troublesome to control. Interestingly, people with IBS also experience much more anxiety and depression compared to people without IBS. Unfortunately, this often leads to stigma surrounding IBS and other medically unexplained symptoms and people are sometimes told that symptoms are ‘in their heads’ or not real.
Who suffers from IBS? IBS is more common in women than men, with a ratio of about 2:1. It’s unclear why this so. IBS is more frequently reported during the third and fourth decades of life. Around 14% of women and 6% of men will experience IBS at some point in their lives. GASTROENTEROLOGY TODAY - AUTUMN 2017
Is IBS easy to manage? The symptoms of IBS can look very much like symptoms associated with other gastrointestinal problems such as coeliac disease (a condition relating to an intolerance to gluten) or some inflammatory conditions. Therefore, doctors often check for other conditions which can cause symptoms much like those experienced by people with IBS before making an IBS diagnosis. IBS is sometimes challenging for healthcare professionals, as many people fail to gain relief from the medicines prescribed by in efforts to curtail symptoms. Around 4 out of 10 individuals will still be experiencing IBS ten years after being diagnosed with the condition, which demonstrates that for some, IBS can become a chronic and persistent problem.
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Can psychological treatments help? I feel extremely privileged to have spent a number of years studying IBS, and led a research study looking into the feasibility of a type of psychological treatment for the condition while studying during a PhD fellowship. Why would one use psychological treatments for a condition largely relating to the bowel you might reasonably ask? One of the challenges that people with IBS face, is the lack of effectiveness of some of the medical treatments available. Coupled with the fact that people with IBS often face a great deal of stigma and experience a poorer quality of life, it’s not too difficult to see why some people have a real tough time trying to live with the condition. The aim of the research I have been doing focuses on using a type of psychotherapy called Cognitive Behavioural Therapy (CBT). The aim of using this type of treatment is to help people with IBS live more fulfilling lives and deal with some of the problems brought about by their IBS. IBS affects people in a variety of ways and it’s been quite an insight to spend time with people who experience these problems and learn how much of an impact IBS really has upon people and their lives. It isn’t unusual for people to stop going places they once did or to not engage in the activities and pastimes they once enjoyed. CBT helps people to find ways of combatting some of these problems using a variety of evidence based techniques. CBT treatment is now becoming much more accessible to people, particularly for common mental health problems such as anxiety and depression thanks to a variety of government investments in mental health service provision. However, there are few therapists who specialise in using CBT to treat IBS and these treatments are not used routinely within the NHS for IBS. I would say that although it is not true that IBS is ‘all in the head’, an interesting thing about IBS is that some studies have shown that psychological treatments like CBT also seem to help improve the physical symptoms of IBS. The research I have been working on aims to evaluate whether a low-intensity type of CBT treatment could be delivered by trained nurses within NHS hospitals. The research shows that the intervention was potentially feasible and we learned a great deal about how people experience this kind of intervention. After carrying out interviews with people who experienced various CBT treatments within the study, we now have more information on what might be required to make these types of treatment more acceptable and relevant to people who might choose this approach.
FEATURE
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FEATURE
COELIAC DISEASE Coeliac disease is a lifelong autoimmune disease associated with
functional hyposplenism, nutritional deficiencies and in rare cases,
chronic inflammation of the small intestine. Coeliac disease affects
intestinal malignancy [7].
one in 100 people in the UK and while the rate of diagnosis for coeliac disease has improved over recent years, it remains low with
In addition to maintaining adherence to the diet, it is important that
only 24% of those with the condition benefiting from a diagnosis
patients are supported to ensure that their diets are nutritionally
[1]. Rates of diagnosis are also known to vary by socio-economic
adequate. Data from the National Diet and Nutrition Survey shows
status, with children living in more deprived areas in the UK less likely to be diagnosed [2]. The symptoms of coeliac disease vary between individuals and the National institute of Health and Care Excellence (NICE) has listed the most common symptoms where serological testing should be carried out. The symptoms listed include persistent unexplained abdominal or gastrointestinal symptoms, prolonged fatigue, unexpected weight loss (although not in all cases), severe or persistent mouth ulcers and unexplained iron, B12 or folate deficiency. In children, faltering growth can also be a symptom.
that cereals and cereal products contribute 44% of total iron intake and 30% total calcium intake to the diet [8]. The complete removal of cereals therefore needs to be carefully managed particularly as calcium recommendations are higher (1000 mg/day) for people with coeliac disease compared to the general population (700 mg/day) [9]. Including good sources of calcium in the diet is therefore especially important for people with coeliac disease. Coeliac UK is the national charity helping people living without gluten to live happier, healthier lives. For nearly 50 years we have been the experts on coeliac disease and the gluten free diet, providing our
It is unsurprising that nutritional deficiencies are common in
members with advice and support, funding critical research into coeliac
undiagnosed coeliac disease due to the damage to the lining of the
disease and fighting for better availability of gluten free food.
gut caused by gluten ingestion. Iron deficiency anaemia is particularly common, with 30-50% of patients having iron deficiency anaemia at
To stay up to date on the latest developments in coeliac disease and the
diagnosis [3].
gluten free diet, including free CPD resources and access to materials to help support your patients, join our free healthcare professional
The gastrointestinal symptoms of coeliac disease such as diarrhoea,
network at: https://www.coeliac.org.uk/join-us/hcp/
cramping, bloating, wind and constipation are similar to those of irritable bowel syndrome (IBS) and NICE recommends that coeliac disease should be excluded before diagnosing a patient with IBS. Despite this, misdiagnosis with IBS is common and one in four people with coeliac disease have previously been treated for IBS [4]. Coeliac disease can be asymptomatic and NICE recommends that certain patient groups who are at a higher risk of coeliac disease are also tested, including: • type 1 diabetes, at diagnosis • autoimmune thyroid disease, at diagnosis
The only treatment available for coeliac disease is lifelong adherence to the gluten free diet but the diet can be difficult to follow and rates of adherence have been found to vary between 42 – 91% [5]. Gluten is a protein found in the cereals wheat, barley and rye and is present in many staple foods including bread, pasta, breakfast cereals and flour. Gluten is also “hidden” in many other foods such as soy sauce, soups, sausages and ready meals. Recent research published in August 2017 has identified a number of factors associated with improved adherence to the diet, including membership of Coeliac UK, understanding food labels, receiving gluten free food on prescription and liking the taste of gluten free foods [6]. Supporting adherence to the diet is important to minimise the risk of long term complications including osteoporosis, ulcerative jejunitis,
dermatitis herpetiformis in the UK over two decades: population-based study. Am J Gastroenterol, 2014. 109(5): p. 757-68. 2. Zingone, F., et al., Socioeconomic variation in the incidence of childhood coeliac disease in the UK. Arch Dis Child, 2015. 3. Ludvigsson, J.F., et al., Use of computerized algorithm to identify individuals in need of testing for celiac disease. J Am Med Inform Assoc, 2013. 20(e2): p. e306-10. 4. Card, T.R., et al., An excess of prior irritable bowel syndrome diagnoses or treatments in Celiac disease: evidence of diagnostic delay. Scand J Gastroenterol, 2013. 48(7): p. 801-7. 5. Hall, N.J., G. Rubin, and A. Charnock, Systematic review: adherence to a gluten-free diet in adult patients with coeliac disease. Aliment Pharmacol Ther, 2009. 30(4): p. 315-30. 6. Muhammad, H., et al., Adherence to a Gluten Free Diet Is Associated with Receiving Gluten Free Foods on Prescription and Understanding Food Labelling. Nutrients, 2017. 9(7). 7. NICE, NG20 Coeliac disease; recognition, assessment and management. 2015. 8. Henderson, L.I., K.; Gregory, J.; Bates, C.J.; Prentice, A.; Perks, J.; Swan, G.; Farron, M.;, , The National Diet & Nutrition Survey: adults aged 19 to 64 years vitamin and mineral intake and urinary analytes. 2003. 9. Ludvigsson, J.F., et al., Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut, 2014. 63(8): p. 1210-28.
GASTROENTEROLOGY TODAY - AUTUMN 2017
• first-degree relatives of people newly diagnosed with coeliac disease
1. West, J., et al., Incidence and prevalence of celiac disease and
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FEATURE
IRRITABLE BOWEL SYNDROME In the Age of Self-Management and “Dr Google”, what role for the experts? Irritable bowel syndrome describes a group of symptoms which consistently arise together. Whilst it is characterised by the absence of well-defined symptoms and investigation results, in the absence of sinister pathology, the Rome criteria, which are used to define it, have refined the diagnostic measures a number of times. Indeed the latest iteration of the Rome criteria, (Rome IV), significantly reduced the number of patients meeting the diagnostic criteria. However, they have at the same time attempted to bring diagnostic criteria into line with the current scientific understanding of the pathogenesis. Several mechanisms are involved in the genesis of symptoms, including disturbances in motility, visceral hypersensitivity, altered mucosal and immune function, altered microbiota and abnormal central nervous system processing. Within an individual patient several mechanisms may coexist, making clear elucidation of causation challenging. Whilst a number of experts have attempted to develop clear diagnostic pathways and investigations to guide treatment, the appropriate treatment for individual patients often eludes practising clinicians and their patients. This often
count, C reactive protein or erythrocyte sedimentation rate and antibody testing for coeliac disease. Whilst not recommended in the current NICE guidance, consideration should be given to stool testing for calprotectin and faecal elastase. Many patients spend considerable time before a firm diagnosis is reached, yet this is one of the few things that doctors have to offer.
An Overview of the treatments available Whilst all of the available treatments can be found on ‘Dr Google’ it is difficult for patients to decide which ones are evidence based or likely to work for them and which ones are a waste of money, or worse, may cause them potential harm. Doctors, gastroenterologists, dietitians and other professionals have the training and experience to be able to assess the evidence and sort fact from opinion. Professionals also have the ability to give a broad overview of all the available treatments and whilst many have their individual areas of expertise all should be able to guide patients to the help most appropriate to them. The relationship between patients and their healthcare professionals should enable the patient to access the treatment most suitable for them and fits with their lifestyle.
Professional distance or close compassion
leads to both clinician and patient feeling frustrated and despondent. Professionals often struggle to balance the two. We need to be able to Set within this background the NICE guidance makes clear “People
remain objective enough to use our scientific understanding to define
with IBS should be given information that explains the importance of self-
which treatments are likely to help our patients. Simultaneously patients
help in effectively managing their IBS. This should include information
often present with significant psychological distress, both because of
on general lifestyle, physical activity, diet and symptom-targeted
their symptoms and sometimes their drivers.
medication.” There is no question that all of these interventions may have positive effects on the symptoms of irritable bowel syndrome, but
We need to offer treatments based upon rational understanding of
is often challenging in the setting of a relatively short appointment to
disease processes but also compassion and sympathy to patients in
elucidate clearly which changes are right for an individual patient. As
distress. In addition we need to empower patients to take control of their
a consequence, clinicians and patients sometimes feel as if they are
lives and make the necessary changes that will enable them to manage
left ‘fumbling in the dark’ and patients may embark upon what is on
their symptoms.
occasion, a long, and at times, expensive journey to find the answers for GASTROENTEROLOGY TODAY - AUTUMN 2017
10
themselves.
Supporting Behaviour change
Patients seek help from a range of practitioners with varied success.
We know that patients are often keen to take control of their disease
Many resort to google and patient chatrooms where they receive advice and wisdom of variable quality and efficacy. This is also often the experience of those using the National Health Service. So what role for experts?
