Gastroenterology Today Summer 2021
Gastroenterology Today Summer 2021
Gastroenterology Today Summer 2021
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Volume 31 No. 2<br />
<strong>Summer</strong> <strong>2021</strong><br />
<strong>Gastroenterology</strong> <strong>Today</strong><br />
What approach has 18 Week Support<br />
taken with regards to building an<br />
expert insourcing team?<br />
Matthew’s Perspective:<br />
Dr Matthew Banks is the Clinical Director for 18 Week Support <strong>Gastroenterology</strong>. He believes it starts with recruiting the<br />
best clinicians. ‘At 18 Week Support we set the bar very high. We only recruit clinicians whose JAG performance data is well<br />
above the national standards. In addition, we monitor each clinician’s KPIs while they work with 18 WS. While the JAG data<br />
is an excellent quality indicator, we now want to go a step beyond that and monitor the Non-Technical skills (NTS) of each<br />
clinician as well. We now know that NTS plays an important role in safe and effective team performance. Therefore, in our<br />
quest to develop excellent teams who deliver a world-class service, we must focus on NTS’.<br />
Tammy and Lisa’s Perspective:<br />
Tammy Kingstree is Lead Nurse for Endoscopy.<br />
‘It is extremely important that there are good working relationships within the team. This starts with strong leadership from<br />
our senior nurse coordinators who are trained to manage the patient pathway, manage a team of staff they may not know<br />
and to deal effectively with any issues which may arise on the day’.<br />
Lisa Phillips is Lead Nurse for Endoscopy.<br />
‘The team objectives are clear. Excellent patient experience and good patient outcomes. Because the objectives are clear,<br />
team cohesion and focus are exceptionally good. It therefore shouldn’t matter that we are in an unfamiliar endoscopy unit,<br />
the service should be seamless. If it isn’t, we do not stop until we get it right.<br />
If you have an excellent NHS record and want to help clear NHS waiting list backlogs, reduce RTT waiting times and provide<br />
18 Week Support <strong>Gastroenterology</strong>:<br />
Partnering to Succeed<br />
high-quality patient care, get in touch by calling on 020 3892 6162 or email Gastro.Recruitment@18weeksupport.com<br />
Dr Matthew Banks<br />
Clinical Lead for <strong>Gastroenterology</strong>
H<br />
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CONTENTS<br />
CONTENTS<br />
<strong>Gastroenterology</strong> <strong>Today</strong><br />
4 EDITORS COMMENT<br />
6 FEATURE Encouraging Uptake of Faecal Immunochemical<br />
Tests (FIT) in Assessment of Patients with<br />
Lower Bowel Symptoms<br />
12 FEATURE Diagnosis and management of coeliac disease<br />
in specialist paediatric gastroenterology centres<br />
in the UK<br />
14 FEATURE The incidence and prevalence of inflammatory<br />
Matthew’s Perspective:<br />
bowel disease in UK primary care: a<br />
retrospective cohort study of the IQVIA Medical<br />
Research Database<br />
20 CASE REPORT Heavy metal in the gastroenterology clinic<br />
22 CASE REPORT Infliximab-induced seizures in a patient<br />
with Crohn’s disease: a case report<br />
26 NEWS<br />
30 COMPANY NEWS<br />
This issue edited by:<br />
Hesam Ahmadi Nooredinvand<br />
c/o Media Publishing Company<br />
Greenoaks<br />
Lockhill<br />
Upper Sapey, Worcester, WR6 6XR<br />
What approach has 18 Week Support<br />
taken with regards to building an<br />
expert insourcing team?<br />
ADVERTISING & CIRCULATION:<br />
Media Publishing Company<br />
Greenoaks, Lockhill<br />
Upper Sapey, Worcester, WR6 6XR<br />
Tel: 01886 853715<br />
E: info@mediapublishingcompany.com<br />
www.MediaPublishingCompany.com<br />
Dr Matthew Banks is the Clinical Director for 18 Week Support <strong>Gastroenterology</strong>. PUBLISHING He believes it starts DATES: with recruiting the<br />
best clinicians. ‘At 18 Week Support we set the bar very high. We only recruit March, clinicians June, whose JAG September performance data and is well December.<br />
above the national standards. In addition, we monitor each clinician’s KPIs while they work with 18 WS. While the JAG data<br />
is an excellent quality indicator, we now want to go a step beyond that and monitor the Non-Technical skills (NTS) of each<br />
COPYRIGHT:<br />
clinician as well. We now know that NTS plays an important role in safe and effective team performance. Therefore, in our<br />
quest to develop excellent teams who deliver a world-class service, we must Media focus on Publishing NTS’. Company<br />
Greenoaks<br />
Tammy and Lisa’s Perspective:<br />
Lockhill<br />
Tammy Kingstree is Lead Nurse for Endoscopy.<br />
‘It is extremely important that there are good working relationships within Upper the team. Sapey, This starts with Worcester, strong leadership WR6 from 6XR<br />
our senior nurse coordinators who are trained to manage the patient pathway, manage a team of staff they may not know<br />
and to deal effectively with any issues which may arise on the day’.<br />
Lisa Phillips is Lead Nurse for Endoscopy.<br />
PUBLISHERS STATEMENT:<br />
The views and opinions expressed in<br />
this issue are not necessarily those of<br />
the Publisher, the Editors or Media<br />
Publishing Company.<br />
‘The team objectives are clear. Excellent patient experience and good patient outcomes. Because the objectives are clear,<br />
team cohesion and focus are exceptionally good. It therefore shouldn’t matter that we are in an unfamiliar endoscopy unit,<br />
the service should be seamless. If it isn’t, we do not stop until we get it right.<br />
If you have an excellent NHS record and want to help clear NHS waiting list backlogs, reduce RTT waiting times and provide<br />
high-quality patient care, get in touch by calling on 020 3892 6162 or email Next Gastro.Recruitment@18weeksupport.com<br />
Issue Autumn <strong>2021</strong><br />
COVER STORY<br />
In this edition we explore developments in CPD and education, in particular<br />
how digital learning is contributing to the further development of technical<br />
skills, diagnosis and disease management in endoscopy, all of which are vital<br />
to quality, safety and efficiency.<br />
Our JAG quality standards generally exceed the UK average (National<br />
Endoscopy Database) but obviously no health organisation can afford to rest<br />
on its’ laurels when it comes to quality and safety. This is why we have recently<br />
partnered with GastroLearning, an endoscopic educational platform pioneered<br />
by University College London consultants that delivers high-quality CPD and<br />
educational content digitally.<br />
All practitioners registered with 18 Week Support can access GastroLearning’s<br />
education channels and content free of charge. In this post-pandemic world<br />
the provision of education is changing fast. Formal conferences will continue<br />
to have their place, but medical practitioners are increasingly switching to<br />
content delivered across multiple digital channels that is directly relevant to<br />
their need and which can be accessed at a time which best suits their busy<br />
working lives. Read the article to see more about the content provided and<br />
how it delivered free to any practitioner joining us here at 18 Week Support.<br />
Subscription Information – <strong>Summer</strong> <strong>2021</strong><br />
<strong>Gastroenterology</strong> <strong>Today</strong> is a quarterly<br />
publication currently sent free of charge to<br />
all senior qualified Gastroenterologists in<br />
the United Kingdom. It is also available<br />
by subscription to other interested individuals<br />
and institutions.<br />
UK:<br />
Other medical staff - £18.00 inc. postage<br />
Non-medical Individuals - £24.00 inc. postage<br />
Institutions<br />
Libraries<br />
Commercial Organisations - £48.00 inc. postage<br />
Rest of the World:<br />
Individuals - £48.00 inc. postage<br />
Institutions<br />
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We are also able to process your<br />
subscriptions via most major credit<br />
cards. Please ask for details.<br />
Cheques should be made<br />
payable to MEDIA PUBLISHING.<br />
Designed in the UK by me&you creative<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
3
EDITORS COMMENT<br />
EDITORS COMMENT<br />
“The<br />
pandemic<br />
has<br />
dramatically<br />
changed our<br />
practice. One<br />
such change<br />
has been a<br />
shift toward<br />
remote<br />
consultations<br />
which is, at<br />
least in part,<br />
here to stay.”<br />
The incredible success of the COVID 19 vaccination has given us all hope. Although<br />
most would agree this virus, like almost all others, will likely never be fully eradicated,<br />
the success of the vaccination programme has meant a greater degree of freedom as we<br />
gradually exit from lockdown. COVID 19 has not only affected the lives of our patients’<br />
both physical and psychological wellbeing over the past sixteen months but the collateral<br />
damage it has inflicted will likely be experienced for years to come. The measure of<br />
the true impact of this is yet to be fully appreciated but given the reduction in access<br />
to healthcare, it is inevitable that the delay in diagnosis and treatment is resulting in<br />
increased morbidity and mortality for many patients particularly the elderly and those with<br />
chronic conditions.<br />
The pandemic has dramatically changed our practice. One such change has been a<br />
shift toward remote consultations which is, at least in part, here to stay. This does not<br />
only have the potential to improve the financial efficiency of our services but also many<br />
patients prefer this to face to face consultation given the cost and inconvenience of travel.<br />
Its success will however depend on being able to identify the group of patients for whom<br />
remote consultation is appropriate and optimal as well as addressing digital literacy issues<br />
particularly in the elderly.<br />
Hesam Ahmadi Nooredinvand,<br />
St George’s Hospital<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
4
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as part of an expert clinical team in outpatient clinics or<br />
undertaking Endoscopy procedures, getting the right care<br />
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Register your support or enquire below.<br />
Together, we can end the wait.<br />
www.ukmedinet.com
FEATURE<br />
ENCOURAGING UPTAKE OF FAECAL<br />
IMMUNOCHEMICAL TESTS (FIT) IN ASSESSMENT<br />
OF PATIENTS WITH LOWER BOWEL SYMPTOMS<br />
Keywords: Faecal immunochemical test (FIT), COVID-19, bespoke, FIT-KIT, triaging, endoscopy, waiting time.<br />
Abstract<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
6<br />
In April 2020, all non-urgent endoscopy procedures were<br />
suspended due to the COVID-19 pandemic. Consequently,<br />
those referred for colorectal cancer (CRC) investigation in<br />
England under the NG12 1 and DG30 2 guidelines faced increasing<br />
waiting times. It became necessary to triage these patients to<br />
allocate resources effectively. However, the pandemic makes<br />
patient contact challenging, reducing the number of face-toface<br />
consultations to minimise the spread of COVID-19. Faecal<br />
immunochemical tests (FIT) offer a unique solution since the<br />
process can be managed “contact free”, reducing risk to patients<br />
and health workers. Faecal sample collection by patients is still<br />
novel, compared to other sample collection methods such as<br />
for blood tests. However, patients are often reluctant to handle<br />
faecal samples. A solution must, therefore, have a patient-centred<br />
approach to encourage sample collection and return, while<br />
ensuring good quality samples for analysis. The answer lies<br />
in the provision of bespoke patient literature. Trust and Health<br />
Board specific leaflets with local phone numbers, QR-codes,<br />
barcodes, and clear visuals, with non-clinical instructional text,<br />
provide much needed support to FIT pathways which, in turn, has<br />
aided the management of endoscopy waiting lists. The bespoke<br />
leaflets result in noticeable increases in return rates, and the<br />
quality of samples received by laboratories are also much<br />
improved.<br />
The onset of the COVID-19 pandemic caused widespread disruption to<br />
many clinical diagnostic pathways. Already overburdened endoscopy<br />
services faced considerable reductions, resulting in fewer procedures<br />
and, in consequence, fewer diagnoses of colorectal cancer (CRC) and<br />
other significant bowel diseases. CRC is highly treatable if detected in<br />