A firm Diagnosis
and to make the changes required to do this, but changing behaviour is often challenging. As healthcare professionals, we are often in a privileged position, we are allowed into the most private and personal aspects of people’s lives. That privilege comes with responsibility. We understand the challenges individuals face in ways that few others can. We therefore have a responsibility to support patients to make changes that may help their symptoms. Sometimes this is as ‘simple’ as encouraging them to eat breakfast. However, on occasion, more
The symptoms of irritable bowel syndrome are common to many other
complex dietary and psychological change is required. We are well
conditions and patients often have anxieties about what other conditions
placed to aid, support and on occasion challenge patients along their
they may have. Doctors have the training to elicit atypical symptoms and
individual journey, working alongside them to help individuals to find
‘red flags’. They also have access to diagnostic tests to exclude other
what works for them. Whilst we don’t always have a magic bullet, we
conditions and affirm the diagnosis. All patients should have a full blood
can always care.
FEATURE
SUPPORT THE BACK PAIN PLUS CAMPAIGN Authors & Affiliations: Dr Chong Seng Edwin Lim1 (Rheumatology Research Fellow), Dr Karl Gaffney1 (Consultant Rheumatologist) Corresponding Author: Dr Karl Gaffney, Norfolk and Norwich University Hospitals, Rheumatology Department, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY Email: karl.gaffney@nnuh.nhs.uk Phone: 01603 286765 Fax: 01603 287488
Axial spondyloarthritis
and 1% - 25% respectively (8,14,15,19–21). It has been shown that approximately 4% of patients with IBD present before the diagnosis of
Axial spondyloarthritis (axSpA) is a chronic inflammatory condition predominantly involving the spine and sacroiliac joints, with or without extra-spinal manifestations (ESM). ESM includes peripheral arthritis, enthesitis, iritis / anterior uveitis, psoriasis and inflammatory bowel disease (IBD) (1). AxSpA has a disease spectrum. This includes non-radiographic axSpA (nr-axSpA) – individuals with axSpA features but without established radiographic changes and Ankylosing Spondylitis (AS) – individuals with axSpA features and radiographic (X-ray) sacroiliitis (2).
AS and after twenty years, these percentages double to 7.5%. Also, there is a 3.3-fold risk of developing IBD in patients with AS compared to the general population (22,23). There is increasing evidence from genome-wide association studies of a relationship between AS and gut inflammation. Shared genetics may explain the close association, possibly contributing to a common inflammatory pathway (8,24). Increasing trend of HLA-B27 prevalence are being observed in patients with IBD, ranging from 9.6% with Inflammatory Back Pain, 40% with radiographic sacroiliitis, and 73% with
AxSpA is diagnosed clinically based on suspicious clinical features with supportive laboratory tests (Human Leucocyte Antigen B27 (HLA-B27), raised C reactive protein (CRP)) and imaging (MRI and/or X-ray). Advances in Magnetic Resonance Imaging (MRI) has enabled earlier diagnosis of axSpA via the identification of bone marrow oedema in the sacroiliac joints and/or spine prior to the development of structural changes on radiograph (3–5). A classification criteria for axSpA (see Figure 1) based on a
AS (25). The association of HLA-B27 in patients with both conditions (AS and IBD) is higher than the general population (no diagnosis of AS or IBD) but lower than in patients with only a diagnosis of AS. This suggests that being HLA-B27 positive can predispose to the development of sacroiliitis or AS in this population, but the association between AS and HLA-B27 in IBD is not a consistent finding (8) and HLA-B27 positivity is not needed in order to make a diagnosis of axSpA.
combination of imaging or clinical criteria in patients with chronic back pain with onset before 45 years of age has been established by the Assessment of SpondyloArthritis international Society (ASAS) (6,7). Figure 1 – ASAS Classification Criteria for Axial Spondyloarthritis (axSpA) (7) In patients with >3 months of back pain and age at onset < 45 years old Sacroiliitis on imaging * AND ≥1 SpA feature** ** SpA features:
HLA-B27 AND ≥2 other SpA features ** * Sacroiliitis on imaging:
• Active acute inflammation on MRI highly suggestive of sacroiliitis associated with SpA • Definite radiographic sacroiliitis according to modified New York criteria
Axial SpA typically begins in the 2nd and 3rd decade (26). Delay to diagnosis is a major problem with an average delay of between 8-10 years. This means that patients often endure intolerable symptom, linked to worse outcomes (disease activity, function, radiographic), despite the availability of effective new therapies (27). Early treatment offers the best chance of drug free remission and early disease responds best to TNF inhibitors (28,29). Sykes et al (30) have recently shown that the delay to diagnosis has not improved despite the advances in modern imaging and new approaches to diagnosis. They divided 1193 patients with a physician-verified diagnosis of axSpA into a historical (diagnosed pre-2009) and current cohort (diagnosed 2009-2013) and found that the mean delay to diagnosis in the historical cohort was 8.53 years, and 9.39 years in the current cohort. They concluded that there is still a need for further targeted education of health-care professionals in order to address the issue of delay to diagnosis. It is interesting to note that the subgroup analysis of the study showed that one predictor of a shorter delay to diagnosis is having a diagnosis of IBD (median delay 4.0 vs 6.0 years, P = 0.024; mean 6.45 vs 9.17 years, P = 0.012).
Gut-Joint Connection
Support Back Pain Plus!
Many prevalence studies show an association between axSpA and
In an attempt to address the problem of delay to diagnosis, the National
IBD, however the strength of this association is unclear. In patients with
Ankylosing Spondylitis Society (NASS) has developed the “BACK PAIN
AS, the prevalence of clinical IBD and/or subclinical gastrointestinal
PLUS” campaign which is an awareness campaign targeted at secondary
inflammation range from 3% - 10% to 25% - 69% (8–18). In patients
care specialist who manages patients with the common ESM of axSpA:
with IBD, the prevalence of axSpA or AS ranges from 4% - 7% (14,15)
acute anterior uveitis, IBD, and Psoriasis.
1
Rheumatology Department, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY
GASTROENTEROLOGY TODAY - AUTUMN 2017
• Inflammatory back pain • Arthritis • Enthesitis (heel) • Uveitis • Dactylitis • Psoriasis • Crohn’s/Colitis • Good response to NSAIDS • Family history for SpA • HLA-B27 • Elevated CRP
OR
Delay to diagnosis in axSpA
11
FEATURE It is proposed that these patients should be screened for the presence of chronic back pain (with inflammatory features) and referred to rheumatology if they are found to be screen positive. This may help uncover the “hidden burden” of axSpA in these population and facilitate appropriate assessment, thereby reducing the diagnostic delay and improve access to effective treatments. We therefore strongly encourage gastroenterologist to ask about back pain in IBD patients regardless of HLA-B27 status.
References
GASTROENTEROLOGY TODAY - AUTUMN 2017
12
1. Hamilton L, Barkham N, Bhalla A, Brittain R, Cook D, Jones G, et al. BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics. Rheumatology. 2017 Feb 1;56(2):313–6. 2. Keat A, Bennett AN, Gaffney K, Marzo-Ortega H, Sengupta R, Everiss T. Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents? Rheumatol Int. 2017 Mar;37(3):327–36. 3. Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):401–17. 4. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol. 2012 May;8(5):262–8. 5. Slobodin G, Eshed I. Non-Radiographic Axial Spondyloarthritis. Isr Med Assoc J IMAJ. 2015 Dec;17(12):770–6. 6. Rudwaleit M, Landewé R, Heijde D van der, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. 2009 Jun 1;68(6):770–6. 7. Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009 Jun;68(6):777–83. 8. Rudwaleit M, Baeten D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):451–71. 9. De F, Elewaut D, De M, De K, Cuvelier C, Mielants H, et al. Bowel inflammation and the spondyloarthropathies. Rheum Dis Clin N Am. 1998;24(4):785–813. 10. Leirisalo-Repo M, Turunen U, Stenman S, Helenius P, Seppälä K. High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum. 1994 Jan;37(1):23–31. 11. Vos MD, Cuvelier C, Mielants H, Veys E, Barbier F, Elewaut A. Ileocolonoscopy in Seronegative Spondylarthropathy. Gastroenterology. 1989 Feb 1;96(2):339–44.
12. Mielants H, Veys EM, Cuvelier C, De Vos M, Botelberghe L. HLA-B27 related arthritis and bowel inflammation. Part 2. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol. 1985 Apr;12(2):294–8. 13. Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys E. Histopathology of intestinal inflammation related to reactive arthritis. Gut. 1987 Apr;28(4):394–401. 14. de Winter JJ, van Mens LJ, van der Heijde D, Landewé R, Baeten DL. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a metaanalysis. Arthritis Res Ther. 2016 Sep 1;18:196. 15. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis. 2015 Jan;74(1):65–73. 16. Meuwissen SG, Dekker-Saeys BJ, Agenant D, Tytgat GN. Ankylosing spondylitis and inflammatory bowel disease. I. Prevalence of inflammatory bowel disease in patients suffering from ankylosing spondylitis. Ann Rheum Dis. 1978 Feb;37(1):30–2. 17. Brophy S, Pavy S, Lewis P, Taylor G, Bradbury L, Robertson D, et al. Inflammatory eye, skin, and bowel disease in spondyloarthritis: genetic, phenotypic, and environmental factors. J Rheumatol. 2001 Dec;28(12):2667–73. 18. Karreman MC, Luime JJ, Hazes JMW, Weel AEAM. The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis. 2016 Nov 4; 19. Salvarani C, Fries W. Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease. World J Gastroenterol WJG. 2009 May 28;15(20):2449–55. 20. Rodríguez-Reyna TS, Martínez-Reyes C, Yamamoto-Furusho JK. Rheumatic manifestations of inflammatory bowel disease. World J Gastroenterol WJG. 2009 Nov 28;15(44):5517–24. 21. Brakenhoff LKPM, Heijde DM van der, Hommes DW, Huizinga TWJ, Fidder HH. The joint—gut axis in inflammatory bowel diseases. J Crohns Colitis. 2010 Sep 1;4(3):257–68. 22. Stolwijk C, Essers I, van Tubergen A, Boonen A, Bazelier MT, De Bruin ML, et al. The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study. Ann Rheum Dis. 2015 Jul;74(7):1373–8. 23. El Maghraoui A. Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur J Intern Med. 2011 Dec;22(6):554–60. 24. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis-insights into pathogenesis. Nat Rev Rheumatol. 2016 Feb;12(2):81–91. 25. Palm O, Moum B, Ongre A, Gran JT. Prevalence of ankylosing spondylitis and other spondyloarthropathies among patients with inflammatory bowel disease: a population study (the IBSEN study). J Rheumatol. 2002 Mar 1;29(3):511–5. 26. The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients. - PubMed - NCBI [Internet]. [cited 2017 Aug 28]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=T he+national+database+of+the+German+Collaborative+Arthritis+Ce ntres%3A+I.+Structure%2C+aims%2C+and+patients 27. Seo MR, Baek HL, Yoon HH, Ryu HJ, Choi H-J, Baek HJ, et al. Delayed diagnosis is linked to worse outcomes and unfavourable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015 Aug;34(8):1397–405. 28. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Märker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 2009 Mar;60(3):717–27. 29. Sieper J, Heijde D van der, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with nonradiographic axial spondyloarthritis: results of a randomised placebocontrolled trial (ABILITY-1). Ann Rheum Dis. 2013 Jun 1;72(6):815–22. 30. Sykes MP, Doll H, Sengupta R, Gaffney K. Delay to diagnosis in axial spondyloarthritis: are we improving in the UK? Rheumatol Oxf Engl. 2015 Dec;54(12):2283–4.
FEATURE
AFTER 20 YEARS, A NEW APPROACH IN PBC1,2 Introducing OCALIVA OCALIVA offers a new option for patients with inadequately controlled PBC on UDCA or as monotherapy for those who are unable to tolerate UDCA1
Engage a new pathway
Proven efficacy
OCALIVA is a first-in-class selective and potent FXR agonist. FXR is thought to play a crucial role in bile acid homeostasis and pathways controlling inflammation
When OCALIVA was given in combination with UDCA,* almost 5 times as many patients achieved reductions in ALP and stabilisation of bilirubin levels at 12 months compared with UDCA alone.1† The effects of OCALIVA were sustained over an additional 12 months of therapy in
and fibrosis1,3
the open-label extension study4
OCALIVA is indicated for the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in combination with UDCA in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA.1 OCALIVA has a conditional licence. *UDCA was withheld from patients intolerant to UDCA.4 †35 patients receiving OCALIVA 10 mg + UDCA (48%) and 46 patients receiving OCALIVA titration + UDCA (46%) achieved the primary composite endpoint of ALP <1.67 x ULN with a ≥15% reduction from baseline and total bilirubin ≤ULN compared with 7 patients on placebo + UDCA (10%); UDCA was withheld from patients intolerant to UDCA.4 Abbreviated Prescribing Information OCALIVA® (obeticholic acid) (Please refer to the Full Summary of Product Characteristics (SmPC) before prescribing) response and tolerability. Paediatric population: No data. Contraindications: Hypersensitivity to the active substance or any excipients. Complete biliary obstruction. Special warnings and precautions for use: Liverrelated adverse events occurring as early as within the first month of treatment; elevations in alanine amino transferase (ALT), aspartate aminotransferase (AST) and hepatic decompensation have been observed and patients should be monitored during treatment with OCALIVA. Severe pruritus; see recommendations for dosage reduction and use of bile acid binding resins or antihistamines. Interactions: Following co-administration of warfarin and obeticholic acid. International normalised ratio (INR) should be monitored and the dose of warfarin adjusted, if needed, to maintain the target INR range. Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended. Obeticholic acid should be taken at least 4–6 hours before or after taking a bile acid binding resin, or at as great an interval as possible. Fertility, pregnancy and lactation: Avoid use in pregnancy. Either discontinue breast-feeding or discontinue/abstain from obeticholic acid therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. No clinical data on fertility effects.
Undesirable effects: Very common (≥1/10) adverse reactions were pruritus, fatigue, and abdominal pain and discomfort. The most common adverse reaction leading to discontinuation was pruritus. The majority of pruritus occurred within the first month of treatment and tended to resolve over time with continued dosing. Other commonly (≥ 1/100 to < 1/10) reported adverse reactions are, thyroid function abnormality, dizziness, palpitations, oropharyngeal pain, constipation, eczema, rash, arthralgia, peripheral oedema, and pyrexia. Overdose: Liver-related adverse reactions were reported with higher than recommended doses of obeticholic acid. Patients should be carefully observed and supportive care administered, as appropriate. Legal category: POM Marketing authorisation numbers: EU/1/16/1139/001 & 002 Marketing authorisation holder: Intercept Pharma Ltd, 2 Pancras Square, London, N1C 4AG, United Kingdom Package Quantities and Basic NHS cost: OCALIVA 5 mg and 10 mg £2,384.04 per bottle of 30 tablets. Date of revision: 20/DEC/2016 Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/ yellowcard. Adverse events should also be reported to Intercept Pharma Ltd on +44 (0)330 100 3694 or email: drugsafety@interceptpharma.com
Abbreviations. ALP, alkaline phosphatase; FXR, farnesoid X receptor; PBC, primary biliary cholangitis; UDCA, ursodeoxycholic acid. References. 1. OCALIVA (obeticholic acid). Summary of Product Characteristics, 2016; 2. FDA Drug Approval Package: Urso (ursodiol) NDA# 020675. http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20675a.cfm [Last accessed 4 April 2016]; 3. Ding L, et al. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharma Sin B 2015;5:135–44; 4. Nevens F, et al. A Placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 2016;375:631–43.
GASTROENTEROLOGY TODAY - AUTUMN 2017
Presentation: OCALIVA supplied as film-coated tablets containing 5 mg and 10 mg obeticholic acid. Indication: For the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA. Dosage and administration: Oral administration. The starting dose is 5 mg once daily. Based on an assessment of tolerability after 6 months, the dose should be increased to 10 mg once daily to achieve optimal response. No dose adjustment of concomitant UDCA is required in patients receiving obeticholic acid. For cases of severe pruritus, dose management includes dose adjustment such as reduced dosage, temporal interruption or discontinuation for persistent intolerable pruritus; use of bile acid binding agents or antihistamines (see SmPC). No dosage adjustment for elderly. Renal impairment: No dose adjustments are required. Hepatic impairment: No dose adjustment for mild hepatic impairment (Child-Pugh Class A). The recommended starting dosage for moderate/severe (Child-Pugh Class B/C) hepatic impairment is 5 mg once weekly. Titrate to 5 mg and subsequently to 10 mg twice weekly (at least 3 days between doses) if patient does not achieve adequate reductions in alkaline phosphatase and/ or total bilirubin after 3 months, depending on
UK-PP-PB-0120 August 2017
13
NEWS Free information about pancreatic cancer for patients and healthcare professionals Pancreatic Cancer UK has received accreditation from the Information Standard for the fourth year in a row for its range of publications about pancreatic cancer. The resources aim to assist healthcare professionals in giving advice on the disease, and help them provide the best support to patients and their carers. The charity began publishing information resources after hearing from doctors, nurses, specialists and patients that they had struggled to find the right tailored support and information about pancreatic cancer. The resources provide accurate and up-todate information about issues that are of concern to people affected by pancreatic cancer. The assets complement the advice of healthcare professionals, providing a clear and understandable guide to patients and carers. The Newly diagnosed pack is a key resource for people recently diagnosed with pancreatic cancer, containing a range of publications about diagnosis, treatments, diet and information for carers. It can be tailored to the individual patient’s needs and additional information about the specific hospital or local
producing information that is accessible to
both the patient and the carer.
people with additional needs, and will be able to support healthcare professionals in meeting
Pain and pancreatic cancer describes the
the requirements of the Accessible Information
different types of pain pancreatic cancer
Standard.
can cause, provides information on how to describe pain to medical professionals and
The information resources can be downloaded
how pain can be managed and kept under
or ordered for free from the Pancreatic Cancer
control. It also provides information about
UK website: www.pancreaticcancer.org.uk/
painkillers and their side effects, and other
information-and-support/our-publications/
methods that can aid pain relief. Patient Charter: What you should expect from your care explains the standard of care all people with pancreatic cancer should have. Specific pancreatic cancer treatments Information fact sheets are also available for specific pancreatic cancer treatments including; Surgery for operable pancreatic cancer, Stents and bypass surgery, Chemotherapy and Radiotherapy , as well as for a range of Chemotherapy drugs including: Gemcitabine, Capecitabine, FOLFIRINOX, Fluorouracil, Nab-paclitaxel (Abraxane), and Oxaliplatin. We’re here for you: our support services leaflet explains the different ways Pancreatic Cancer UK can support people affected by pancreatic cancer. It includes information about the Pancreatic Cancer UK Support Line, which is run by pancreatic cancer specialist nurses and is available to anyone affected by pancreatic cancer. The free service is available from 10:00am – 4:00pm Monday to Friday by
services can be added.
calling 0800 801 0707 or emailing support@
Pancreatic Cancer: An overview of
Pancreatic Cancer UK Discussion Forum,
diagnosis and treatment will be particularly helpful for people with a recent diagnosis. It broadly covers test results, treatment options, GASTROENTEROLOGY TODAY - AUTUMN 2017
14
outlines how to access a range of support for
pancreaticcancer.org.uk. It also outlines the
Published Monday 3 July 2017 By Ana Sandoiu Source: Medical News Today Researchers have narrowed down a few genetic variants that may cause inflammatory bowel disease. Using genetic “fine-mapping,” researchers have zoomed in on just a few genetic variants that may trigger the autoimmune condition inflammatory bowel disease. Inflammatory bowel disease (IBD) affects between 1 and 1.3 million people in the United States, according to the Centers for Disease Control and Prevention (CDC). The condition can be debilitating, as the body’s own immune system does not recognize parts of its digestive tract and attacks them. It is not currently known what causes IBD,
Support Groups and Living with Pancreatic
nor is there a cure for the condition. But new
Cancer Support Days which are run by the
research brings us closer to understanding this
charity.
disease, as some of the genetic underpinnings for IBD are revealed.
managing symptoms and side effects, as well as the help and support which is available.
Scientists find genes that may cause inflammatory bowel disease
Pancreatic Cancer UK will be publishing resources on fatigue, end of life care and
Researchers from the Wellcome Trust Sanger
Diet and pancreatic cancer is a booklet
information outlining possible requirements
Institute in Hinxton in the United Kingdom
explaining how pancreatic cancer can cause
around diet for pancreatic cancer patients
teamed up with scientists from the Broad
problems with diet, eating and nutrition, as
when being admitted to hospital before the
Institute of MIT and Harvard University, both in
well as how these issues can be managed.
end of the year.
Cambridge, MA, as well as the GIGA Institute of the University of Liège in Belgium, to find
Pancreatic enzyme replacement therapy and how it should be used effectively is explained
The free resources have been reviewed
out which genetic variations are behind the
in detail, and the booklet contains tips to help
by healthcare professionals to ensure all
condition.
patients eat well.
information included is accurate and up to date. Patients and people who have been
The findings were published in the journal
Caring for someone with pancreatic cancer:
affected by pancreatic cancer first hand also
Nature, and the first author of the study is
information for family and carers provides
take part in the review process, to ensure the
Dr. Hailiang Huang, from the Massachusetts
information about how carers can support their
content is relevant and easy to understand.
General Hospital and the Broad Institute of
loved one, as well as for themselves. It also
Pancreatic Cancer UK is also working to
MIT.
NEWS Studying the genetic variants behind IBD
In the new research, Dr. Huang and team used “high-density genotyping” and applied three
Dr. Huang and colleagues performed a
statistical analyses. As a result, they found 94
genome-wide association study (GWAS) of
genetic locations.
67,852 people. A GWAS is a method that quickly scans for biomarkers across whole
Of these, the team identified a further 18
sets of DNA, or genomes, of a large number
locations that they could associate with
of people in order to find genetic associations with a particular disease. As the authors of the new study report, previous studies have found 200 genetic loci associated with the illness, but it was not entirely clear precisely which variants were involved in the disease. Dr. Huang explains further, saying, “An issue with studying complex diseases is that it can be hard to move from genetic associations,
a single genetic variant, with a degree of certainty of over 95 percent. Additionally, they found 27 associations to a single genetic variant with over 50 percent accuracy. ‘Zooming in on the genetic culprits’ This procedure of “fine-mapping” allowed the researchers to see which genes are involved in
“We have taken the biggest ever data set for IBD and applied careful statistics to narrow down to the individual genetic variants involved. Now we have a clearer picture of which genes do and do not play a role in the disease. We are zooming in on the genetic culprits of IBD.” Co-lead author Dr. Jeffrey Barrett, Wellcome Trust Sanger Institute
the condition and which are not, by separating
Co-lead author Prof. Michel Georges, from
similar evidence, to knowing exactly which
these genetic variants from others that were
the GIGA Institute of the University of Liège,
variants are involved.”
closely located in the genome.
also weighs in, saying, “These results will help
“We need to be careful in deciding when we are
Furthermore, the authors note that the fine-
human diseases like IBD, and possibly for
sure we have the right variant. This new technique
mapping of large population samples can
the development of personalized medicine
helps us to pinpoint which genetic variants are
turn genetic associations into “statistically
by finding biomarkers for more effective
implicated in IBD with greater confidence.”
convincing causal variants.”
prescription of existing drugs.”
usually including many genetic variants of
towards rational drug discovery for complex
GASTROENTEROLOGY TODAY - AUTUMN 2017
15
NEWS in a significant proportion of these patients. Currently, the available drugs need constant
Balancing the scales: GI research and clinical commitment
monitoring and can be life limiting. “Anti-TNF drugs work by interrupting the inflammation via the TNF pathway. These drugs (infliximab, adalimumab and
Source: The National Institute for health
golimumab) work well but not for everyone. We
Reserach (NIHR)
are now looking at different therapies and new drugs, such as those that target white blood
At Hampshire Hospitals Foundation Trust
cell migration and novel pro-inflammatory
(HHFT) in Basingstoke, Dr Matthew Brown has
pathways to treating these diseases. The
gained significant early success in research in
anti-TNF drugs are delivered either by sub
gastrointestinal medicine and his sub-specialty
cutaneous injections or intravenous infusions
of inflammatory bowel disease, despite his relatively recent appointment as a consultant in 2013. “I finished my registrar training in 2013 and started looking for a clinical based job. I had been in Nottingham completing a NIHR funded PhD (laboratory – based) but was more interested in direct patient contact.”