its early stages 3 and long-term quality of life is much improved following<br />
successful treatment. However, the waiting times for endoscopy have<br />
resulted, and still are resulting, in concerning delays to diagnosis 4 .<br />
Therefore, a supporting pathway is a necessary prerequisite to alleviate<br />
pressure on the service and prioritise those with the most severe<br />
symptoms for further investigation.<br />
Use of FIT<br />
It is widely appreciated that FIT is the ideal tool to use, not only to<br />
continue supporting the existing primary care pathways, as guided by<br />
NICE NG12 1 and DG30, 2 but also for use in secondary care and triaging<br />
patients on waiting lists. National guidelines published in both England 5<br />
and Scotland 6 outline how FIT can be used to support CRC referrals in<br />
the pandemic, by using higher faecal haemoglobin concentration (f-Hb)<br />
thresholds than that recommended originally for the low-risk cohort<br />
under DG30. 2<br />
The f-Hb is proportional to the risk of severe disease and has been<br />
proven to be a valuable marker even in those referred with rectal<br />
bleeding 7 , suggesting that FIT is suitable in both high- and low-risk<br />
patient groups. This is further supported by recent diagnostic accuracy<br />
studies, highlighting that the negative predictive value (NPV) for CRC<br />
is over 98.9% 8 even when using a high threshold of 150 µg Hb/g<br />
faeces. Other possible thresholds for investigation have been very<br />
recently documented in detail 9 . However, ubiquitous use of FIT in the<br />
triage for further investigation of patients presenting with symptoms<br />
is still relatively novel in terms of sample collection and logistics, so,<br />
while technically FIT is a suitable test, its application must be carefully<br />
managed to ensure the issues with overburdened services are resolved,<br />
and not just relocated.<br />
Managing Remote Sample Collection<br />
GP consultations dropped by 30% between the end of March and end<br />
of May 2020 10 , and primary care is the most common starting point<br />
for referral for patients with suspected CRC. With this decrease, there<br />
was concern surrounding the use of FIT and how well clinical pathways<br />
could be supported. To address this, innovative logistics strategies<br />
were required because good engagement is a key driver to motivating<br />
patients to collect and sample faeces and return these samples for<br />
analysis. Since telephone and video consultations increased sharply, it<br />
was considered that the FIT sample collection device and instructions<br />
for use, could be posted out to the patient, as well as being collectable<br />
at the GP surgery. After the sample is collected by the patient, the<br />
device is either posted back to the laboratory or dropped off at the GP<br />
surgery for onward transport. These approaches make the complete<br />
process between consultation and the generation of a result “contact<br />
free” and therefore considerably reduces the risk of spreading<br />
COVID-19. With the sample collection, handling, transport, and<br />
other logistics now in place, encouraging correct use is clearly a vital<br />
consideration.<br />
Maximising Uptake<br />
With such reliance on samples collected by patients, uptake is vital. With<br />
faecal samples, there are the associated “fear” and “disgust” factors<br />
which deter some patients from collecting the sample, in spite of the
FEATURE<br />
simple, easy to use, hygienic FIT sample collection devices. However,<br />
bespoke instruction for use (IFU) leaflets have been hugely influential in<br />
increasing uptake and improving sample quality. Such IFU are based<br />
around core sampling requirements but adapted to suit the specific<br />
clinical pathway adopted by Trusts and Health Boards. With local<br />
contact numbers, bar-codes, and detailed pathway information, patients<br />
are made to feel included in the diagnostic process and are provided<br />
with the tools to complete the sample collection successfully or talk to a<br />
knowledgeable professional should they have any questions. IFU have<br />
evolved over time, after initially being used in primary care, FIT is now<br />
being used in a more diverse range of patients, 11 so the detail must be<br />
regularly reviewed to ensure suitability. Usability studies, consultation<br />
events, focus groups and feedback from cancer charities all could<br />
contribute to the design and production of these IFU to maximise the<br />
inclusivity of the process.<br />
The design and application of sample collection devices are suited<br />
to patient-based sampling and, although the attributes will not be<br />
discussed in detail here, research has been conducted on the efficacy<br />
of FIT in the hands of patients, 12,13 , proving them suitable for this<br />
application. Additionally, the IFU provide supporting information such<br />
as tips for collecting the faeces prior to using the device, which helps<br />
familiarise using faeces as a sample and helps break some of the<br />
barriers to the sampling process. It also helps reduce contamination risk<br />
in terms of the faecal sample, and the sample collection device.<br />
FIT for All<br />
The last, and possibly most critical, barrier to uptake, is ensuring the IFU<br />
are suitable for a range of patient groups. With FIT now being used in a<br />
diverse range of patients, the bespoke literature must be as inclusive as<br />
possible, ensuring patients can understand and follow the instructions.<br />
As discussed above, the use of simple colourful pictures or diagrams<br />
and text help those with visual impairments, or those for whom English<br />
is not a primary language, and the additional information provided, such<br />
as phone numbers, links to videos and websites, provide more routes<br />
for patients to access help should this be required. It is important to<br />
consider that a FIT device should not be simply handed to a patient with<br />
no advice: as part of the safety-netting process, FIT should be provided<br />
following a discussion with the patient.<br />
Large, full-colour pictures with accompanying text provide patients<br />
with user-friendly guidelines on the collection of faeces, using the<br />
sample collection device to take the sample, and then how to return it<br />
for analysis. Additional information should be provided on the clinical<br />
pathway, why the test has been requested, and who to contact if<br />
the patient has questions. These personalised aspects reduce the<br />
unpleasantness associated with faecal sample collection. Their<br />
introduction has resulted in an increase in return rate facilitating a<br />
service to maximise impact and alleviate some waiting times.<br />
Quality Samples<br />
Any pathway involving a patient collected sample must yield samples<br />
suitable for analysis. With FIT, there has been much scrutiny over the<br />
use of a patient utilised sample collection device and the possible<br />
impact on the laboratory result and, therefore, on patient outcome. The<br />
primary consideration here is that FIT should never be used in isolation<br />
and should be a tool applied in conjunction with clinical suspicion<br />
and adjunct tests including the full blood count and iron studies when<br />
appropriate, to further reduce the risk of missing CRC, particularly in<br />
complex patients on waiting lists. 11<br />
Concerns around patient sampling include over-sampling, undersampling<br />
(or even, not sampling at all and providing an unused device<br />
for testing). Contaminating the faeces prior to sampling with, for<br />
example, menstrual blood and toilet cleaners can also be an issue.<br />
To ensure continued relevance in the pathway, IFU are continuously<br />
reviewed. Involvement with patients, key opinion leaders, and<br />
feedback from laboratories all contribute to the ongoing improvement<br />
programmes. Ensuring fidelity to the Trust or Health Board’s specific<br />
clinical pathway helps the laboratories manage the samples effectively,<br />
reducing the risk of overburdening the analytical capability. Feedback<br />
is positive, with many reports showing over 90% of patients have been<br />
able to follow the IFU and use the device as intended. 14<br />
Logistics<br />
The initiation of the use of FIT following the design of an IFU includes<br />
the logistics: some encourage the GP surgery to hold stock of the<br />
FIT-KITs (device, plus IFU, plus return envelope) so distribution is<br />
managed on a local level, whereas others (particularly those with<br />
electronic test requesting) have a centralised location from which the<br />
FIT-KITs are distributed. Both models work for their respective users,<br />
with stock management and logistics managed in a similar way to other<br />
consumables, slotting into already proven processes.<br />
Sample return logistics are also well studied. Originally, postal<br />
return services, similar to the methods used in the bowel screening<br />
programmes conducted in all four nations of the UK, was preferred,<br />
reducing the footfall in GP surgeries, and giving patients a quick and<br />
convenient sample return method. The ambient temperature stability<br />
of any haemoglobin present after collection of faeces means a postal<br />
return service would be a suitable route for sample returns. However,<br />
due to cost implications, the return of samples via the GP surgery is<br />
becoming more popular, negating the postage costs. Samples can be<br />
efficiently and effectively returned to the laboratory with other types of<br />
specimens via existing transport services. There has been no reduction<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
7
FEATURE<br />
in patient uptake in those Trusts and Health Boards that have moved<br />
from postal to GP surgery return, showing that FIT pathways can be<br />
flexible and adaptable to local requirements.<br />
Conclusion<br />
Without doubt, the COVID-19 pandemic has fundamentally changed<br />
many clinical pathways in the health service. Many hope that some of<br />
these innovative changes will continue into the future. This the widely<br />
held opinion regarding the application of FIT, and the recent expansions,<br />
past the original NG12 1 and DG30 2 guidelines, to use FIT in all patients<br />
of all ages presenting with lower bowel symptoms, has provided a<br />
clinically relevant investigation which now is a vital tool in the diagnosis<br />
and treatment of CRC. With new logistics options, patient-centric<br />
literature, and a sample collection device specifically designed for<br />
patient-based sampling, the expansion of FIT will continue to support<br />
endoscopy service for years to come, by helping avoid unnecessary<br />
procedures, and allowing urgent referral for those most at risk of<br />
significant bowel disease.<br />
FIT-KITS have been developed by Alpha Laboratories, working in<br />
collaboration with a large number of NHS and private healthcare<br />
providers across the UK. If you would like to discuss your requirements<br />
to facilitate an efficient process for rolling out FIT for your patients,<br />
please contact digestivedx@alphalabs.co.uk.<br />
With thanks to Professor Callum G Fraser, Centre for Research into<br />
Cancer Prevention and Screening, University of Dundee.<br />
References<br />
1. NICE. Suspected cancer: recognition and referral. NICE guideline<br />
[NG12]. Last updated: 29 January <strong>2021</strong>. https://www.nice.org.uk/<br />
guidance/ng12 (Accessed 19 March <strong>2021</strong>).<br />
2. NICE. Quantitative faecal immunochemical tests to guide referral<br />
for colorectal cancer in primary care. Diagnostics guidance [DG30].<br />
Published date: 26 July 2017. https://www.nice.org.uk/guidance/<br />
dg30 (Accessed 19 March <strong>2021</strong>).<br />
3. Colorectal Cancer Survival by Stage - NCIN Data Briefing. http://<br />
www.ncin.org.uk/publications/data_briefings/colorectal_cancer_<br />
survival_by_stage (Accessed 19 March <strong>2021</strong>).<br />
4. Ho KMA, Banerjee A, Lawler M, Rutter MD, Lovat LB. Predicting<br />
endoscopic activity recovery in England after COVID-19: a national<br />
analysis. Lancet Gastroenterol Hepatol <strong>2021</strong> Mar 10:S2468-<br />
1253(21)00058-3. doi: 10.1016/S2468-1253(21)00058-3. Epub<br />
ahead of print.<br />
5. https://www.england.nhs.uk/wp-content/uploads/2020/10/<br />
BM2025Pu-item-5-diagnostics-recovery-and-renewal.pdf (Accessed<br />
19 March <strong>2021</strong>).<br />
6. https://www.gov.scot/publications/coronavirus-covid-19-guidancefor-use-of-fit-testing-for-patients-with-colorectal-symptoms<br />
(Accessed 19 March <strong>2021</strong>).<br />
7. Digby J, Strachan JA, McCann R, Steele RJ, Fraser CG, Mowat C.<br />
Measurement of faecal haemoglobin with a faecal immunochemical<br />
test can assist in defining which patients attending primary care<br />
with rectal bleeding require urgent referral. Ann Clin Biochem<br />
2020;57:325-7. doi: 10.1177/0004563220935622.<br />
8. D’Souza N, Georgiou Delisle T, Chen M, Benton S, Abulafi M;<br />
NICE FIT Steering Group. Faecal immunochemical test is superior<br />
to symptoms in predicting pathology in patients with suspected<br />
colorectal cancer symptoms referred on a 2WW pathway: a<br />
diagnostic accuracy study. Gut 2020 Oct 21:gutjnl-2020-321956.<br />
doi: 10.1136/gutjnl-2020-321956. Epub ahead of print.<br />
9. Mowat C, Digby J, Strachan JA, McCann RK, Carey FA, Fraser<br />
CG, Steele RJ. Faecal haemoglobin concentration thresholds for<br />
reassurance and urgent investigation for colorectal cancer based<br />
on a faecal immunochemical test in symptomatic patients in<br />
primary care. Ann Clin Biochem <strong>2021</strong> Jan 21:4563220985547. doi:<br />
10.1177/0004563220985547. Epub ahead of print.<br />
10. https://www.health.org.uk/news-and-comment/charts-andinfographics/non-covid-19-nhs-care-during-the-pandemic<br />
(Accessed 19 March <strong>2021</strong>).<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
11. Strachan JA, Mowat C. The use of faecal haemoglobin in<br />
deciding which patients presenting to primary care require<br />
further investigation (and how quickly) – the FIT approach.<br />
eJIFCC <strong>2021</strong>;32:52-60. https://www.ifcc.org/media/478839/<br />
ejifcc<strong>2021</strong>vol32no1pp052-060.pdf (Accessed 19 March <strong>2021</strong>).<br />
12. Zahida Z, Carolyn P, Benton SC. Does visually over-loaded<br />
HM-JACKarc collection device impact faecal haemoglobin<br />
results? Ann Clin Biochem 2020 Dec 3:4563220976749. doi:<br />
10.1177/0004563220976749. Epub ahead of print.<br />
13. Benton SC, Symonds E, Djedovic N, Jones S, Deprez L, Kocna P,<br />
Maria Auge J; International Federation of Clinical Chemistry Faecal<br />
Immunochemical Test Working Group (IFCC FIT-WG). Faecal<br />
immunochemical tests for haemoglobin: Analytical challenges<br />
and potential solutions. Clin Chim Acta <strong>2021</strong> Feb 9;517:60-5. doi:<br />
10.1016/j.cca.<strong>2021</strong>.01.024. Epub ahead of print.<br />
14. Alpha Laboratories Ltd. Bespoke patient packs help support cancer<br />
testing progress in the South West. Leading Edge. Vol. 2020, No. 1.<br />
http://files.alphalabs.co.uk/e-mags/Leading_Edge_2020_Issue_1/<br />
page_5.html (Accessed 23 March <strong>2021</strong>).<br />
8
FEATURE<br />
How can you reduce the risk to<br />
your Crohn’s disease patients<br />
of serious COVID-19 disease? 1<br />
Prescribe<br />
Entocort ® CR:<br />
classified by the<br />
BSG as lowest risk<br />
of serious COVID-19<br />
disease, compared<br />
to higher-risk<br />
prednisolone 1<br />
Entocort ® CR: BSG-recommended control patients can count on 1–3<br />
Entocort ® CR is indicated for the induction<br />
of remission in adults with mild to<br />
moderate active Crohn’s disease affecting<br />
the ileum and/or the ascending colon. 4<br />
ENTOCORT CR 3mg Capsules (budesonide) -<br />
Prescribing Information<br />
Please consult the Summary of Product Characteristics<br />
(SmPC) for full prescribing Information<br />
Presentation: Hard gelatin capsules for oral administration<br />
with an opaque, light grey body and an opaque, pink cap<br />
marked CIR 3mg in black radial print. Contains 3mg<br />
budesonide. Indications: Induction of remission in patients<br />
with mild to moderate Crohn’s disease affecting the ileum<br />
and/or the ascending colon. Induction of remission in patients<br />
with active microscopic colitis. Maintenance of remission in<br />
patients with microscopic colitis. Dosage and<br />
administration: Active Crohn’s disease (Adults): 9mg once<br />
daily in the morning for up to eight weeks. Full effect achieved<br />
in 2-4 weeks. When treatment is to be discontinued, dose<br />
should normally be reduced in final 2-4 weeks. Active<br />
microscopic colitis (Adults): 9mg once daily in the morning.<br />
Maintenance of microscopic colitis (Adults): 6mg once daily in<br />
the morning, or the lowest effective dose. Paediatric<br />
population: Not recommended. Older people: No special<br />
dose adjustment recommended. Swallow whole with water.<br />
Do not chew. Contraindications: Hypersensitivity to the<br />
active substance or any of the excipients. Warnings and<br />
Precautions: Side effects typical of corticosteroids may<br />
occur. Visual disturbances may occur. If a patient presents<br />
with symptoms such as blurred vision or other visual<br />
disturbances they should be considered for referral to an<br />
ophthalmologist for evaluation of the possible causes.<br />
Systemic effects may include glaucoma and when prescribed<br />
at high doses for prolonged periods, Cushing’s syndrome,<br />
adrenal suppression, growth retardation, decreased bone<br />
mineral density and cataract. Caution in patients with infection,<br />
hypertension, diabetes mellitus, osteoporosis, peptic ulcer,<br />
glaucoma or cataracts or with a family history of diabetes or<br />
glaucoma. Particular care in patients with existing or previous<br />
history of severe affective disorders in them or their first<br />
degree relatives. Caution when transferring from<br />
glucocorticoid of high systemic effect to Entocort CR. Chicken<br />
pox and measles may have a more serious course in patients<br />
on oral steroids. They may also suppress the HPA axis and<br />
reduce the stress response. Reduced liver function may<br />
increase systemic exposure. When treatment is discontinued,<br />
reduce dose over last 2-4 weeks. Concomitant use of CYP3A<br />
inhibitors, such as ketoconazole and cobicistat-containing<br />
products, is expected to increase the risk of systemic side<br />
effects and should be avoided unless the benefits outweigh<br />
the risks. Excessive grapefruit juice may increase systemic<br />
exposure and should be avoided. Patients with fructose<br />
intolerance, glucose-galactose malabsorption or sucroseisomaltase<br />
insufficiency should not take Entocort CR. Monitor<br />
height of children who use prolonged glucocorticoid therapy<br />
for risk of growth suppression. Interactions: Concomitant<br />
colestyramine may reduce Entocort CR uptake. Concomitant<br />
oestrogen and contraceptive steroids may increase effects.<br />
CYP3A4 inhibitors may increase systemic exposure. CYP3A4<br />
inducers may reduce systemic exposure. May cause low<br />
values in ACTH stimulation test. Fertility, pregnancy and<br />
lactation: Only to be used during pregnancy when the<br />
potential benefits to the mother outweigh the risks for the<br />
foetus. May be used during breast feeding. Adverse<br />
reactions: Common: Cushingoid features, hypokalaemia,<br />
behavioural changes such as nervousness, insomnia, mood<br />
swings and depression, palpitations, dyspepsia, skin reactions<br />
(urticaria, exanthema), muscle cramps, menstrual disorders.<br />
Uncommon: anxiety, tremor, psychomotor hyperactivity.<br />
Rare: aggression, glaucoma, cataract, blurred vision,<br />
ecchymosis. Very rare: Anaphylactic reaction, growth<br />
retardation. Prescribers should consult the summary of<br />
product characteristics in relation to other adverse reactions.<br />
Marketing Authorisation Numbers, Package<br />
Quantities and basic NHS price: PL 36633/0006. Packs of<br />
50 capsules: £37.53. Packs of 100 capsules: £75.05. Legal<br />
category: POM. Marketing Authorisation Holder: Tillotts<br />
Pharma UK Ltd, The Stables, Wellingore Hall, Wellingore,<br />
Lincoln, LN5 0HX. Date of preparation of PI: February 2020<br />
Adverse events should be reported.<br />
Reporting forms and information can be found at<br />
https://yellowcard.mhra.gov.uk. Adverse events<br />
should also be reported to Tillotts Pharma UK Ltd.<br />
Tel: 01522 813500.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
References: 1. Kennedy NA et al. Gut 2020; 0: 1–7. 2. Campieri M<br />
et al. Gut 1997; 41(2): 209–214. 3. Lamb CA et al. Gut 2019; 0: 1–106.<br />
4. Entocort ® CR 3 mg capsules – Summary of Product Characteristics.<br />
Date of preparation: July 2020. PU-00377.<br />
9
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
NHS trusts with:<br />
2WW Urgent referrals<br />
Routine referrals<br />
ADVERTORIAL FEATURE<br />
Surveillance cases<br />
Bowel cancer screening services<br />
18 WEEK SUPPORT & GASTROLEARNING:<br />
NHS Facility NHS Staff NHS<br />
processes<br />
AN UP TO DATE APPROACH TO<br />
PROVIDING UP TO DATE EDUCATION<br />
Enhanced sedation (Propofol) lists<br />
Additionally, we can support Direct Access<br />
and Rapid Access endoscopy referrals by<br />
working with the local clinical leads to agree<br />
strong governance for the management of<br />
these patients.<br />
Continuing Professional Development is an integral part of<br />
a doctors life. Continuous learning in endoscopy is equally<br />
important and furthers our technical skills, disease diagnosis and<br />
management, decision making, recognition and avoidance of<br />
complications, non-technical skills and ongoing care.<br />
Criteria & Quality<br />
We select Endoscopists with an endoscopy<br />
orientated career path and performance<br />
measures above the national average. JAG<br />
audit data is constantly monitored to ensure<br />
ongoing quality. Furthermore, we have a<br />
Quality, safety and efficiency are central to our culture in 18 Weeks Support.<br />
This is why we have partnered with GastroLearning, an endoscopic<br />
educational platform pioneered by University College London consultants.<br />
18 Week Support JAG quality standards generally exceed the UK<br />
average (National Endoscopy Database) and our complications are<br />
lower than those quoted by most studies. However our aims, through<br />
rigorous governance, webinars and GastroLearning, are to enrich<br />
education focussing on the following areas:<br />
• Technical endoscopic skills<br />
clinical governance department that is crucial<br />
• Endoscopic diagnosis (detection and characterisation)<br />
to maintaining quality and safety but also<br />
provides support to both Endoscopists and<br />
the units within which we work.<br />
• Endoscopic management of disease (guidelines and therapy)<br />
Covid has changed how professional education is delivered<br />
The Covid pandemic has acted as a catalyst for a change in the approach<br />
to providing medical education. However, changes in medical education<br />
were already happening long before it’s unwanted arrival. The current and<br />
younger generations of doctors, surgeons and allied health professionals<br />
are more than competent digital learners. Education through digital channels<br />
can be tailored by content and delivered very flexibly. “Snack” learning has<br />
become particularly popular - everything you need to know on a subject in a<br />
concise, clear format delivered by an engaging educator. <strong>Today</strong>’s generation<br />
of practitioners are now less likely to see value – or to justify - the time and<br />
expense involved in spending days in conference halls listening to lectures<br />
that may or may not be relevant to their specific need or practice. The modern<br />
approach in education is where GastroLearning excels.<br />
We provide tailored solutions to manage<br />
capacity from straight forward supply of staff<br />
to a team based managed solution to a full<br />
patient pathway including pathology review.<br />
Our commitment to improving the<br />
NHS Conference experience organisers must learn to adapt<br />
Like the NHS Trusts we work with, patient<br />
care is at the centre of everything we do. By<br />
using any spare weekend capacity within a<br />
Trust, the 18 Week Support insourcing teams<br />
are able to see a high volume of patients<br />
in a short space of time, in the familiar<br />
surrounding of the NHS Trust.<br />
Of course there is still a place for face-to-face conferences, both<br />
from an educational and social networking point of view. Conference<br />
organisers with an innovative and dynamic approach to education will<br />
likely learn from the many new digital trends that have taken centrestage<br />
in the past year. But some will not and will likely be less popular.<br />
Whilst the past year has seen a plethora of digital learning events,<br />