“In inflammatory bowel disease, such as Crohn’s disease and ulcerative colitis, I see lots
but there are some limitations to intravenous delivery, so research is now returning to orally delivered drugs.
of young patients, many of whom go through biological antibody treatments, which are
“When looking at clinical trials we have to be
associated with potentially serious side effects.
selective and identify trials that will work for
It is important that we identify other therapeutic
and are suited to our patient population. It is
options for these chronic, incurable diseases
always good to be involved in big multicentre trials, both on the portfolio and from
“There are two peaks in these conditions: at
commercial companies. I am working with
recruiting to research studies. I am quite
their onset in a person’s teens or 20s (more
drugs that look as if they might work and will
passionate about being in at the beginning of
severe course); then again in their 50s or
really benefit a large number of patients. I work
the roll out of new treatments at the bedside
60s. More often than not, these young people
with HHFT’s R&D team. They are proactive
and want to be instrumental in opening up
with Crohn’s disease will need surgery but, in
in getting significant levels of research off the
studies to patients where they can really
the next 10 or 20 years, research will tell us
benefit from access to drugs that could make
whether, if we start drug intervention earlier,
a big difference.
we will be able to avoid surgical intervention
“As soon as I could, I got involved with
ground; it comes down to who’s interested in taking it on. We have more than 12 GI studies on-going. “At HHFT we have started to see the benefits of previous trials, some of which we have participated in, as new drugs become available to all patients. By participating in phase 3 clinical trials we are able to offer our patients access to novel drugs which work on potentially new therapeutic pathways in IBD. Also, phase 4 study participation provides our patients with access to new drugs with proven efficacy in IBD but yet to be licenced or approved for UK use.
GASTROENTEROLOGY TODAY - AUTUMN 2017
Our successful recruitment to studies like these has benefited our patients and contributed to “real world” data on the therapeutic success of these newer agents outside the clinical trial environment. The strength of the research team is key to success in clinical research. The GI team comprises two gastroenterology trained research nurses; Barbara King and Caroline Palmer. They are supported by a part time clinical trials assistant. The research nurses work closely with many departments such as endoscopy, outpatients, the GI ward and the pharmacy. Regular meetings are held to determine future trials, how the recruitment of current trials is progressing and any other issues.
16
NEWS “The research nurses also see patients, ensure they have the necessary documentation and ensure samples are taken on time; the nurses are the key to success because they do the majority of the legwork. It couldn’t be done without them. “Some studies are low maintenance; drug studies are more commitment. ENDCaP-C is a non-drug study, which screens for dysplasia in ulcerative colitis but involves samples taken at scheduled colonoscopic surveillance. Patients are recalled if they are deemed at higher risk of colon cancer. It is a study with minimal patient participation (at most, their next colonoscopy would be brought forward), and high input from the research team, especially nurses and CTAs. There is added benefit that recalling patients is in their best interest. It is an example of a predominantly basic science study which offers the benefit of expanding our scientific knowledge and aiming to identify participants with IBD who may be at high risk of colorectal cancer. By identifying these individuals, more frequently, thorough surveillance can be undertaken to hopefully identify pre-malignant lesions at an early stage. “My focus is to be able to give my patients options that would not normally be available. The job satisfaction comes from giving the patients a better deal. There’s not exactly a lot of glory… There is a different pressure as an academic researcher; you’re only as good as your last article or when you were last published and in which journal. Academic medicine entails huge pressure because there’s a team under you that also relies on you.”
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“10 years ago, district general hospitals conducting research was a novelty. Now the opportunity is available but the challenge is made a big difference and, through CRN Wessex, some of the barriers to undertaking research have been removed and access is smoother. To make sure you have the available
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time in the day job, you need the research role written into your job plan because it’s vital you achieve balance with your everyday role. I’ve just been fitting it in, but it’s been hard. After all, this is a service job… In time you can negotiate more flexibility. Following a recent assessment of my job plan, I now have a little more space to focus on research, and am looking at taking on more phase 3 randomised
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GASTROENTEROLOGY TODAY - AUTUMN 2017
finding the time. The advent of the NIHR has
We work to locally agreed integrated pathways helping CCGs provide patient centred care delivered by high volume endoscopy staff with a single point of access
studies.”
17
NEWS their digestive condition is not understood or taken seriously enough. We will raise the
Core
banner for all digestive disorders to remove stigma and start talking, free from fear, shame
In 1971, a trust fund called the Digestive
and embarrassment.
Disorders Foundation was established with the first donation of £500 from the British Society of Gastroenterologists, and trustees Sir Francis Avery Jones, Dr Nelson Coghill and Dr Thomas C Hunt, one time physician to Winston Churchill. All three were past-Presidents of the BSG
Digestive disorders affect huge numbers of significant birthday. We have based this on the market research from stakeholders and patients and on values that came out loud and clear that will inform our vision and strategy
and pioneers for the recognition and
going forward – honest, brave and bold.
development of gastroenterology. This was
This applies as much to patients as it does to
just two years after Gastroenterology had
you, the health care professionals that care for
been recognised by The Royal College of
them. If the gut works, life works.
Physicians as a specialty within General Medicine. Since 2004, the foundation has
The proposed name of the charity alone has
been known as Core.
had visceral reaction: Guts UK!
The development of the charity in the first
As Sir Francis Avery Jones said, in 1981:
decade was due largely to the personal effort
NHS time, from GPs through to specialist consultants. Uniquely placed within the British Society of Gastroenterology, we are the only charity in the UK leading the fight against all conditions of the gut, liver and pancreas, from top to tail. We are committed to upholding the original mission of funding vital research, providing expert information and promoting awareness around digestive health. We would love to have your support, feedback and involvement to make this charity your
of Dr Hunt, “a man of stature, authority, and
“….digestive diseases have remarkably little
curiosity” and the diplomat of British and world
emotional appeal…(there is) diffusion of
gastroenterology. In 1980, just before his
support among the many subdivisions of the
untimely death, he addressed the AGM of the
have benefitted today from research someone
(digestive system); the gastrointestinal tract,
Foundation, ending his report by saying, “If, as
else paid into years ago. Encourage folks
liver, gall bladder and pancreas. Unfortunately
we hope, the Foundation expands….we must
now to pay it forward for the next generation,
digestive is an insipid meaningless title….
try to make sure of a continuing and growing
so that no-one else goes through the same
journalists laugh out loud at our title…is it
misery, discomfort or pain.
income. To obtain this will almost certainly mean more publicity, with bigger accommodation, more secretarial help, and more aid from willing laymen….to grow and rival the large foundations such as those which sponsor research into cancer and heart disease…” At Core,we believe it’s time for guts to have their day. The digestive health of our nation is in our hands and has never been more in the nation’s consciousness. Research into our guts is woefully underfunded and has been for decades. It’s time to have the guts to make our pioneering work rival levels of investment into GASTROENTEROLOGY TODAY - AUTUMN 2017
18
people, every day - an estimated 12 % of all
heart and cancer research.
charity of choice: the one you recommend to your grateful patients and their families. They
related to biscuits? Embryologically, the one accurate term is GUT. Could we have The
At 50 years old, we aim to make Dr Hunt, and
British Gut Foundation?”
all those charity founders and supporters over the decades, as proud as punch that research
We think he would approve of our suggested
into gastroenterology finally gets its day in the
new brand.
limelight. No more waiting, the time is now.
With our new name and improved outreach,
Julie Harrington, CEO (with thanks to J E
Guts UK will be the voice for those who feel
Lennard-Jones’ brilliant historical notes)
First endoscopic stricturotomy with needle knife study for intestinal strictures in IBD
So, the team at Core makes no apologies for their ambitious plans to transform the
Published Wednesday 3 May 2017
landscape of research into gastroenterology.
Adapted Media Release
We aim to be a very different charity by the
Source: Medical News Today
time we celebrate our 50th birthday in just under 4 years’ time. We must turn the charity
Cleveland Clinic doctors have published
from one set up by doctors to answer doctors’
the first study illustrating the safety and
questions to one that really shows a deeper
efficacy of endoscopic needle knife therapy
understanding of the needs and challenges
for intestinal strictures in patients with
faced by those we seek to help.
inflammatory bowel disorder (IBD).
These last few weeks, we have started to
“We pioneered this procedure,” said Bo Shen,
test a revitalised brand identity that we hope
MD, Medical Director of Cleveland Clinic’s
takes us above the parapet and on to our next
IBD Center. “And our research shows that it
NEWS is effective and can have advantages over
strictures in the upper GI tract when he decided
“These normally active immune cells are less
other conventionally used treatments, such as
it might be a good alternative therapy for IBD
responsive to stimulation, secreting fewer
medical therapy, balloon dilation and surgery.”
patients with strictures in the lower GI track.
mediators and dividing less. This type of response is often observed in chronic infections.
Shen’s study, which was co-authored with
He says the technology allows physicians
research fellow Nan Lan, MD, was featured as
to be much more precise when opening up
“This is an important discovery, particularly as it
the cover story in the April 2017 issue of the
strictures. “You have more control over how
helps to further distinguish between the different
journal Inflammatory Bowel Diseases. Dr. Lan
deep you cut and where you cut,” he said.
types of irritable bowel syndrome. This may
presented their findings in May at Digestive
“This is a major advantage.”
eventually help us to better understand how to diagnose and treat the disease,” he says.
Disease Week 2017. In their study, Drs. Shen and Lan reviewed the records of 85 patients with strictures treated
Exhausted immune cells linked to irritable bowel syndrome
Dr Hughes says there is much research into IBS to show its links with stress, and it is known that cortisol and stress hormones can
by needle knife stricturotomy (NKSt) between 2008 and 2016 at Cleveland Clinic’s Center for
Published Wednesday 21 June 2017
inhibit the immune system. But until now, such
Inflammatory Bowel Disease.
Adapted Media Release
T-cell exhaustion had not been described in
Source: Medical News Today
IBS-D patients.
there were a total of 231 NKSts performed on
Adelaide researchers have for the first
“Irritable bowel syndrome takes a real toll
the 85 subjects. Passage of the scope through
time discovered that a specific type of
on patients,” Dr Hughes says. “It can affect
each stricture was achieved in 100 percent of
irritable bowel syndrome is associated with
people in the prime of their lives, it’s a chronic
the patients.
exhaustion of the immune system in patients.
disease that can last a long time, and the
Developing nonsurgical treatments for IBD
The discovery has been made by a team
patients such as NKSt results in better quality
led by Dr Patrick Hughes, Senior Lecturer
“Anything we can do to better understand the
of life, according to Dr. Shen. “Multiple bowel
with the Adelaide Medical School, University
disease and to help reduce its debilitating
resection surgeries can shorten patients’
of Adelaide, and a member of the Nutrition
effects on patients will be welcome,” he says.
intestinal tracts while noninvasive procedures
& Metabolism theme, South Australian
preserve them.”