transplanting the traditional format of a conference online does not<br />
work. Few can sit in front of a screen for an endless stream of lectures<br />
for hours on end without interaction and there is little educational benefit<br />
in doing so. Digital education is here to stay but it must be delivered in<br />
an innovative fashion that meets the needs of the modern generation.<br />
New ways of digital learning in CPD provision<br />
An ethical company<br />
We’re an ethical and transparent company<br />
that’s financially accountable and financially<br />
through a bespoke platform on iPad and, in November 2020, we<br />
responsible. We’re committed to the NHS<br />
10<br />
and the delivery of high-quality care, and to<br />
helping Trusts reduce RTT waiting times.<br />
GastroLearning has been involved in the provision of <strong>Gastroenterology</strong><br />
education for over 10 years, most notably through running national and<br />
international conferences. But we have always recognised the need to<br />
modernise. For the past 3 years we have supplemented the traditional<br />
face-to-face conference with the delivery of interactive digital education<br />
launched our online platform which already has a global following.<br />
Clinical team<br />
All 18 Week Support Practitioners Access Free Education<br />
Our weekly “Express Packages” published every Thursday provides a<br />
selection of educational material utilising varying formats, from edited<br />
video cases and 5 minute lectures to “Top Tips” presentations and<br />
literature summaries. These Happy packages patient are aimed at covering important<br />
topics in a concise fashion while catering for differing educational needs.<br />
We also run a hugely popular 30 minute “Live Show” on the first<br />
Wednesday of every month in which an expert is interviewed on a topic<br />
relevant Who to we’re every Gastroenterologist. looking for The show is supplemented by<br />
additional educational material to maximise the learning opportunities<br />
We are interested in meeting with Consultant<br />
and key topics are accompanied with interactive quizzes to reinforce the<br />
learning.<br />
Gastroenterologists,<br />
Finally, we understand the<br />
senior<br />
importance<br />
nurses<br />
of social<br />
and<br />
media<br />
clinical<br />
and are<br />
active on Twitter (@GastroLearn) with a rapidly rising number of followers.<br />
Twitter nurse is becoming specialists an increasingly throughout popular method the for UK. individuals to<br />
access and share education. It provides the opportunity to receive “snack”<br />
learning and key messages can be shared, reaching a global platform.<br />
Our remuneration package is second to<br />
none and is per session rather than per case<br />
which allows our teams to work in a safe and<br />
calm environment’<br />
All practitioners registered with 18 Week Support are able to access all<br />
of this education content free of charge.<br />
A future of effective partnerships and even newer<br />
technology<br />
Ways in which CPD and its associated learning are delivered will<br />
continue to evolve rapidly. Although digital approaches are already<br />
the norm in many areas of medical education, there is an increasing<br />
footprint of artificial intelligence and virtual reality in our day to day lives<br />
About you<br />
which provides immensely exciting possibilities to enhance education<br />
further. GastroLearning and 18 Week Support will strive to be at the<br />
forefront If you of have this and an ensure excellent high-quality NHS education record is delivered and to all of<br />
its practitioners and to the wider gastroenterology community in the UK.<br />
want to help clear NHS waiting list<br />
backlogs, reduce RTT waiting times and<br />
provide high-quality patient care, get in<br />
If you have an excellent NHS record and want to help clear waiting<br />
touch by calling on 020 3966 9081 or email<br />
list backlogs, reduce RTT waiting times and provide high-quality<br />
recruitment@18weeksupport.com<br />
patient care, get in touch by calling on 0203 869 8790 or email us<br />
Dr David Graham and Dr Matthew Banks<br />
Join us: www.gastrolearning.com Follow us on Twitter: @Gastrolearn<br />
at Recruitment.team@18weeksupport.com<br />
Alternatively if you are procurer of 18 Week Support services,<br />
please contact busdev@18weeksupport.com<br />
18 Week Support<br />
www.18weeksupport.com<br />
Dr Matthew Banks Banks<br />
Clinical Lead for <strong>Gastroenterology</strong><br />
18 Week Support<br />
London 3rd Floor, 19-21 Great Tower Street, London EC3R 5AR<br />
Birmingham Unit 25, Lichfield Business Village, The Friary WS13 6QG<br />
GASTROENTEROLOGY TODAY - SPRING 2019
IDENTIFYING ATROPHIC<br />
GASTRITIS WITH THE AID<br />
OF GASTROPANEL ® FROM<br />
BIOHIT HEALTHCARE<br />
A first-line test to prioritise<br />
gastroscopy referrals<br />
FEATURE<br />
BIOHIT HealthCare’s GastroPanel is a simple and effective<br />
first-line test to diagnose Helicobacter pylori (H. pylori) and<br />
atrophic gastritis in patients presenting with dyspepsia and<br />
upper abdominal symptoms. Where endoscopy resources are<br />
overstretched and capacity is restricted, GastroPanel helps by<br />
identifying those at greatest risk in a primary care setting prior<br />
to referral.<br />
Chronic H. pylori infection is the primary cause of atrophic<br />
gastritis – a condition of the gastric mucosa considered to be<br />
the greatest independent risk factor for developing gastric<br />
cancer – and current guidance recommends that individuals<br />
with extensive gastric atrophy undergo regular endoscopic<br />
surveillance to closely monitor their disease progression.<br />
Early detection of those individuals with a significant risk<br />
of developing gastric cancer is the key to effective patient<br />
management, helping to reduce unnecessary referrals, and<br />
improving survival rates through earlier diagnoses.<br />
GastroPanel comprises reliable and automatable assays<br />
for four stomach-specific biomarkers, enabling thorough<br />
and objective investigation of the whole gastric mucosa, and<br />
offering clinicians more confidence in their diagnoses. The<br />
highly specific IgG antibody test for identifying H. pylori is<br />
combined with the analysis of pepsinogen I, pepsinogen II and<br />
gastrin-17 to establish the structure and function of the entire<br />
gastric mucosa. Implementing this first-line diagnostic test<br />
can help to relieve the burden on overstretched gastroscopy<br />
services, streamlining referrals for high-risk patients and<br />
effectively ruling out gastrointestinal (GI) diseases for others.<br />
This patient-friendly blood test can help transform the<br />
referral pathway for upper GI investigations by aligning clinical<br />
resources and identifying those in need of endoscopy at an<br />
early stage, making it ideal for dyspepsia diagnosis.<br />
GastroPanel is a simple, effective and low cost blood test for<br />
assessment of the structure and function of the stomach in<br />
patients with dyspepsia, helping the effective diagnosis of<br />
chronic atrophic gastritis, acid output disorders, and other<br />
diseases of the gastric mucosa resulting from a H. pylori<br />
infection. It reveals the health and status of the gastric<br />
mucosa, and provides information about the associated risks.<br />
This enables the implementation of appropriate and effective<br />
treatment plans, including eradication therapy, risk-based<br />
referral for further investigation, and antacid prescription.<br />
Key advantages of GastroPanel:<br />
• Reliable detection of healthy stomach mucosa, atrophic<br />
gastritis, acid dysregulation, and H. pylori infection<br />
• Patient and provider-friendly blood test for primary care<br />
settings<br />
• Guides patient management and referral to reduce waiting<br />
times<br />
• Helps to identify patients most at risk of gastric cancer prior<br />
to endoscopy<br />
• Fast turnaround time<br />
To find out more about how GastroPanel can help diagnose gastric cancer<br />
risk in a clinical setting, visit www.biohithealthcare.co.uk/GPblog<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
BIOHIT HealthCare Ltd<br />
Pioneer House, Pioneer Business Park, North Road,<br />
Ellesmere Port, CHESHIRE, United Kingdom CH65 1AD<br />
Tel. +44 151 550 4 550<br />
info@biohithealthcare.co.uk<br />
www.biohithealthcare.co.uk<br />
11
FEATURE<br />
DIAGNOSIS AND MANAGEMENT OF COELIAC<br />
DISEASE IN SPECIALIST PAEDIATRIC<br />
GASTROENTEROLOGY CENTRES IN THE UK<br />
By Alice Andrews, Coeliac UK<br />
Coeliac disease (CD) is a systemic autoimmune condition,<br />
characterised by enteropathy of the small intestine, triggered<br />
by dietary gluten in genetically susceptible individuals. CD<br />
is estimated to affect 1% of the UK population however, only<br />
around 30% of those with the condition have been diagnosed<br />
[1]. The clinical presentation of CD varies from intestinal and<br />
extraintestinal symptoms to asymptomatic presentations, making<br />
diagnosis challenging for healthcare professionals.<br />
Recent research published in the Journal of Pediatric <strong>Gastroenterology</strong><br />
and Nutrition has demonstrated excellent uptake of no-biopsy diagnosis<br />
guidelines, but sheds light on variations in follow up care amongst 29<br />
specialist paediatric gastroenterology centres in the UK [2].<br />
Diagnosis via the no biopsy pathway<br />
In 2012, European Society for Paediatric <strong>Gastroenterology</strong>, Hepatology and<br />
Nutrition (ESPGHAN) revised guidelines to allow some children with CD to<br />
be diagnosed without having a duodenal biopsy. Within these guidelines, a<br />
no biopsy pathway was suitable for symptomatic children who:<br />
• have IgA based anti-tissue transglutaminase antibodies (TGA-IgA)<br />
>ten times the upper limit of normal<br />
• positive anti-endomysial antibodies (EMA-IgA)<br />
• Positive HLA-DQ2/DQ8 haplotype.<br />
These guidelines have since been updated in 2020 with two notable<br />
changes. Diagnosis can now be made without the need for HLA-DQ2/<br />
DQ8 testing and secondly, a no biopsy approach can also be offered to<br />
asymptomatic children [3].<br />
NICE guidelines recommend that the need for a DEXA scan should<br />
be considered on an individual basis at annual review [5]. A minority<br />
(4/29) of centres reported that they performed routine DEXA scan post<br />
diagnosis and some centres only offered a scan if there was a risk of<br />
fractures or reported low vitamin D levels. Most children do not need to<br />
have a DEXA scan as early diagnosis and adherence to the GFD has<br />
been shown to improve bone density.<br />
Most centres (28/29) routinely measured vitamin D status but practice<br />
around supplementation varied. Most centres based their approach on<br />
vitamin D levels, but in some centres vitamin D supplements are offered<br />
to all CD patients regardless of their vitamin D status.<br />
Since 2015, NICE guidelines have recommended that patients can<br />
introduce gluten free (GF) oats to the diet at any stage [5]. GF oats add<br />
variety to the gluten free diet and are also a good source of soluble fibre<br />
but a small minority of people with CD are sensitive to GF oats. Less<br />
than a third of centres recommended that children included GF oats<br />
from diagnosis and the majority of centres waited until normalisation of<br />
TGA-IgA before introducing GF oats to the diet [2].<br />
New developments in paediatric coeliac<br />
disease management<br />
As there is limited research to inform the best management strategies,<br />
current guidance is based on expert consensus opinion. There is a<br />
need for more research in this area and an opportunity to undertake<br />
prospective research to assess different follow up strategies.<br />
An infographic summarising this publication is available at http://links.<br />
lww.com/MPG/C303.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
The survey carried out in 2019 concluded that in the UK, there was<br />
excellent uptake of the ESPGHAN 2012 diagnostic guidelines, with 76%<br />
centres (n=22) adopting the no biopsy pathway by 2013. Diagnosis<br />
should only be made by a paediatric gastroenterologist or consultant<br />
paediatrician with a special interest in CD however, at some UK centres<br />
the diagnosis is made by a general paediatrician [4] or an expert dietitian.<br />
Follow up care<br />
The research also investigated follow up care and found discrepancies<br />
across the UK [2]. Adopting a gluten free diet (GFD) is challenging<br />