Health and Medical Research Institute
This research has been supported by the National
(SAHMRI).
Health and Medical Research Council (NHMRC).
inflammation and scarring, are a common side
Now published in the international journal
Article: Longitudinal analysis indicates
effect of IBD. Patients with Crohn’s disease or, to
Gut, the research focused on a small
symptom severity influences immune profile in
a lesser degree, ulcerative colitis after surgery,
sample of patients with various types of
irritable bowel syndrome, Chris Mavrangelos,
often develop them as their conditions progress.
irritable bowel disease, and, for the first
Melissa A Campaniello, Jane M Andrews,
Strictures also may occur after a bowel resection.
time, followed them for a year comparing
Peter A Bampton, Patrick A Hughes, Gut, doi:
They can cause abdominal pain, diarrhea,
blood samples when patients experienced
10.1136/gutjnl-2017-314308, published online
nausea, vomiting, weight loss and malnutrition.
symptoms to when they were symptom free.
10 June 2017.
To treat strictures, physicians typically have
All patients
turned to surgery or a procedure called
with diarrhoea-
endoscopic balloon dilation (EBD) that
predominant irritable
stretches out the constricted area, however,
bowel syndrome
this therapy carries a risk of perforation and
(IBS-D) were found
intestinal bleeding, and usually the therapeutic
to have the same
effect typically lasts only three to six months
kind of exhaustion in
before the stricture returns.
their T-cells.
The interval between endoscopic and
“For the first time,
surgical interventions and the interval from
we’ve discovered
the treatment to the return of the stricture was
that in patients
longer, Drs. Shen and Lan found, if patients
with irritable bowel
first had NKSt. “For example, if you need EBD
syndrome associated
every three months, you need it every six
with diarrhoea, their
months after NKSt,” said Dr. Shen.
T-cells seem to be
Because many patients had multiple strictures,
treatments currently available are poor.
Strictures, the narrowing of the intestines due to
down,” Dr Hughes
endoscopic needle-knife technology to treat
says.
GASTROENTEROLOGY TODAY - AUTUMN 2017
‘out of puff’ or run Dr. Shen was already experienced in using
19
POSTERS
THE BRITISH SOCIETY OF GA PRIMARY BILIARY CHOLANGITIS TREAT
“
Hirschfield GM, Dyson JK, Alexander GJ, Chapman M, Collier J, Hubscher S, Patanwa
The goals of therapy in PBC are prompt diagnosis, e prevention of end-stage complications of liver disease
DIAGNOSIS
RECOMMENDATION 1: We recommend that any patient with persistently elevated cholestatic liver biochemistry (raised ALP or GGT) without an alternative cause, should have autoantibodies checked by immunofluorescence for anti-mitochondrial (AMA) and anti-nuclear (ANA) reactivity. (Strong; High) RECOMMENDATION 2: We recommend that the presence of AMA (greater than 1 in 40) or PBC-specific ANA in the context of cholestatic liver biochemistry is sufficient for reaching the diagnosis of PBC in the absence of alternate liver disease. (Strong; High) RECOMMENDATION 3: We recommend that for patients in whom the clinical suspicion for PBC is high, but classical indicators of disease are discordant (e.g. normal liver biochemistry, serology at a low titre) further investigation and review is required prior to establishing a diagnosis of PBC or initiating therapy. (Strong; Moderate) RECOMMENDATION 7: We recommend in the absence of diagnostic autoantibodies, the confirmation of PBC requires a liver biopsy. (Strong; Moderate)
TREAT & RISK STRATIFY RECOMMENDATION 11: We recommend all patients with PBC should be offered structured lifelong follow-up, recognising that different patients have different disease courses, and may require different intensity of follow up. (Strong; Medium). RECOMMENDATION 13: To identify those at greatest risk of disease progression, we recommend that all patients have individualised risk stratification using biochemical response indices following one year of UDCA therapy. (Strong; High) RECOMMENDATION 18: We recommend that oral ursodeoxycholic acid at 13-15mg/kg/day is used as the first-line pharmaco-therapy in all patients with PBC. If tolerated treatment should usually be lifelong. (Strong; High) RECOMMENDATION 19: In patients with inadequate response to UDCA (or UDCA intolerance) as defined by ALP >1.67x ULN and/or elevated Bilirubin <2x ULN, the addition of OCA (initial dose 5mg per day, titrating to 10mg per day at 6 months if tolerated) has been associated with improvements in biochemical surrogates of disease activity reasonably likely to predict improved outcomes. We recommend, in keeping with the NICE evaluation of OCA, that the addition of OCA for patients with an inadequate response to UDCA, or intolerant of UDCA, is considered. (Strong, Low)
GASTROENTEROLOGY TODAY - AUTUMN 2017
20
PATIENTS BENEFITING FROM SPECIALIST MDT • Disease un- or under-responsive to UDCA • Age at diagnosis – young patients with PBC are at higher risk of progressive disease • Approaching need for consideration of liver transplantation • Patients who may require transplant who need complex non-liver surgery • HCC complicating PBC • Overlap syndromes • Intractable symptoms unresponsive to conventional therapy • Complex therapeutic questions e.g. where other drugs with potential impact are being considered for intercurrent disease (e.g. biologicals for rheumatological disease)
OVER
PBC is an autoimmune liver disease in which a cycle of immune media culminate over time in an end-stage biliary cirrhosis. Both genetic and
PBC is most prevalent in women and those over the age of 50, but a s younger age at onset (<45) and advanced disease at presentation a diagnosed through the combination of cholestatic serum liver tests an are not cirrhotic, and the term cholangitis is more reflective of their symptoms that can be burdensome for patients, and management of progression and symptom burden. Licenced therapies include Ur experimental new and
Disease management focuses on initiation of UDCA for all patients, including in particular the response to treatment. Those intolerant of UDCA treatment failure (frequently reflected in trial and clinical pra considered for second-line therapy, of which OCA is the only additional life-long and must address not just treatment of d
POSTERS
ASTROENTEROLOGY/UK-PBC TMENT AND MANAGEMENT GUIDELINES
ala I, Pereira S, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G and Jones DE
early treatment, appropriate risk stratification and the e, alongside the management of associated symptoms
RECOMMENDATION 4: We recommend all patients with suspected PBC should have a baseline abdominal ultrasound as part of their assessment. (Strong; High) RECOMMENDATION 12: Risk assessment should evaluate disease severity and activity at baseline and on treatment. We recommend a combination of serum liver tests (to identify those with an elevated bilirubin, a platelet count <150, or biochemical disease activity on treatment), imaging (liver ultrasound to identify overt cirrhosis and splenomegaly; transient elastography to identify increased liver stiffness) and recognition of young age at disease onset (<45 years). These can all aid risk stratification for patients with PBC. (Strong; Moderate) RECOMMENDATION 25: We recommend that in all patients with a bilirubin >50µmol/L (including those treated with UDCA) or evidence of decompensated liver disease, consideration should be made regarding suitability for liver transplantation, through discussion with a Hepatologist linked to a liver transplant programme. (Strong; High) RECOMMENDATION 26: We recommend that in patients where cirrhosis is suspected, HCC surveillance should be carried out according to NICE guidelines. (Strong; Medium) RECOMMENDATION 27: We recommend that patients with suspected portal hypertension should be screened for gastro-oesophageal varices according to BSG guidelines. (Strong; Medium) RECOMMENDATION 28: We recommend that ascites and hepatic encephalopathy should be treated as in standard practice. (Strong; Medium)
ACTIVELY MANAGE RECOMMENDATION 20: We recommend all patients should be evaluated for the presence of symptoms, particularly fatigue and itch. Clinicians should recognise that severity of symptoms does not correlate with stage of disease. (Strong; medium) RECOMMENDATION 24: We suggest that patients with symptoms resistant to medical therapy should be referred for specialist management regardless of disease severity. (Weak; medium) RECOMMENDATION 39: We recommend that patients with PBC should be offered the chance to seek support from patient support groups. (Strong, Moderate)
PATIENT RESOURCES
ated biliary epithelial cell injury, cholestasis and progressive fibrosis can d environmental influences are presumed relevant to disease initiation.
A number of on-line resources are available for patients. Recommended websites include:
spectrum of disease is recognised in adult patients globally; male sex, are baseline predictors of poorer outcome. As disease is increasingly nd presence of anti-mitochondrial antibodies, most presenting patients r presenting disease. Disease course is frequently accompanied by f patients with PBC must address, in a life-long manner, both disease rsodeoxycholic acid (UDCA) and Obeticholic acid (OCA), alongside d re-purposed agents.
• www.uk-pbc.com (UK-PBC)
, and risk stratification based on baseline and on-treatment factors, treatment with UDCA, or those with high risk disease as evidenced by actice as an ALP >1.67 x ULN and/or elevated bilirubin) should be l currently licenced NICE recommended agent. Follow up of patients is disease but management of associated symptoms.
• www.britishlivertrust.org.uk (The British Liver Trust) • www.pbcfoundation.org.uk (The PBC Foundation) • www.livernorth.org.uk/index.htm (LIVErNorth) • www.liver4life.org.uk (Liver4Life) • www.patient.co.uk/health/primary-biliary-cirrhosis-leaflet (NHS information)
UK-PBC is a MRC Stratified Medicine Platform Final peer review of recommendations is pending
GASTROENTEROLOGY TODAY - AUTUMN 2017
RVIEW
”
STAGE & SURVEY
21
POSTERS
Survival rates have improved for almost every disease of every organ in the last few decades, with one notable exception: liver disease1 (Lancet, 2014) INTRODUCTION • Patients with acute decompensated chronic liver disease (AD-CLD) are notoriously difficult to manage • The underlying pathophysiology is complex, whilst common medical problems, such as sepsis and renal failure, can present atypically • The burden of CLD, and its mortality, is ever-increasing due to alcohol consumption, obesity and viral hepatitis1 • The 2013 NCEPOD* report “Measuring the Units” showed that the treatment of patients admitted with AD-CLD is suboptimal, partly due to incomplete and inappropriate initial management by non-specialists2 • The BSG* and BASL* therefore created the “Decompensated Cirrhosis Care Bundle – First 24 Hours”, a ‘gold standard’ acute management checklist to help the non-specialist before subsequent gastroenterologist review • We wanted to see if use of this bundle, combined with education for junior doctors about liver disease, could improve early patient management and overall outcomes at Tunbridge Wells Hospital (TWH)
METHODS
n = 30
n = 33 March 2015
March 2015
September 2015
No specific guidance encouraged locally for management of patients with AD-CLD, though ‘liver bundle’ available on internet Patients identified with help from Clinical Coding Dept. Data gathered from hospital notes, electronic Pathology and iSoft Patient Centre systems
• ‘Liver bundle’ introduced – reminder posters in A+E and MAU • Formal FY1 teaching re: management of AD-CLD by TWH gastro. registrar (AS) • Ad hoc teaching on the wards re: liver disease and ascitic taps by AS
Patients identified from acute medical take list, ward Data collection (on Microsoft Excel®): referrals and gastro. ward inpatients length of admission and no. of readmissions completion of bundle components – i.e. ‘gold standard’: FBC, U+Es, LFTs, coagulation, glucose, CRP, bone profile, blood cultures, MSU*, CXR*, US abdomen*, ascitic tap, empirical antibiotics for SBP*
RESULTS
GASTROENTEROLOGY TODAY - AUTUMN 2017
22
Bundle completion 35
30
Number of patients
• Pre-intervention, no bundles were filed in the notes. Post-intervention, it was completed 28/30 times (93%) in total, and 14/30 (47%) in < 6 hours (BSG guidance) • The completion of all investigations and interventions increased or remained at 100%, e.g. ascitic tap – 71% to 91% • Mean length of stay increased from 6.4 days to 9.0 days, with no effect on mortality • However, there was a marked reduction in the number of readmissions
Not completed
25
At any point during admission
20
15
Within 24hrs
10
On admission 5
0
Pre-intervention Post-intervention
^1 x profound thrombocytopaenia
CONCLUSIONS • • • • •
Our interventions led to improvements both in the initial management of patients and overall outcomes Despite increased mean length of stay, there was a marked decrease in the readmission rate This suggests that there was better optimisation of their clinical condition, obviating the need for readmission This has a clear benefit for patient care AND a large financial saving, given that readmissions are funded by the Trust, not the CCG* Further work will focus on education of new FY1s and re-audit in the autumn
*NCEPOD: National Confidential Enquiry in to Patient Outcomes and Deaths; BSG: British Society of Gastroenterology; BASL: British Association for Study of the Liver; MSU: midstream urine; CXR: chest x-ray; US: ultrasound; SBP: spontaneous bacterial peritonitis; CCG: clinical commissioning group References:
1. Williams R, Aspinall R, Bellis M, et al. Addressing liver disease in the UK: a blueprint for attaining excellence in healthcare for liver disease and reducing premature mortality from the major lifestyle issue of excess alcohol consumption, obesity, and viral hepatitis. Lancet 2014; 2. http://www.ncepod.org.uk/2013report1/downloads/MeasuringTheUnits_FullReport.pdf
COMPANY NEWS
NICE DG30 DECLARES FAECAL IMMUNOCHEMICAL TESTING FIT FOR PURPOSE by Matthew Davis, Senior Product Manager, Alpha Laboratories Ltd., Eastleigh, UK, www.alphalabs.co.uk The long awaited NICE Guidance DG30 on “Quantitative faecal immunochemical tests (FIT) to guide referral for colorectal cancer in primary care” was published in July 2017. Release of this document has now helped to address the debate raised by the NG12 cancer referral guidelines published in June 2015. This recommended Faecal Occult Blood Tests (FOBT) as an aid to the 2 week wait referral pathway for patients with suspected colorectal cancer from primary care, and where a definitive diagnosis was unclear. Controversy with the NG12 guidelines arose due to the use of the terminology of FOBT, since this method had been withdrawn from the patient pathway in the 2005 guidelines. Although a generic terminology, the majority of FOBT technology at that time was primarily guaiac based which was considered to have poor specificity and sensitivity for use in identification of colorectal cancers in symptomatic patients.
cancer. However, they acknowledge that using a lower cutoff than 10 µg Hb/g faeces would create disparity between the available methods, and hence have asked that manufacturers of
The new guidance (DG30) focuses on the peer reviewed data for the more sensitive and specific Faecal Immunochemical Test (FIT) technology that is now available. Using the available data, the Diagnostics Advisory Committee has created an economic model for each of the FIT methods under review.
these technologies should provide performance characteristics to prospective laboratories. The guidance also recognises that FIT detects a symptom of colorectal cancer (haemoglobin) that could also be associated with a range of other conditions. Data from studies reporting
The recommendations from the review, are that quantitative FIT should be used in primary care to guide referral for suspected colorectal cancer in people without rectal bleeding, who have unexplained symptoms, but who do not meet the criteria for a suspected cancer pathway referral outlined in the NICE NG12 guideline (see table below)
diagnostic accuracy for multiple target conditions in the same population, suggested that up to 28.9% of people with a falsepositive FIT result for colorectal cancer, did have some form of serious bowel pathology, such as inflammatory bowel disease or high-risk adenoma. The guidance concludes that it is plausible that the number of false-positive results that occur when using the tests to rule out colorectal cancer, could be partially offset by detecting
2005 NICE Guide line
2WW if +ve FOB
No recommendation
2WW if +ve FOB
No recommendation
2WW if +ve FOB
No recommendation
Aged under 60 years with iron deficiency anaemia
2WW if +ve FOB
2WW for unexplained Fe deficiency anaemia using M/F specific Ref cut off
Aged 60 years and over with anaemia even in absence of iron deficiency
2WW if +ve FOB
Patient group Aged 50 years and over with unexplained abdominal pain Aged 50 years and over with unexplained weight loss Aged under 60 years with changes in bowel habit
2WW for cases of iron deficiency anaemia only (as above)
other treatable bowel pathology. Finally the guidance suggests that commissioning groups that implement the use of FIT in their patient referral pathway should be auditing their outcomes to include: • The number of patients referred under the 2 week wait for suspected cancer pathway • The number of patients diagnosed with colorectal cancer • The resultant number of colonoscopies and CT colonographies requested Additionally there is also the request for further research into whether faecal haemoglobin levels are influenced by age, gender
Furthermore NICE concludes that a cut-off of 10 µg Hb/g faeces should be used to define the threshold for ruling out colorectal
and medicines that increase the risk of gastrointestinal bleeding, and whether a risk score could be used to refine the use of FIT in
GASTROENTEROLOGY TODAY - AUTUMN 2017
June 2015 NICE NG12
primary care.
23
COMPANY NEWS
Who Needs That Valuable Clinic Space? BÜHLMANN IBDoc® Calprotectin helps you to better manage clinic resources and improve patient care. IBD patients can perform their own tests at home and read them using Smartphone technology: ■ Rapid quantitative
However, whilst DG30 addresses the clinical advantages and need for implementing FIT, it does not deal with the practicalities of how commissioning groups may implement it. The core benefit of FIT is the ability to detect low levels of faecal haemoglobin (f-Hb). The test is very specific for the intact Hb molecule, (unlike the original Guaiac test, which detected the haem moiety). Originally requests for FOBT required a stool sample to be provided by the patient in the blue topped tubes, with the faeces being processed by laboratory staff to generate the result. However, haemoglobin is an unstable molecule, more so in faeces, an environment where digestive enzymes and variable gut flora can accelerate molecular destruction. Additionally the transport time can be variable and the sample can be subject to differing ambient temperatures providing further uncertainty over the rate of f-Hb degradation. The new FIT technologies have specific collection devices which overcome such sample integrity challenges, by buffering and stabilising any haemoglobin present in the fresh stool sample. In particular, the HM-JACKarc (Alpha Laboratories, UK) device can protect the f-Hb for up to 120 days, if the sample can be refrigerated or 14 days at ambient temperature. However, this benefit is only possible from fresh faeces. Thus the ideal solution is to get the patient to collect their sample directly into the specific collection device, to retain as much of the f-Hb from the fresh sample.
calprotectin results for patient and clinic ■ Helps prioritise clinic space ■ Helps monitor mucosal health and predict flares ■ Connect remotely with patients ■ Patient involvement and reassurance
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Having concluded that the best sample is obtained by getting the patient to collect it directly into the sample device, the next challenge is to provide the best logistics for both the delivery and return of the sample device. This is especially important for patients in rural areas with transportation limitations.
GASTROENTEROLOGY TODAY - AUTUMN 2017
Some sites in Scotland have been running FIT in primary care for over a year now and due to the geography of the areas covered, different laboratories use various methods for distribution and return of the sample. One site uses postal services for delivery to the patient and return of the collection device to the lab. Another produces a patient pack which is provided in the GP practice. The patient then returns to the practice with the sample which is collected for onward transportation to the laboratory. For those looking to implement FIT as a new test service, it is important therefore to communicate effectively with all stakeholders, so that considerations can be made on sample pathway and its ultimate impact on the patient referral process. To find out more about faecal immunochemical testing in the patient pathway, including case studies from hospitals already implementing the service, visit www.alphalabs.co.uk/focusonfit or contact marketing@alphalabs.co.uk
Tel: +44 (0)23 8048 3000 | Web: www.calprotectin.co.uk
24Gastro-Today_Half-Ad_Feb17.indd 1
17/01/2017 10:15:57
COMPANY NEWS
THE RELATIONSHIP BETWEEN IBS AND BACTERIA Intro Irritable Bowel Syndrome (IBS) is the most common functional bowel disorder, with a prevalence of 1025%[1] and accounts for up to 50% of visits to general practitioners for GI complaints[2]. The phenotype is markedly heterogeneous and it may
Evidence of bacterial disturbance causing an IBS phenotype: Lines of evidence: • Post-Infectious-IBS (PI-IBS) • Antibiotic associated IBS symptoms • Small intestinal bacterial overgrowth (SIBO)
be associated with altered bowel
Post-infectious IBS (PI-IBS), which bears close resemblance to IBS-D, is a
habits, bloating, and/or distension;
surprisingly common result of acute gastroenteritis (primarily of bacterial
however recurrent lower abdominal
aetiology) with a reported incidence of between 5-32%[4]. The suggested
pain differentiates it from functional
pathophysiologic mechanisms here include increased intestinal
constipation and diarrhoea. Diagnosis is widely acknowledged to rely
permeability, altered motility, and persistent intestinal inflammation[4].
upon the absence of any specific or unique organic pathology, such as
Research published in 2015 showed that host antibodies to a toxin,
IBD or coeliac disease, however, developments in microbiota research
cyto-lethal distending toxin B (CdtB), produced by Campylobacter jejuni
are beginning to challenge this assertion.
cross-react with vinculin (a host epithelial cell adhesion protein); the presence of which predicted progression to an IBS-like phenotype[5]. The
The microbiota in health and disease: The healthy adult GI tract is home to a staggering diversity (>1000 species per individual) and number of bacterial
animals in this experiment had changes in stool form, increased rectal intra-epithelial lymphocytes (also seen in humans with IBS), and levels of anti-CdtB correlated with the levels of small intestinal bacterial overgrowth (SIBO). Intriguingly anti-CdtB titres were significantly higher in D-IBS subjects compared to non-IBS subjects (P<0.001), therefore potentiating its usefulness as a future biomarker in the workup of chronic diarrhoea.
species (>10 times our own human cells)[3]. Intensive research in this field over the last decade suggests that the
SIBO
bugs we host have a profound impact on numerous physiological processes both within the GI tract and beyond.
Small intestinal bacterial overgrowth (SIBO), defined by an excessive
The disruption in bacterial diversity and composition, commonly referred to
amount of bacteria in the small intestine, may be a cause of irritable bowel
as dysbiosis, found in otherwise disparate conditions ranging from IBS and
syndrome. Determining SIBO prevalence from IBS studies is hindered
IBD, to autism and ADHD, has been one of the most intriguing discoveries
by conflicting results, and the validity of current routine diagnostic tests
of recent decades, and provides an exciting opportunity to improve human
(culture and glucose and lactulose-hydrogen breath tests) have been
health through bacterial augmentation.
criticised for their lack of both sensitivity and specificity [6]. The reduction its modest clinical benefit in diarrhoea-predominant IBS patients, however
Are the bacteria in IBS patients different from controls?
SIBO was not tested in these patients and the underlying mechanism of action remains to be clearly defined. Determining the role small bowel bacteria play in IBS pathophysiology will require large-scale studies that apply culture-independent molecular testing that are capable of a more
Efforts to define a single ‘healthy’ microbiota have failed, owed to the
detailed exploration of host-gut microbial cross-talk.
myriad forces under which bacteria live in the human gut. Diet, genetics, living environment and even gender play a hand in shaping the community of microorganisms that residing within us. With that said the majority of IBS subjects have a demonstrable alteration in their intestinal microbiota compared to healthy controls. Studies have identified both a general decrease in diversity and more specifically a decrease in Bifidobacterium and Lactobacilli spp. abundance[1]. Whether these observed differences are the cause or result of IBS, and what on-going implications they may have, remains to be elucidated.