for children and their families as they face several difficulties, from<br />
the increased cost of gluten free staple foods to school meals and<br />
socialising with friends, which can all affect their quality of life and<br />
adherence to the diet. For this reason, regular follow ups are important<br />
for providing support and help maintaining adherence to the GFD.<br />
References<br />
[1] West, J. et al. (2019) “Changes in Testing for and Incidence of Celiac Disease in<br />
the United Kingdom,” Epidemiology. Ovid Technologies (Wolters Kluwer Health),<br />
30(4) e23–e24. doi: 10.1097/ede.0000000000001006.<br />
[2] Paul, S. P. et al. (<strong>2021</strong>) “Celiac disease management in the United Kingdom<br />
specialist pediatric gastroenterology centers – a service survey” Journal<br />
of Pediatric <strong>Gastroenterology</strong> and Nutrition. <strong>2021</strong> Mar 17. doi: 10.1097/<br />
MPG.0000000000003126.<br />
[3] Husby, S. et al. (2019) European Society Paediatric <strong>Gastroenterology</strong>, Hepatology<br />
and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. Journal of<br />
Pediatric <strong>Gastroenterology</strong> and Nutrition. 70(1):141-156. doi: 10.1097/<br />
MPG.0000000000002497.<br />
[4] Paul S. P. et al. (2019) “HLA-DQ2/DQ8 typing for non-biopsy diagnosis of<br />
coeliac disease: is it necessary?” Arch Dis Child. 104:1119-20. doi: 10.1136/<br />
archdischild-2019-317297.<br />
[5] National Institute for Health and Care Excellence (2015). Coeliac disease:<br />
recognition, assessment and management. NICE guidelines 20. NICE, London.<br />
Available at https://www.nice.org.uk/guidance/ng20. [Accessed 27.04.<strong>2021</strong>]<br />
12
Optimising<br />
maintenance therapy<br />
for ulcerative colitis:<br />
Real<br />
choices<br />
When mesalazine doesn’t seem to be working, stepping<br />
up to immunosuppressants isn’t the only option<br />
Together we know more.<br />
Together we do more.<br />
FEATURE<br />
Real<br />
solution<br />
Salofalk Granules are easy to take, they have a<br />
pleasant vanilla flavour, and they’re a proven way to<br />
help patients get the most from their mesalazine 1-3<br />
Optimising therapy with once-daily Salofalk Granules in patients<br />
who were inadequately maintained on previous mesalazine resulted in: 2<br />
69% 45% 50%<br />
fewer<br />
days<br />
off work<br />
fewer<br />
GP visits<br />
due to UC<br />
fewer<br />
steroid<br />
courses used<br />
Mesalazine, the Dr Falk way<br />
Prescribing Information (refer to full SPC before prescribing):<br />
Salofalk gastro-resistant prolonged-release granules<br />
Presentation: Stick-formed or round, greyish white gastro-resistant<br />
prolonged-release granules in sachets containing 500mg, 1000mg,<br />
1.5g or 3g mesalazine per sachet. Indications: Treatment of acute<br />
episodes and the maintenance of remission of ulcerative colitis.<br />
Dosage: Adults: Once daily 1 sachet of 3g granules, 1 or 2 sachets of<br />
1.5g granules or 3 sachets of 1000mg or 500mg granules (equivalent<br />
to 1.5 – 3.0g mesalazine daily) preferably taken in the morning,<br />
according to individual clinical requirement. May be taken in three<br />
divided doses (1 sachet of 500mg granules three times daily or 1<br />
sachet of 1000mg granules three times daily) if more convenient.<br />
Maintenance: 0.5g mesalazine three times daily (morning, midday<br />
and evening) corresponding to a total dose of 1.5g mesalazine<br />
per day. For patients known to be at increased risk for relapse<br />
for medical reasons or due to difficulties to adhere to three daily<br />
doses, give 3.0g mesalazine as a single daily dose, preferably in the<br />
morning. Children: There is only limited documentation for an effect<br />
in children (age 6-18 years). Children 6 years of age and older: Active<br />
disease: To be determined individually, starting with 30-50mg/<br />
kg/day once daily preferably in the morning or in divided doses.<br />
Maximum dose: 75mg/kg/day. The total dose should not exceed the<br />
maximum adult dose. Maintenance treatment: To be determined<br />
individually, starting with 15-30mg/kg/day in divided doses. The<br />
total dose should not exceed the recommended adult dose. It is<br />
generally recommended that half the adult dose may be given to<br />
children up to a body weight of 40kg; and the normal adult dose to<br />
those above 40kg. Method of administration: Taken on the tongue<br />
and swallowed, without chewing, with plenty of liquid. Contraindications:<br />
Hypersensitivity to salicylates or any of the excipients.<br />
Severe impairment of renal or hepatic function. Warnings/<br />
Precautions: Blood tests and urinary status (dip sticks) should be<br />
determined prior to and during treatment. Caution is recommended<br />
in patients with impaired hepatic function. Should not be used in<br />
patients with impaired renal function. Mesalazine-induced renal<br />
toxicity should be considered if renal function deteriorates during<br />
treatment. Cases of nephrolithiasis reported; ensure good hydration.<br />
Patients with pulmonary disease, in particular asthma, should be<br />
carefully monitored. Patients with a history of adverse drug reactions<br />
to preparations containing sulphasalazine should be kept under close<br />
medical surveillance. If acute intolerance reactions e.g., abdominal<br />
cramps, acute abdominal pain, fever, severe headache and rash,<br />
occur, stop treatment immediately. Severe cutaneous adverse<br />
reactions (SCARs), including Stevens-Johnson syndrome (SJS) and<br />
toxic epidermal necrolysis (TEN), have been reported. Discontinue<br />
treatment at the first appearance of signs and symptoms of severe<br />
skin reactions, such as skin rash, mucosal lesions, or any other sign<br />
of hypersensitivity. Salofalk granules contain aspartame, a source of<br />
phenylalanine that may be harmful for patients with phenylketonuria.<br />
Salofalk granules contain sucrose: 0.02mg, 0.04mg, 0.06mg and<br />
0.12mg (500mg/1g/1.5g and 3g granules respectively). Interactions:<br />
Specific interaction studies have not been performed. Lactulose<br />
or similar preparations that lower stool pH: possible reduction of<br />
mesalazine release from granules due to decreased pH caused by<br />
bacterial metabolism of lactulose. With concomitant treatment with<br />
azathioprine, 6-mercaptopurine or thioguanine consider a possible<br />
increase in their myelosuppressive effects. There is weak evidence<br />
that mesalazine might decrease the anticoagulant effect of warfarin.<br />
Use in pregnancy and lactation: There are no adequate data. Do<br />
not use during pregnancy unless the potential benefit outweighs<br />
the possible risks. Limited experience in the lactation period. Use<br />
during breast-feeding only if the potential benefit outweighs the<br />
possible risks; if the infant develops diarrhoea, breast-feeding<br />
should be discontinued. Undesirable effects: Headache, dizziness,<br />
peri- and myocarditis, abdominal pain, diarrhoea, dyspepsia,<br />
flatulence, nausea, vomiting, aplastic anaemia, agranulocytosis,<br />
pancytopenia, neutropenia, leukopenia, thrombocytopenia,<br />
peripheral neuropathy, allergic and fibrotic lung reactions<br />
(including dyspnoea, cough, bronchospasm, alveolitis, pulmonary<br />
eosinophilia, lung infiltration, pneumonitis), acute pancreatitis,<br />
impairment of renal function including acute and chronic interstitial<br />
nephritis and renal insufficiency, nephrolithiasis, photosensitivity<br />
especially with pre-existing skin conditions, alopecia, Stevens-<br />
Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), myalgia,<br />
arthralgia, hypersensitivity reactions such as allergic exanthema,<br />
drug fever, lupus erythematosus syndrome, pancolitis, changes in<br />
hepatic function parameters, hepatitis, cholestatic hepatitis and<br />
oligospermia (reversible), asthenia, fatigue, changes in pancreatic<br />
enzymes, eosinophil count increased. Legal category: POM. Basic<br />
cost: Salofalk 500mg granules, pack size 100 sachets - £28.74;<br />
31.47€. Salofalk 1000mg granules, pack size 50 sachets – £28.74;<br />
32.87€. Salofalk 1.5g Granules, pack size 60 sachets - £48.85;<br />
51.29€. Salofalk 3g Granules pack size 60 sachets - £97.70; 104.06€<br />
(UK- NHS price; IE - PtW). Product licence number: Salofalk 500mg<br />
granules – PL08637/0007; PA573/3/1. Salofalk 1000mg granules –<br />
PL08637/0008; PA573/3/2. Salofalk 1.5g granules PL08637/0016;<br />
PA573/3/7. Salofalk 3g granules PL08637/0025; PA573/3/6. Product<br />
licence holder: Dr Falk Pharma GmbH, Leinenweberstr.5, D-79108<br />
Freiburg, Germany. Date of preparation: November 2020<br />
Further information is available on request.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Adverse events should be reported. Reporting forms and<br />
information can be found at https://yellowcard.mhra.gov.uk/<br />
(UK residents) or in Ireland at https://www.hpra.ie/homepage/<br />
about-us/report-an-issue/human-adverse-reaction-form. Adverse<br />
events should also be reported to Dr Falk Pharma UK Ltd at<br />
PV@drfalkpharma.co.uk.<br />
References:<br />
1. Salofalk Granules. Summary of Product Characteristics.<br />
2. Aldulaimi D et al. Poster DRF16/057 presented at the BSG<br />
Annual Meeting, June 2016, Liverpool UK.<br />
3. Keil R et al. Scand J Gastroenterol 2018; 21: 1-7.<br />
UC: ulcerative colitis<br />
13<br />
Date of preparation: January <strong>2021</strong> DrF 20/226
FEATURE<br />
THE INCIDENCE AND PREVALENCE OF INFLAMMATORY<br />
BOWEL DISEASE IN UK PRIMARY CARE:<br />
A RETROSPECTIVE COHORT STUDY OF THE IQVIA<br />
MEDICAL RESEARCH DATABASE<br />
Karoline Freeman 1* , Ronan Ryan 2 , Nicholas Parsons 1 , Sian Taylor‐Phillips 1 , Brian H. Willis 2 and Aileen Clarke 1<br />
Freeman et al. BMC Gastroenterol (<strong>2021</strong>) 21:139 https://doi.org/10.1186/s12876-021-01716-6<br />
Abstract<br />
Background: Our knowledge of the incidence and prevalence of<br />
inflammatory bowel disease (IBD) is uncertain. Recent studies reported<br />
an increase in prevalence. However, they excluded a high proportion<br />
of ambiguous cases from general practice. Estimates are needed to<br />
inform health care providers who plan the provision of services for IBD<br />
patients. We aimed to estimate the IBD incidence and prevalence in UK<br />
general practice.<br />
Methods: We undertook a retrospective cohort study of routine electronic<br />
health records from the IQVIA Medical Research Database covering 14<br />
million patients. Adult patients from 2006 to 2016 were included. IBD was<br />
defined as an IBD related Read code or record of IBD specific medication.<br />
Annual incidence and 12-month period prevalence were calculated.<br />
Results: The prevalence of IBD increased between 2006 and 2016 from<br />
106.2 (95% CI 105.2–107.3) to 142.1 (95% CI 140.7–143.5) IBD cases<br />
per 10,000 patients which is a 33.8% increase. Incidence varied across<br />
the years. The incidence across the full study period was 69.5 (95% CI<br />
68.6–70.4) per 100,000 person years.<br />
Conclusions: In this large study we found higher estimates of IBD<br />
incidence and prevalence than previously reported. Estimates are highly<br />
dependent on definitions of disease and previously may have been<br />
underestimated.<br />
Keywords: Inflammatory bowel disease, Primary health care,<br />
Epidemiology, Electronic health care records<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Background<br />
Inflammatory bowel disease (IBD) includes a group of related, chronic<br />
relapsing disorders. They place significant demand on healthcare<br />
resources including consultation time, testing and treatment. In order<br />
to plan healthcare resources, knowledge of the size of the problem<br />
is required. This can be inferred from the incidence and prevalence<br />
of IBD in the population. A recent systematic review published in the<br />
Lancet assessed the incidence and prevalence of IBD around the<br />
world [1]. Studies using UK data from the 1990s reported incidence<br />
rates ranging from 21 to 32.2/100,000 [2–4] and prevalence estimates<br />
ranging from 328 to 409/100,000 [2, 5–7]. The review suggested that<br />
incidence rates have stabilised in the western world, while other studies<br />
reported an ongoing increase in incidence rates [8, 9]. Two recent UK<br />
studies, that excluded a high proportion of ambiguous diagnoses from<br />
general practice, reported considerably higher prevalence estimates<br />
of 725–781/100,000 [10,11]. A third recent study reported estimates<br />
for ulcerative colitis and Crohn’s disease but excluded cases of IBD<br />
unclassified (IBDU) [12]. However, IBD cannot be classified in 20–30%<br />
of patients at first presentation and 13% remain unclassified 1 year<br />
later [13]. This may have resulted in underestimates of the true IBD<br />
prevalence in UK general practice. Our aim is to establish estimates of<br />
incidence and prevalence of IBD in adult patients in UK general practice<br />
using routine primary care electronic health records.<br />
UK primary care data, such as the IQVIA Medical Research Database<br />
(IMRD-UK) [formerly known as the Health Improvement Network (THIN)],<br />
are unique and particularly suitable for research. Over 95% of the UK<br />
population is registered with a GP [2, 14]. General practitioner (GPs)<br />
act as gatekeepers to all services and specialists in secondary care<br />
(excluding emergency care). Patients are usually only registered with one<br />
GP at any one point in time; and for each patient the registration date<br />
and the date when the patient leaves the practice is known. This provides<br />
longitudinal data with known start and end date of follow-up. The role of<br />
the GP extends to the management of chronic patients.<br />
The IMRD population is broadly representative of the UK population and<br />
prevalence of chronic diseases is comparable to national rates [15]. Findings<br />
can be generalised to the broader UK primary care population [15].<br />
Methods<br />
Data source<br />
Study data consisted of electronic health care records available in<br />
the IMRD. The IMRD consists of anonymised, longitudinal individual<br />
level patient data from more than 670 UK GP practices using the<br />
Vision practice software. In 2015 a total of over 14 million patients had<br />
contributed data to IMRD which reflects a coverage of about 6% of the<br />
UK population [16]. Data are based on patient consultation information<br />
including symptoms, diagnoses, investigations and medications recorded<br />
as clinical codes. Data were included into the study from GP practices<br />
from the date that the practice was deemed to be reporting all-cause<br />
mortality reliably compared to national statistics and from 1 year after the<br />
installation of the electronic medical record system. We applied these<br />
quality control measures to ensure data reliability and completeness.<br />
The IMRD has received Research Ethics Committee approval by the<br />
NHS South-East Multicentre Ethics Committee for research as a whole.<br />
Scientific Review Committees (SRCs) have been established to review<br />
IMRD study protocols for scientific merit and feasibility. This project was<br />
given approval by the SRC (SRC Reference Number 17THIN089) on<br />
23rd October 2017.<br />
14<br />
*<br />
Correspondence: k.freeman@warwick.ac.uk<br />
1<br />
Warwick Medical School, University of Warwick, Coventry, UK<br />
Full list of author information is available at the end of the article
FEATURE<br />
Study design and study population<br />
We undertook a retrospective cohort study of patients with data in the<br />
IMRD who were at least 18 years of age during the period 1 January<br />
2006 to 31 December 2016. The study cohort was dynamic with patients<br />
entering and exiting the study at different times. Patients entered the<br />
study 1 year after they registered with the GP practice or at age 18 years,<br />
whichever came later. Patients exited the study at the earliest of the<br />
following dates: deregistration with the practice; death; or 1 January 2017.<br />
Definition of IBD diagnosis<br />
The outcome of interest was newly diagnosed IBD. We searched the<br />
medical records of the study population for patients with a diagnosis of IBD.<br />
Those with a clinical code indicative of IBD and/or at least one prescription<br />
of an IBD specific medication in the patient record were classified as cases<br />
of IBD. The date of IBD diagnosis was taken as the first occurrence of a<br />
clinical code for IBD or first prescription of IBD specific medication in the<br />
patient record. We were interested in the broad category of inflammatory<br />
bowel disease and included clinical codes for general IBD, ulcerative colitis,<br />
Crohn’s disease, indeterminate colitis and microscopic colitis. Clinical<br />
code lists were adapted from those used in previous literature [6, 17].<br />
IBD specific medication included mesalazine, olsalazine and balsalazide.<br />
Sulfasalazine, prednisolone and budesonide preparations were considered<br />
IBD specific if rectal. Preparations of beclometasone needed to clearly<br />
specify use for the bowel to be included. Therefore, the definitions for<br />
medications were purposefully narrow and decisions on inclusion were<br />
exclusive if in doubt. The complete code list to identify IBD diagnoses is<br />
available in Additional file 1.<br />
Analysis<br />
The annual incidence and 12-month period prevalence of IBD were<br />
determined for 2006–2016 considering all adult patients contributing<br />
data to IMRD in that period. Annual incidence was defined as the<br />
number of new cases of IBD during a 1 year period over the total time<br />
each patient was observed (person-time at risk). Period prevalence was<br />
defined as new and pre-existing IBD cases during a 12-month period<br />
over the number of patients in the IMRD database during the same time<br />
period. Confidence intervals for incidence rates were exact Poisson<br />
confidence limits. Confidence intervals for prevalence were calculated<br />
using the Wilson procedure for proportions without a correction for<br />
continuity. Incidence rates for male and female patients were compared<br />
using the two sample z test.<br />
All analyses were undertaken in R version 3.6.1 (Vienna, Austria)<br />
[18]. The package “epitools” was used to calculate exact confidence<br />
intervals for incidence rates [19]. Graphs were drawn using the package<br />
“ggplot2” [20].<br />
Results<br />
IBD incidence and prevalence<br />
We retrieved 6,965,853 records of adult patients from the IMRD<br />
database and excluded 33,730 patients who entered the study after the<br />
study period (Fig. 1). We included a total of 6,932,123 patients in the<br />
analysis of IBD prevalence. The prevalence of IBD increased between<br />
2006 and 2016 from 106.2 (95% CI 105.2–107.3) to 142.1 (95% CI<br />
140.7–143.5) IBD cases per 10,000 in the adult IMRD population with<br />
an average increase of 2.96% per annum. This amounts to an increase<br />
of 33.8% from 2006 to 2016. More women than men had a recorded<br />
diagnosis of IBD (Fig. 2).<br />
We excluded 61,125 prevalent IBD cases from the dataset which<br />
resulted in a dataset of 6,870,998 patients for the analysis of IBD<br />
incidence (Fig. 1). There were 25,470 IBD incidence cases between<br />
2006 and 2016. 4736 (18.6%) had an IBD Read code only, 9632 (37.8%)<br />
had a prescription of an IBD medication only and 11,102 (43.6%) had<br />
both. Incidence of IBD in the adult IMRD population varied across<br />
the years with a maximum of 76.4 (95% CI 73.6–79.4) per 100,000<br />
recorded in 2010 and the lowest incidence of 63.5 (95% CI 60.4–66.7)<br />
per 100,000 recorded in 2016 (Fig. 3). The incidence across the full<br />
study period was 69.5 (95% CI 68.6–70.4) per 100,000 person years.<br />
The incidence rate was higher in women than men for the study period<br />
(73.09 versus 65.83, z = 8.3, p < 0.0001).<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Fig. 1 Overview of inclusion and exclusion of cases for the analyses of IBD incidence and prevalence<br />
Fig. 1 Overview of inclusion and exclusion of cases for the analyses of IBD incidence and prevalence<br />
15
FEATURE<br />
Fig. 2 12‐month period prevalence of IBD per 10,000 adult IMRD population<br />
Fig. 2 12-month period prevalence of IBD per 10,000 adult IMRD population<br />
Discussion<br />
Summary of study findings<br />
The analyses of IBD prevalence and incidence included a total of<br />
6,932,123 and 6,870,998 adult patients, respectively. The prevalence of<br />
IBD in 2016 was 142.1 (95% CI 140.7–143.5) per 10,000 adult patients.<br />
The prevalence of IBD increased between 2006 and 2016 by 33.8%.<br />
This is likely due to the fact that IBD is a chronic condition which is<br />
associated Fig. 2 with 12‐month a low mortality period prevalence rate. The of mean IBD per IBD 10,000 incidence adult IMRD for the population<br />
study period was 69.3 (95% CI 66.8–71.8) per 100,000 person years.<br />
The drop in incidence between 2010 and 2011 may be an artefact or<br />
caused by an administrative change in coding/reporting standards.<br />
Over the most recent 5-year period, the incidence of IBD was relatively<br />
stable.<br />
Study strengths and limitations<br />
The IQVIA Medical Research database is a rich source of routine<br />
electronic health care records of patients managed in primary care<br />
and is particularly useful for the study of real world problems. The<br />
study population was large and covered nearly 50% of all UK Clinical<br />
Commissioning Groups [16] meaning that findings are generalisable to<br />
UK primary care in general.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Fig. 3 Annual IBD incidence per 100,000 person‐years in the adult IMRD population<br />
Fig. 3 Annual IBD incidence per 100,000 person‐years in the adult IMRD population<br />
Fig. 3 Annual IBD incidence per 100,000 person-years in the adult IMRD population<br />
16
FEATURE<br />
The criterion “registration date plus 1 year” to assess patients’ eligibility<br />
for study inclusion avoided the systematic over-reporting of incidence<br />
rates in the first year of follow-up for newly registered patients [21]. It<br />
also prevented the double counting of prevalent cases when patients<br />
transfer from one IMRD practice to another.<br />
Limitations that might have affected the research are linked to<br />
characteristics of routine data.<br />
IBD diagnoses might be missing either due to incorrect coding,<br />
missed coding or recording as free-text. This might have led to an<br />
underestimation of IBD incidence and prevalence. However, we<br />
included a record of an IBD specific medication in the definition of an<br />
IBD diagnosis which mitigated the effect. This may explain our higher<br />
figures for IBD incidence and prevalence when compared to a recent<br />
study which only included patients with two IBD Read codes recorded<br />
or one IBD Read code and an IBD drug code [11].<br />
Potential misclassification through miscoding of ulcerative colitis as<br />
Crohn’s disease and vice versa, or by using higher order codes rather<br />
than disease specific codes was of no consequence to our study. We<br />
were interested in the broad category of inflammatory bowel disease<br />
rather than sub-category, severity or location of disease. We were<br />
able to include codes for IBD and indeterminate IBD and present the<br />
complete picture of IBD in primary care which is in contrast to a recent<br />
study which only focused on patients with a diagnosis of ulcerative<br />
colitis or Crohn’s disease [12].<br />
A limitation of our study may be our inability to verify IBD cases. While<br />
we mitigated against under-coding, over-coding is a possibility. A study<br />
reported that about 6% of IBD codes did probably not relate to a true<br />
IBD diagnosis [6]. However, the study relied on confirmatory data from<br />
GP questionnaires and considered coded data from 20 years ago.<br />
Findings in the context of existing literature<br />
Published figures on UK IBD incidence rates range from 21 to<br />
37.5/100,000 [2–4, 10–12]. Studies consistently report that prevalence<br />
is rising worldwide because of the low mortality associated with this<br />
chronic condition. UK prevalence estimates range from 328/100,000 in<br />
the 1990s [6] to 970/100,000 in 2017 [12].<br />
Our estimates of incidence and prevalence of IBD in the UK are about<br />
1.8 and 1.5 times higher than the most recent estimates. Published<br />
studies are very heterogeneous, complicating comparison of reported<br />
rates across studies. Major variations that explain at least some of the<br />
differences include: (1) our study included adult patients only, while<br />
the majority of other studies covered a wider age range including<br />
children. This impacts the incidence and prevalence rates of IBD which<br />
has an onset that peaks in adulthood. (2) Improvements in diagnostic<br />
technology now enable the detection of milder cases [9]. (3)<br />