“Patients prescribed antibiotics for non-GI complaints were more than three times as likely to report chronic bowel symptoms”
GASTROENTEROLOGY TODAY - AUTUMN 2017
in microbial richness shown with rifaximin therapy may be responsible for
25
COMPANY NEWS Antibiotics and IBS (iatrogenic IBS) Antibiotics significantly alter gut microbial ecology, namely a collapse in diversity, and disrupt interactions with host metabolism [7]. A consequence of this is the frequent disturbance in bowel habit, particularly with broad-spectrum antibiotics (5-62%)[8], and numerous animal and human studies provide evidence of the role antibiotics play in IBS pathogenesis. Early life exposure to antibiotic alters microbial composition and leads to enduring effects on visceral pain in rodents [9]. Evidence that this also occurs in adulthood was shown in a prospective study in which consecutive patients prescribed antibiotics
mice, a significant delay in gastrointestinal motility is observed [17]. It is perhaps not surprising that patients with IBS-D have been found to have an increased expression of TLR4 from colonic biopsies [18]. It is interesting to note that whilst low dose LPS is essential to maintain neuronal survival, higher doses results in neuronal toxicity [17] and this may hypothetically be a result of dysbiosis (disruption of the microbiota). Augmentation of the microbiota, with probiotics, could potentially suppress gram negative bacteria, thereby reducing LPS concentration and ameliorating IBS symptoms. In support of this, Lactobacillus paracasei has been shown to attenuate gut muscle hypercontractility in an animal model of post-infectious IBS [19].
for non-GI complaints were more than three times as likely to report chronic bowel symptoms as controls [10]. Moreover, a large GP survey of over 400 patients, aged 18-80 years, found antibiotic usage
Probiotic evidence in the management of IBS
was strongly associated with IBS symptoms (OR 3.70). Interestingly probiotics, in rodent studies at least, can ameliorate visceral pain
The WHO define probiotics as ‘live microorganisms, which when taken
induced by antibiotic administration [11].
in adequate amounts, confer a health benefit on the host’. The variety of probiotics products on the market is vast. They may be differentiated
What influence do bacteria have over IBS symptoms?
from each other in a number of important ways: strain specificity (not all Lactobacilli acidophilus species are exactly the same and therefore do not
• Visceral pain
behave the same), single-species (just one type of bacteria), multi-strain
• Motility
(this often refers to not only multiple strains, but multiple species and even multiple genus formulations), concentration (e.g. - 100 million to 100 billion CFU), and whether they are alone or in company with prebiotics
What role do bacteria play in visceral hypersensitivity? Animal studies have shown that development in germ-free conditions (an absence of bacterial colonisation in the gut) leads to visceral hypersensitivity [12], which may be normalised by the later introduction of gut microbes, thus providing evidence that bacterial colonisation is required for normal development of nociceptive physiology. A recent study also showed that colonic hypersensitivity can be transferred to rats through faecal transplants from IBS patients [13]. Visceral hypersensitivity is a salient pathophysiological feature of IBS which may involve disruption in any, or all, of immune, neural, endocrine, and metabolic processes [1]. Immune pathways may be triggered
(non-digestible fiber); known as symbiotics. Clinical studies in IBS with probiotics, using a range of single-strain and multi-strain preparations, have had variable results in alleviating symptoms [20]. However a 2015 meta-analysis published in the World Journal of Gastroenterology included 24 clinical trials concluded that probiotics were more beneficial than placebo in reducing pain and symptom severity scores[21]. A more recent systematic review analysed the findings of 35 randomised controlled trials: 16 single-strain and 19 multi-strain [22]. Of the studies that found a statistically significant improvement in ‘global symptoms’ (14 out of 29 studies), and a clinically meaningful improvement in ‘abdominal pain’ (only 8 of all 35 trials), the majority were multi-strain products. Interestingly only multi-strain trials found a clinically meaningful improvement in quality of life in IBS patients.
by increased intestinal permeability, a prevalent feature of IBS-D that corresponds to the severity of symptoms [14]. Interestingly a multi-strain probiotic was shown to significantly reduce intestinal permeability in patients with IBS-D [15]. In a further trial IBS patients were found to have an abnormal, pro-inflammatory, IL-10/IL-12 ratio, which was normalized, GASTROENTEROLOGY TODAY - AUTUMN 2017
in conjunction with symptom alleviation, by consumption of the probiotic Bifidobacterium infantis [16]. Neural mechanisms involved in visceral pain perception also seem to be influenced by certain bacterial species, such as the induction of µ-opioid and cannabinoid receptors by Lactobacillus acidophilus [3].
How do bacteria affect GI motility? Disruption of intestinal motility, and resultant alterations in defecatory patterns, is a cardinal feature of IBS. The relationship between bacteria and intestinal motility is seen in intriguing research into Toll-like receptors (TLR) which are known to control intestinal epithelial homeostasis. TLR4 detects lipopolysaccharide (LPS), a major outer membrane component of Gram-negative bacteria, and in TLR4 mutant, and TLR4 knock-out
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“‘Based on current evidence it seems that multi-strain probiotics offer the best chance of improving abdominal pain, global symptoms, and crucially, quality of life in IBS sufferers”
COMPANY NEWS Conclusions The role that bacteria play in the pathogenesis of IBS may be substantial; however this relationship is extraordinarily complex and
[13] L. Crouzet et al., “The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota,” Neurogastroenterol. Motil., vol. 25, no. 4, pp. 1–11, 2013. [14] Q. Zhou, “Intestinal Membrane Permeability and Hypersensitivity In
certainly involves numerous mechanisms which remain to be fully
the Irritable Bowel Syndrome,” Pain, vol. 146, no. 614, pp. 41–46,
elucidated. Future research in this field requires statistically robust,
2009.
randomised controlled trials, with the ability to more definitively show
[15] J. Zeng, Y. Q. Li, X. L. Zuo, Y. B. Zhen, J. Yang, and C. H. Liu,
the clinical effectiveness of different probiotic preparations in the
“Clinical trial: Effect of active lactic acid bacteria on mucosal barrier
management of IBS. Based on current evidence it seems that multi-
function in patients with diarrhoea-predominant irritable bowel
strain probiotics offer the best chance of improving abdominal pain,
syndrome,” Aliment. Pharmacol. Ther., vol. 28, no. 8, pp. 994–1002,
global symptoms, and crucially, quality of life in IBS sufferers.
2008. [16] L. O’Mahony et al., “Lactobacillus and Bifidobacterium in irritable
Bibliography [1] P. J. Kennedy, “Irritable bowel syndrome: A microbiome-gut-brain axis disorder?,” World J. Gastroenterol., vol. 20, no. 39, p. 14105, 2014. [2] S. Wilson, L. Roberts, A. Roalfe, P. Bridge, and S. Singh, “Prevalence of irritable bowel syndrome: a community survey.,” Br. J. Gen. Pract., vol. 54, no. 504, pp. 495–502, 2004. [3] E. M. M. Quigley, “Gut bacteria in health and disease.,” Gastroenterol. Hepatol. (N. Y)., vol. 9, no. 9, pp. 560–9, 2013. [4] M. Thabane and J. K. Marshall, “Post-infectious irritable bowel syndrome,” World J. Gastroenterol., vol. 15, no. 29, pp. 3591–3596, 2009. [5] M. Pimentel et al., “Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects,” PLoS One, vol. 10, no. 5, pp. 1–12, 2015. [6] I. Aziz, H. Törnblom, and M. Simrén, “Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome,” Curr. Opin. Gastroenterol., vol. 33, no. 3, p. 1, 2017. [7] A. E. Perez-Cobas, “Gut microbiota disturbance during antibiotic therapy: A multi-omic approach,” Gut Microbes, vol. 5, no. 1, pp.
bowel syndrome: Symptom responses and relationship to cytokine profiles,” Gastroenterology, vol. 128, no. 3, pp. 541–551, 2005. [17] M. Anitha, “Gut microbial products regulate murine gastrointestinal motility via Toll-like Receptor 4 signaling,” Gastroenterology, vol. 143, no. 4, pp. 1006–1016, 2012. [18] E. K. Brint, J. MacSharry, A. Fanning, F. Shanahan, and E. M. M. Quigley, “Differential Expression of Toll-Like Receptors in Patients With Irritable Bowel Syndrome,” Am. J. Gastroenterol., vol. 106, no. 2, pp. 329–336, 2011. [19] E. F. Verdú et al., “Lactobacillus paracasei normalizes muscle hypercontractility in a murine model of postinfective gut dysfunction,” Gastroenterology, vol. 127, no. 3, pp. 826–837, 2004. [20] M. E. Sanders et al., “An update on the use and investigation of probiotics in health and disease.,” Gut, vol. 62, no. 5, pp. 787–96, 2013. [21] T. Didari, “Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis,” World J. Gastroenterol., vol. 21, no. 10, p. 3072, 2015. [22] Y. A. McKenzie, J. Thompson, P. Gulia, and M. C. E. Lomer, “British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update),” J. Hum. Nutr. Diet., vol. 29, no. 5, pp. 576–592, 2016.
64–70, 2014. [8] J. Goldenberg and J. B. Lytvyn L, Steurich J, Parkin P, Mahant S, “Probiotics for the prevention of pediatric antibiotic-associated diarrhea ( Review ),” Cochrane Database Syst Rev., vol.
[9] S. M. O’Mahony et al., “Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses,” Biol. Psychiatry, vol. 65, no. 3, pp. 263–267, 2009. [10] P. R. Maxwell, E. Rink, D. Kumar, and M. A. Mendall, “Antibiotics increase functional abdominal symptoms,” Am. J. Gastroenterol., vol. 97, no. 1, pp. 104–108, 2002. [11] E. F. Verdú et al., “Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice.,” Gut, vol. 55, no. 2, pp. 182–90, 2006. [12] P. Luczynski et al., “Microbiota regulates visceral pain in the
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:CD004827., no. 12, pp. 1–49, 2015.
mouse,” Elife, vol. 6, pp. 1–21, 2017.
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COMPANY NEWS
H. PYLORI, CLOTEST AND A PIONEERING STOREY OF SELF-EXPERIMENTATION… The CLOtest* Rapid Urease Test is recognised by medical professionals as the “Gold Standard” among urease tests because of its accuracy, convenience and affordability. Developed by Barry Marshall, M.D. who, along with Robin Warren, M.D., was the first to discover the correlation between Helicobacter pylori (H. pylori) and gastric ulcers. The name of the test originated from “Campylobacter-Like Organism” when Drs. Warren and Marshall first cultured the bacterium from antral biopsies in 1982. Subsequently, the genus was named Helicobacter, meaning spiral or helical bacteria due its spiral-shaped appearance. H. pylori has been shown to cause active chronic gastritis and is a risk factor for gastric cancer and mucosal-associated-lymphoid-type (MALT) lymphoma. The eradication of H. pylori is effective in eliminating or reducing the recurrence of ulcers and may also lower the risk of gastric cancer. In a recent article+ in The Biomedical Scientist Dr Marshall recounted to George Winter how in late July 1984 working as a Microbiology Registrar in Freemantle Australia, he consumed a cocktail containing 109 colony forming units of H. pylori, an act which would ultimately change our understanding of medicine. Three years earlier Dr Robin Warren was working as a Pathologist at Royal Perth Hospital, Western Australia and was examining histological sections from gastritis patients. What he saw was spiral-shaped bacteria in a stomach biopsy sample from a patient with non-ulcer dyspepsia. Drs Marshall and Warren began a collaboration to investigate the organism. Initial attempts to grow the bacterium failed due to faulty equipment and failure to incubate long enough but after an extended holiday weekend in April 1982, colonies were seen for the first time. After some initial scepticism, the realisation
GASTROENTEROLOGY TODAY - AUTUMN 2017
28
that a major breakthrough in understanding was ‘just around the corner’ began to dawn. Later that year Drs Marshall and Warren began a prospective investigation in 100 consecutive patients undergoing endoscopy. The results showed that 65% of the patients had gastritis and there was strong association between the spiral bacteria and gastritis and all patients with duodenal ulcers with 80% of those with gastric ulcers presenting with the organism. The cause of peptic ulcers was now evident. Assessment of this work and other subsequent studies around the world, established the percentage of patients with duodenal ulcers positive for H. pylori to be about 92%. Drs Marshall and Warren went on to suggest that the bacterium causing stomach ulcers in patients could be treated with antibiotics which was a real challenge to the medical establishment of the time. Without an established animal model to demonstrate cause and effect Dr Marshall considered the options which led to the famous self-experiment in late July 1984. From cultures growing in the laboratory, on a Monday morning Dr Marshall drank a beef broth laced with the helical bacterium. Five days later Dr Marshall had developed bad breath, nausea and recurrent vomiting of acid-free gastric juice. A gastric biopsy after 10 days showed acute gastritis and the presence many H.pylori and the cause of the inflammation. A course of antibiotics was administered to subdue the infection. The publication which followed changed medical thinking concerning the cause and treatment of stomach ulcers with the US National Institutes of Health (NIH) in 1994 recommending that patients exhibiting H. pylori infection should be in future treated with antimicrobial agents. Many honours followed culminating in 2005 with the Nobel Prize being awarded in Physiology and Medicine. 35 years later H.pylori is now understood to be the most common infection known to man and a major source of stomach cancer. The achievement of Drs Marshall and Warren is now recognised around the world. Today CLOtest Rapid Urease Test has become the most widely used rapid urease test worldwide for the diagnosis of H. pylori. One of the most common chronic infections worldwide, H. pylori is associated with 95% of duodenal ulcers and 80% of gastric ulcers. Clinical studies have shown that eradicating H. pylori is effective in eliminating or reducing the recurrence of ulcers and may also lower the risk of gastric cancer. The National Institutes of Health recommends testing for H. pylori in all patients with gastric or duodenal ulcers. CLOtest has a well of urease indicator gel sealed inside a plastic slide. If the urease from H. pylori is present in the tissue biopsy sample, it changes the gel from yellow to bright magenta and this colour change is indicative of the presence of H. pylori.
* Registered Trademark or Trademark of Halyard Health, Inc +
rticle by George F Winter journalist, author and Fellow of the IBMS, A Writing in The Biomedical Scientist, May issue 2017.
COMPANY NEWS
INHEALTH FIRST TO DELIVER COMMUNITY ENDOSCOPY SERVICES UNDER THE NEW “2 WEEK WAIT” CANCER PATHWAY InHealth Endoscopy is set to expand its existing ‘straight to test’ community endoscopy service in Oxfordshire having been awarded a significant contract by Oxfordshire CCG. As the current provider delivering services to the local population for over 5 years from its JAG accredited unit in Witney, the service will be expanding with the opening of 2 new locations in Oxfordshire by Spring 2018, and will be the first independent provider to deliver services under the new “2 week wait” pathway.
InHealth Endoscopy has led the development of “straight to test” community endoscopy for over 26,000 patients last year in the UK, offering innovations such as trans nasal endoscopy with low levels of sedation. InHealth Clinical lead for Oxfordshire and Gloucester, Tim Healy, also commented “Our routine upper and lower GI service is well established in West Oxfordshire and with trans nasal endoscopy we uniquely offer a minimally invasive service which doesn’t require sedation and offers patients a much more comfortable experience.“ Richard Bradford, CEO of InHealth, said: “InHealth’s service in Oxfordshire is highly regarded by GPs and achieves over 99% on the Friends and Family test. This expansion provides us with an opportunity to improve clinical outcomes which exceed the JAG and BSG requirements, and meet the latest standards for patient comfort, privacy and dignity.”
GASTROENTEROLOGY TODAY - AUTUMN 2017
“InHealth’s service in Oxfordshire is highly regarded by GPs and achieves over 99% on the Friends and Family test. This expansion provides us with an opportunity to improve clinical outcomes which exceed the JAG and BSG requirements, and meet the latest standards for patient comfort, privacy and dignity.”
Ben Peregrine, Regional Operations Manager at InHealth said “Aside from our existing reputation for quality and improvement, we were able to demonstrate our ability to support Oxfordshire CCG in their objectives to improve local access, bring care closer to home, improve cancer outcomes, reduce delays in diagnostic pathways and integrate care pathways between providers. By working closely with primary care clinicians and commissioners we support the management of the patients within the community, allowing secondary care services to spend more time concentrating on complex pathology and serious investigations.”
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COMPANY NEWS
ALLERGAN’S TRUBERZI®▼ (ELUXADOLINE) RECEIVES FINAL APPROVAL FROM NICE FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME WITH DIARRHOEA (IBS-D) IN ADULTS Truberzi® now funded by the NHS, becomes the first IBS-D treatment reviewed and recommended by NICE in a Technology Appraisal Guidance* (TA471)
The Final Guidance recommends Truberzi® for patients whose IBS-D has not responded to other treatments routinely used for IBS-D (or who cannot tolerate or are contraindicated to such treatments) and that treatment is initiated in hospital.1
Marlow, UK, 30 August, 2017, Allergan announced that the National Institute of Health and Care Excellence (NICE) has published Final
Dr Adam Farmer, Consultant Gastroenterologist at University
Guidance, with the positive recommendation that Truberzi® (eluxadoline)
Hospitals of North Midlands and Scientific Advisor at The IBS
be made available on the National Health Service for adults living with
Network, the UK’s national charity for IBS said, “Until now doctors
Irritable Bowel Syndrome with Diarrhoea (IBS-D) .
have had limited options when it comes to treating IBS-D and
Truberzi is a first-in-class, twice daily, oral medication offering sustained
whom endure debilitating symptoms on a daily basis. For doctors
1
unfortunately this has been to the detriment of patients, many of
®
relief from multiple symptoms of IBS-D, such as pain, diarrhoea, urgency and bloating2,3. In two pivotal Phase III trials, Truberzi® demonstrated a significant reduction in the two most bothersome symptoms of IBS-D, abdominal pain and diarrhoea, with fast and sustained relief for over six months. Treatment effect can be seen within 1 week, reaches maximal effect after 6 weeks and is sustained over 6 months.
2,3,4
to now be able to prescribe Truberzi®, a targeted treatment, this will signify real change for IBS-D sufferers. I am very much looking forward to seeing my patients reap the benefits”. Nicola Massey, Country Manager, Allergan UK & Ireland, said “Allergan is delighted that NICE has provided final positive guidance for Truberzi®. We understand the profound impact that IBS-D can have on sufferers and are extremely proud to be offering patients, via the NHS, the first IBS-D treatment with a positive NICE TAG.” References *TAG - Technology appraisals are recommendations on the use of new and existing medicines and treatments within the NHS.
GASTROENTEROLOGY TODAY - AUTUMN 2017
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1. https://www.nice.org.uk/ guidance/ta471 (last accessed 30 August, 2017) 2. Lembo AJ, et al. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med 2016; 374:242-253 3. TRUBERZI® (eluxadoline) Summary of Product Characteristics. Last Accessed July 2017 4. American Gastroenterological Association survey. (2015). IBS in America” Summary Survey Findings. Available at: http:// ibsinamerica.gastro.org/files/ IBS_in_America_Survey_ Report_2015-12-16.pdf. Last accessed September 2016.
COMPANY NEWS
TREATMENT OF CIBD NOW EASIER WITH METHOTREXATE IN AUTO-INJECTOR New: metoject® PEN approved for treatment of Crohn’s disease in Europe
syringe and pre-filled pen is particularly suitable. Moreover, in patients
References 1. SPC (UK) Metoject PEN solution for injection in pre-filled pen. National version: 01/2017. 2. Gomollón F et al. ECCO Guideline/Consensus Paper. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management Journal of Crohn’s and Colitis. 2017, 3–25. 3. Müller-Ladner U et al. Tolerability and patient/physician satisfaction with subcutaneously administered methotrexate provided in two formulations of different drug concentrations in patients with rheumatoid arthritis. Open Rheumatol J. 2010;4:15-22; Demary W et al. Subcutaneously administered methotrexate for rheumatoid arthritis by pre-filled syringes versus pre-filled pens: patient preference and comparison of self-injection experience. Patient Prefer Adherence. 2014;8:1061-71; Pachon JA et al. Assessing usability, label comprehension, pen robustness and pharmacokinetics of a self-administered prefilled autoinjector pen of methotrexate in patients with rheumatoid arthritis. SAGE Open Medicine 2014;2:2050312114564241. 4. Cesarini M et al. Methotrexate in Crohn’s disease: a new face for an old drug? Expert Rev Gastroenterol Hepatol. 2016;10:1135-44; Thomas SS et al. Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis. BioDrugs. 2015;29:241-58.
with rheumatism, both the high concentration of the active substance
* Availability is country specific
Medac Gesellschaft für klinische Spezialpräparate mbH has announced that methotrexate has been approved for treatment of Crohn’s disease with immediate effect in a pre-filled pen, the metoject®/metex®PEN 50 mg/ml solution for injection.1 The auto-injector makes it easier to administer subcutaneous methotrexate (MTX), the use of which is established in rheumatological and dermatological treatment, and thus helps to ensure patient compliance. Apart from the auto-injector, Medac provides a pre-filled syringe with MTX (i.e. metoject®/metex®) an as well patient-oriented pharmaceutical form that is approved for gastroenterology treatment. The methotrexate auto-injector satisfies patients’ needs Based on the treatment recommendation in European guidelines of 25 mg parenteral methotrexate per week initially, followed by 15 mg per week in the long term2, the use of subcutaneous MTX in a pre-filled
(50 mg/ml) in the Medac preparations and the handling with the Medac auto-injector have proven superior.3 Methotrexate as a combination partner In addition to the known corticosteroid-sparing effect of MTX treatment, the subject of methotrexate as a combination partner of biotechnological medicinal products should years, a growing number of publications have investigated and described the positive properties of methotrexate with regard to the reduced rate of antibody development when combined with biologicals.4 The metoject®/metex® PEN is available in a total of ten different dosages* (7.5 mg / 10 mg / 12.5 mg / 15 mg / 17.5 mg / 20 mg / 22.5 mg / 25 mg / 27.5 mg / 30 mg).
GASTROENTEROLOGY TODAY - AUTUMN 2017
receive more attention. In recent
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Helicobacter Test INFAI ® The most used 13C-urea breath test for the diagnosis of Hp-infection worldwide
• more than 4.5 million INFAI tests performed in Europe • approved for children from the ages of 3 to 11 • special INFAI test for patients with dyspepsia taking PPIs • cost-effective CliniPac Basic version for hospital use INFAI Institute for Biomedical Analysis & NMR Imaging, INFAI UK Ltd Innovation Centre, University Science Park, University Road, Heslington, YORK YO10 5DG, UK Phone +44 1904 435 228 - Fax +44 1904 435 229 - mail: info@infai.co.uk - Visit us at www.infai.com