Some smaller studies used GP records to identify cases with<br />
subsequent exclusion of unverified cases. Exclusions ranged from 8<br />
to 26% of patients [2, 3, 10]. This could have underestimated true IBD<br />
prevalence. (4) Studies used different definitions of disease. A number<br />
of studies did not include indeterminate IBD or microscopic IBD in<br />
their definition. A recent study reported the incidence and prevalence<br />
of ulcerative colitis and Crohn’s disease in the IMRD-UK database<br />
[12]. The study only included Read codes for Crohn’s disease and<br />
ulcerative colitis in the definition of disease. In contrast we used a very<br />
comprehensive and sensitive list of Read codes and drug codes (48<br />
codes) for the identification of IBD, ulcerative colitis, Crohn’s disease,<br />
indeterminate IBD and microscopic colitis. In addition, a previous study<br />
using the IMRD-UK data used a similar list of Read codes to our study<br />
for the identification of IBD. However, they included non-specific IBD<br />
medications to identify IBD cases and only included patients with at<br />
least two subsequent IBD records or an IBD record and a recorded<br />
prescription of an IBD related drug [11]. According to our data, this<br />
approach may have missed at least 37.8% of cases. We were able<br />
to increase the sensitivity of our Read code list by using medications<br />
to identify additional IBD cases because we restricted inclusion of<br />
prescriptions to IBD specific medications. This is an advantage of our<br />
study over these two recent IMRD-UK studies.<br />
Implications for research and practice<br />
Taken together, the evidence suggests that the IBD incidence and<br />
prevalence in the UK adult population may be higher than the latest<br />
published figures. Some of the differences in reported rates may be<br />
due to differences in methodology including differences in methods<br />
of case definition [22]. Case definition is complicated by the fact that<br />
IBD is a heterogeneous group of disorders. Crohn’s disease and<br />
ulcerative colitis are considered as the two extremes of a spectrum<br />
of chronic gut disorders [23]. Furthermore, the phenotype of IBD is<br />
not uniform resulting in IBD unclassified cases [13, 24]. The overlap<br />
with other infectious, inflammatory and autoimmune disorders led to<br />
suggestions to diverge from the classification of IBD into ulcerative<br />
colitis and Crohn’s disease and to reclassify IBD considering a broader<br />
disease spectrum [25]. This argues for a broader definition of IBD in the<br />
estimation of IBD incidence and prevalence.<br />
Conclusions<br />
In this large study we found higher estimates of IBD incidence and<br />
prevalence than previously reported. Estimates are highly dependent on<br />
definitions of disease and previously may have been underestimated.<br />
We believe that our sensitive approach to identifying IBD cases may<br />
be more reflective of the true burden of disease in UK general practice.<br />
Health care providers who plan services for IBD patients need to make<br />
allowances for these updated figures and should consider the definition<br />
of disease in published studies.<br />
Abbreviations<br />
IBD: Inflammatory bowel disease; IMRD: IQVIA Medical Research<br />
Database; THIN: The health improvement network; GP: General<br />
practitioner; CI: Confidence interval; IBDU: IBD unclassified.<br />
Supplementary Information<br />
The online version contains supplementary material available at https://<br />
doi.org/10.1186/ s12876-021-01716-6.<br />
Additional file 1. Complete list of clinical and drug codes for the<br />
identification of IBD diagnoses in electronic health records.<br />
Acknowledgements<br />
Not applicable<br />
Authors’ contributions<br />
KF, STP, BHW, RR and AC designed the study. RR extracted the data<br />
from IMRD and created the datasets. KF and NP carried out the<br />
analysis. KF, BHW, STP, NP and AC contributed to the interpretation of<br />
the findings. KF drafted the manuscript. All authors read and approved<br />
the final manuscript. KF takes responsibility for the integrity and<br />
accuracy of the data analysis. KF acts as guarantor. The corresponding<br />
author attests that all listed authors meet authorship criteria and that no<br />
others meeting the criteria have been omitted.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
17
FEATURE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Funding<br />
KF is funded by a National Institute for Health Research (NIHR) DRF<br />
award (DRF-2016-09-038) for this research project. AC is supported<br />
by the National Institute for Health Research (NIHR) Applied Research<br />
Collaboration (ARC) West Midlands. This report presents independent<br />
research funded by the National Institute for Health Research (NIHR).<br />
The views expressed are those of the authors and not necessarily those<br />
of the NHS, the NIHR or the Department of Health and Social Care. The<br />
funder had no role in the study design, data collection, data analysis<br />
and interpretation, writing of the report or the decision to submit for<br />
publication.<br />
Availability of data and materials<br />
The datasets generated during and/or analysed during the current study<br />
are not publicly available under the data sharing agreement with the<br />
University of Birmingham on behalf of IQVIA.<br />
Declarations<br />
Ethics approval and consent to participate<br />
Anonymised data were provided by the data provider IQVIA. Studies<br />
using IMRD have initial ethics approval from the NHS South-East<br />
Multicentre Ethics Committee, subject to prior independent scientific<br />
review. The Scientific Review Committee (IQVIA) approved the study<br />
protocol (SRC reference number 17THIN089).<br />
Consent for publication<br />
Not applicable.<br />
Competing interests<br />
The authors declare: KF is funded by the NIHR through a doctoral<br />
research fellowship. AC is supported by the NIHR ARC West Midlands<br />
initiative. STP is funded by the NIHR through a career development<br />
fellowship (NIHRCDF-2016-09-018). BHW reports grants from the<br />
Medical Research Council. RR and NP have nothing to declare.<br />
Author details<br />
1<br />
Warwick Medical School, University of Warwick, Coventry, UK.<br />
2<br />
Institute of Applied Health Research, University of Birmingham,<br />
Birmingham, UK.<br />
Received: 23 September 2020 Accepted: 10 March <strong>2021</strong><br />
Published online: 26 March <strong>2021</strong><br />
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6. Lewis JD, Brensinger C, Bilker WB, Strom BL. Validity and completeness of the<br />
General Practice Research Database for studies of inflammatory bowel disease.<br />
Pharmacoepidemiol Drug Saf. 2002;11(3):211–8. https://doi.org/10.1002/<br />
pds.698.<br />
7. Stone MA, Mayberry JF, Baker R. Prevalence and management of inflammatory<br />
bowel disease: a cross-sectional study from central England. Eur J<br />
Gastroenterol Hepatol. 2003;15(12):1275–80. https://doi.org/10.1097/01.<br />
meg.0000085500.01212.e2.<br />
8. Gunesh S, Thomas GA, Williams GT, Roberts A, Hawthorne AB. The incidence<br />
of Crohn’s disease in Cardiff over the last 75 years: an update for 1996–2005.<br />
Aliment Pharmacol Ther. 2008;27(3):211–9. https://doi.org/10.1111/j.1365-<br />
2036.2007.03576.x.<br />
9. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol<br />
EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and<br />
prevalence of the inflammatory bowel diseases with time, based on systematic<br />
review. <strong>Gastroenterology</strong>. 2012;142(1):46–54. https://doi.org/10.1053/j.<br />
gastro.2011.10.001.<br />
10. Hamilton B, Green H, Heerasing N, Hendy P, Moore L, Chanchlani N, Walker G,<br />
Bewshea C, Kennedy NA, Ahmad T, Goodhand J. Incidence and prevalence of<br />
inflammatory bowel disease in Devon, UK. Frontline Gastroenterol. 2020. https://<br />
doi.org/10.1136/flgastro-2019-101369.<br />
11. Pasvol TJ, Horsfall L, Bloom S, Segal AW, Sabin C, Field N, Rait G. Incidence<br />
and prevalence of inflammatory bowel disease in UK primary care: a populationbased<br />
cohort study. BMJ Open. 2020;10(7):e036584. https://doi.org/10.1136/<br />
bmjopen-2019-036584.<br />
12. King D, Reulen RC, Thomas T, Chandan JS, Thayakaran R, Subramanian A,<br />
Gokhale K, Bhala N, Nirantharakumar K, Adderley NJ, Trudgill N. Changing<br />
patterns in the epidemiology and outcomes of inflammatory bowel disease in the<br />
United Kingdom: 2000–2018. Aliment Pharmacol Ther. 2020;51(10):922–34.<br />
https://doi.org/10.1111/apt.15701.<br />
13. Geboes K, De Hertogh G. Indeterminate colitis. Inflamm Bowel Dis.<br />
2003;9(5):324–31. https://doi.org/10.1097/00054725-200309000-00007.<br />
14. Lis Y, Mann RD. The VAMP research multi-purpose database in the UK. J Clin<br />
Epidemiol. 1995;48(3):431–43. https://doi.org/10.1016/0895-4356(94)00137-F.<br />
15. Blak BT, Thompson M, Dattani H, Bourke A. Generalisability of the Health<br />
Improvement Network (THIN) database: demographics, chronic disease<br />
prevalence and mortality rates. Inform Prim Care. 2011;19(4):251–5. https://doi.<br />
org/10.14236/jhi.v19i4.820.<br />
16. Kontopantelis E, Stevens RJ, Helms PJ, Edwards D, Doran T, Ashcroft DM.<br />
Spatial distribution of clinical computer systems in primary care in England in<br />
2016 and implications for primary care electronic medical record databases: a<br />
cross-sectional population study. BMJ Open. 2018;8(2):e020738. https://doi.<br />
org/10.1136/bmjopen-2017-020738.<br />
17. The University of Manchester. Clinical Codes Repository. [cited 16/04/2020].<br />
https://clinicalcodes.rss.mhs.man.ac.uk/.<br />
18. R Core Team. R: a language and environment for statistical computing. R<br />
Foundation for Statistical Computing, Vienna, Austria; 2017. https://www.Rproject.org/.<br />
19. Aragon T. Epidemiology tools: basic tools for applied epidemiology; 2004 [cited<br />
08/09/2020]. https://www.rdocumentation.org/packages/epitools/versions/0.09.<br />
20. Wickham H. ggplot2: elegant graphics for data analysis. Springer, New York; 2016<br />
[cited 08/09/2020]. https://ggplot2.tidyverse.org.<br />
21. Lewis JD, Bilker WB, Weinstein RB, Strom BL. The relationship between time<br />
since registration and measured incidence rates in the General Practice Research<br />
Database. Pharmacoepidemiol Drug Saf. 2005;14(7):443–51. https://doi.<br />
org/10.1002/pds.1115.<br />
22. Burisch J, Jess T, Martinato M, Lakatos PL. The burden of inflammatory bowel<br />
disease in Europe. J Crohns Colitis. 2013;7(4):322–37. https://doi.org/10.1016/j.<br />
crohns.2013.01.010.<br />
23. Vermeire S, Van Assche G, Rutgeerts P. Classification of inflammatory bowel<br />
disease: the old and the new. Curr Opin Gastroenterol. 2012;28(4):321–6. https://<br />
doi.org/10.1097/MOG.0b013e328354be1e.<br />
24. Odze RD. A contemporary and critical appraisal of “indeterminate colitis.” Mod<br />
Pathol. 2015;28(Suppl 1):S30-46. https://doi.org/10.1038/modpathol.2014.131.<br />
25. Chang S, Shen B. Chapter 2—classification and reclassification of inflammatory<br />
bowel diseases: from clinical perspective. In: Shen B, editor. Interventional<br />
inflammatory bowel disease: endoscopic management and treatment of<br />
complications. Cambridge: Academic Press; 2018. p. 17–34.<br />
Publisher’s Note<br />
Springer Nature remains neutral with regard to jurisdictional claims in<br />
published maps and institutional affiliations.<br />
18
FEATURE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
19
CASE REPORT<br />
HEAVY METAL IN THE<br />
GASTROENTEROLOGY CLINIC<br />
Massardi C, Cooney J, Poullis A, Department of <strong>Gastroenterology</strong>, St George’s Hospital, London<br />
Case Study<br />
A 29-year-old male had attended the Emergency Department<br />
on several occasions over the previous month with worsening<br />
abdominal pain, constipation, nausea and vomiting. He had<br />
no past medical or surgical history and worked as a builder<br />
and decorator. There was no significant smoking or alcohol<br />
history and he had no known family history of gastrointestinal<br />
disease. Clinical examination was unremarkable. No cause<br />
had been found for his symptoms so he was referred to the<br />
<strong>Gastroenterology</strong> outpatient clinic.<br />
Routine blood tests showed deranged liver function tests (LFTs), with<br />
elevated bilirubin (31 umol/L) alanine transaminase (192 units/L) and<br />
gamma-glutamyl transferase (65 iU/L) Autoimmune and viral liver<br />
screens were negative. Ultrasound of the liver was normal apart from<br />
some hyperechogeneity in the liver in keeping with fatty infiltration.<br />
An abdominal radiograph was performed which found small specks<br />
of high attenuation material in the colon [Figure 1]. A porphyria<br />
screen was arranged due to the unclear aetiology of the patient’s<br />
symptoms and blood tests.<br />
The patient’s urine porphyria screen was found to be abnormal, with<br />
a porphyrin/creatinine ratio of 472 nmol/mmol creatinine, therefore<br />
further porphyria assays were requested.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
These demonstrated a porphobilinogen of 27.8 umol/L (normal<br />
limit
CASE REPORT<br />
of toxicity. Clinical manifestations of lead toxicity are varied and can<br />
be non-specific. Acute toxicity often manifests as abdominal pain,<br />
constipation, body pains, decreased libido, headaches, memory<br />
problems and irritability. Chronic exposure can produce anaemia,<br />
reduced neuro-cognitive function, nephropathy, tremor, hearing loss<br />
and hypertension 2 .<br />
In the paediatric population lead toxicity risks significant and<br />
irreversible neurodevelopmental damage and should be investigated<br />
in any child presenting with an unexplained alteration in mental<br />
state and behavioral changes in the presence of risk factors for lead<br />
exposure 3 .<br />
An elevated blood lead level reflects recent exogenous exposure as<br />
well as release of endogenous lead from bone and soft tissue stores.<br />
Toxicity is thought to develop due to lead competing with calcium in<br />
several biological processes, inhibiting enzymes, and altering the<br />
permeability of the blood brain barrier.<br />
The mainstay of management is the separation of the patient from<br />
the source of the lead exposure. In patient with very elevated lead<br />
levels (>50 mcg/dL) or symptoms of acute toxicity chelation therapy<br />
can be considered under specialist guidance 4,5 . The two most<br />
commonly used chelating agents are DMSA (2,3-dimercaptosuccinic<br />
acid) or EDTA (calcium disodium ethylenediaminetetraacetic acid).<br />
Chelation should not be undertaken unless exposure to lead has<br />
been curtailed, as in the presence of ongoing lead exposure,<br />
chelation may lead to enhanced absorption of lead and therefore<br />
worsening toxicity.<br />
Regular and long-term monitoring of lead levels is required until<br />
normal levels are achieved, as lead can be stored in bone for several<br />
decades. Patients with established sequelae of lead toxicity such as<br />
cardiovascular disease, cognitive dysfunction and renal failure are<br />
unlikely to see reversibility of their symptoms over time even with<br />
chelation therapy.<br />
Conclusion<br />
Lead toxicity is an uncommon yet important differential in patients<br />
presenting with persistent abdominal pain. Prompt diagnosis and<br />
subsequent treatment is imperative in negating the potentially long-term<br />
damaging effects of lead on multiple organ systems. In these patients,<br />
a through social history is the most crucial, but often overlooked, step in<br />
reaching the diagnosis.<br />
References<br />
1. J. Route Reigart, British Medical Journal Best Practice<br />
Guidelines; Approach to Lead Toxicity. Updated 17th April <strong>2021</strong>.<br />
https://bestpractice.bmj.com/topics/en-gb/755/diagnosisapproach#referencePop27<br />
2. National Toxicology Program. Health effects of low-level lead<br />
evaluation. Research Triangle Park, NC: US Department of Health<br />
and Human Services; 2012. http://ntp.niehs.nih.gov/pubhealth/hat/<br />
noms/lead/index.html<br />
3. D. A. Gildow, Lead Toxicity, Occupational Medicine 2004;54:76–81<br />
DOI: 10.1093/occmed/kqh019<br />
4. Lin JL, Ho HH, Yu CC. Chelation therapy for patients with<br />
elevated body lead burden and progressive renal insufficiency. A<br />
randomized, controlled trial. Ann Intern Med 1999; 130:7.<br />
5. Association of Occupational and Environmental Clinics. Medical<br />
management guidelines for lead-exposed adults. April 2007. http://<br />
www.aoec.org<br />
6. Centres for Disease Control (CDC) and Prevention. Adult blood lead<br />
epidemiology and surveillance (ABLES). http://www.cdc.gov/niosh/<br />
topics/ables/description.html<br />
Table 1: Risk Factors for Lead Exposure 1<br />
Age<br />
Pica syndrome<br />
Housing environment<br />
Occupation<br />
Recreational activities<br />
Traditional / herbal medicines<br />
Children between the ages of 9-36 months are at the most risk of ingesting lead-containing substances in<br />
their environment.<br />
Compulsive ingestion of material with no nutritional value. Most commonly seen in children and pregnant<br />
women.<br />
Older homes (built before 1970) may have lead piping or lead paint.<br />
Any job that involves handling material that may include lead, especially construction and decorating. The<br />
risk is increased if the job entails sanding down walls or removing paint which generates a fine dust of lead<br />
particles that are easily inhaled and ingested.<br />
Including painting, figurine or jewelry making and stained glass making.<br />
Any herbal remedy may contain lead. Most common sources are Ba- baw-san (traditional Chinese remedy<br />
for colic), Daw Tway (used in Thailand and Burma as a digestive aid), Greta (traditional Hispanic remedy<br />
for digestion or used during teething) and Ghasard (Indian folk medicine used as a tonic)<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
21
CASE REPORT<br />
INFLIXIMAB-INDUCED SEIZURES IN<br />
A PATIENT WITH CROHN’S DISEASE:<br />
A CASE REPORT<br />
Zhijie Lv 1 , Xiaoqi Zhang 2 and Li Wu 3*<br />
Lv et al. BMC Gastroenterol (<strong>2021</strong>) 21:193 https://doi.org/10.1186/s12876-021-01780-y<br />
Abstract<br />
Background: Infliximab-induced seizures in patients with Crohn’s<br />
disease are extremely rare and the mechanism of infliximab-induced<br />
seizures is unclear.<br />
Case presentation: A 60-year-old woman with Crohn’s disease<br />
experienced infliximab-induced seizures, diagnosed on normal<br />
magnetic resonance imaging of the brain. Moreover, the rechallenge<br />
with infliximab was positive.<br />
Conclusions: Neurological assessment and tight clinical monitoring<br />
before and during therapy with infliximab should be performed in<br />
patients with pre-existing seizure disorders.<br />
Keywords: Infliximab, Seizures, Crohn’s disease, Case report<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Background<br />
Infliximab is currently used as the first-line treatment for Crohn’s<br />
disease(CD). During the 20 years since its first approval in 1998,<br />
infliximab has revolutionized the treatment of inflammatory bowel<br />
disease(IBD). Over half a million patients have been treated with tumor<br />
necrosis factor (TNF)-α antagonists, but concerns regarding their<br />
safety have been raised worldwide [1].The most commonly reported<br />
adverse reactions to infliximab include acute or delayed hypersensitivity<br />
reactions; serious infections including reactivation of tuberculosis and<br />
hepatitis B virus; malignancy, especially lymphoma and hematologic<br />
reactions [2, 3]. However, new and rare side-effects have been<br />
increasingly reported in post-marketing reports. Here, we have reported<br />
a rare case of a patient with CD who experienced infliximab-induced<br />
seizures, diagnosed on normal magnetic resonance imaging (MRI) of<br />
the brain. Moreover, the rechallenge with infliximab was positive.<br />
Case presentation<br />
A 60-year-old female presented to our hospital with a 10-day history of<br />
small intestinal stenosis due to CD. The patient was diagnosed with CD<br />
in 2015 due to chief complaints of abdominal pain and watery diarrhea<br />
(3−4 times per day). The patient’s medical history was unremarkable.<br />
She was treated with mesalazine (3 g/day), which partially alleviated the<br />
symptoms of abdominal pain and diarrhea (2−3 times per day). Ten<br />
days before admission, she underwent colonoscopy, but it was difficult<br />
to advance the colonoscope due to secondary intestinal stenosis. Biopsy<br />
and three-dimensional computed tomography of the small intestine<br />
confirmed the diagnosis of CD. Following admission to the hospital, a<br />
series of related examinations were performed. Electrocardiography<br />
revealed a normalized rhythm. Further evaluation revealed the following:<br />
slight leukopenia (leukocytes count, 3.2 × 10 9 / L); serum albumin level,<br />
36.1 g/L (normal range,40−55 g/L); platelet count, 123 × 10 9 / L (normal<br />
range, 125−350 × 10 9 /L); serum calcium level, 2.18 mmol/L (normal<br />
range, 2.25−2.75 mmol/L); fecal calprotectin level, 827.162 µg/g<br />
(normal range 0−50 µg/g) and serum magnesium level, 0.82 mmol/L<br />
(normal range, 0.7−1 mmol/L). T cell spot test for tuberculosis (T-SPOT.<br />
TB) revealed negative findings. She also had no history of alcohol use<br />
or drug abuse. Subsequently, treatment with infliximab was initiated<br />
at a dosage of 5 mg/kg. She did not experience any side effects after<br />
the first infliximab infusion. Two weeks later, she received the second<br />
infliximab infusion (5 mg/kg), but after 5 days, she suddenly developed<br />
short episodes of impairment of consciousness at home along with<br />
limbs twitches and the extroversion of eyeball. During the episode, her<br />
tongue was bitten, and her head was hurt. The episodes lasted for<br />
approximately 3 min, and she was taken to a local hospital for treatment<br />
by her family. However, she was not treated after observation at the<br />
hospital (details unspecified). According to the schedule, the patient<br />
received the third infliximab infusion at a loading dose of 5 mg/kg. She<br />
experienced repeated episodes after 5 days of the third infusion. She was<br />
taken to the local hospital, and craniocerebral CT showed no obvious<br />
abnormalities. She was then admitted to the Department of Neurology<br />
for further evaluation. Laboratory data showed normal findings, except a<br />
high L-cholesterol level (3.35 mmol/L; normal range, 1.89−3.1 mmol/L)<br />
and low lencocyte count (2.7 × 10 9 /L; normal range, 3.5−9.5 × 10 9 /L).<br />
All physical examination findings were unremarkable. On the third day of<br />
admission, she experienced another similar seizure episode. Therefore,<br />
diazepam (5 mg) and sodium valproate(800 mg) were administered<br />
intravenously to control the seizures. No recurrence was observed after<br />
treatment during hospitalization. She underwent a brain 3.0 T magnetic<br />
resonance angiography (MRA), which showed no apparent abnormality.<br />
Video electroencephalography revealed background activity in the alpha<br />
range with an amplitude reduction but a good waveform. On both sides of<br />
the forehead and temporal area, scattered sharp waves were observed;<br />
the waves were more obvious on the right side. During the monitoring<br />
period, the patient was cooperative and did not show any behavioural<br />
22<br />
*<br />
Correspondence: wulily525@126.com<br />
3<br />
Center of Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, Zhejiang, China<br />
Full list of author information is available at the end of the article
CASE REPORT<br />
Table 1 Summary of patient characteristics, seizures, and outcome<br />
Features of<br />
seizures<br />
TNF-alpha<br />
inhibitor<br />
onset to<br />
seizures<br />
Inflammatory<br />
disorder<br />
Patients Age at<br />
presentation,<br />
gender<br />
EEG CSF Other Treatment<br />
for the<br />
seizures<br />
Seizures<br />
outcome<br />
Inflammatory<br />
disorder<br />
outcome<br />
Repeated<br />
episodes<br />
each lasting<br />
about 1 min<br />
and followed<br />
by several<br />
periods of<br />
generalized<br />
tonic clonic<br />
seizures<br />
lasting more<br />
than 6 min<br />
Mild excess<br />
slow wave<br />
activity<br />
Focal paroxysmal<br />
activity<br />
Normal MRI revealed<br />
abnormal<br />
T2 and fluidattenuated<br />
inversion<br />
recovery<br />
signal hyperintensities<br />
in a broadly<br />
symmetrical<br />
distribution<br />
affecting the<br />
cerebellar<br />
hemispheres,<br />
occipital<br />
poles, medial<br />
parietal<br />
lobes, and<br />
peripheral<br />
frontal lobes<br />
Not recorded MRI showed<br />
encephalopathy<br />
involving<br />
mainly cortical<br />
regions<br />
TNF-alpha<br />
inhibitor<br />
stopped,<br />
phenytoin<br />
5 days after<br />
the first<br />
infliximab<br />
administration<br />
TNF-alpha<br />
inhibitor<br />
stopped<br />
1 14, male Crohn’s<br />
disease<br />
Diffuse<br />
nonspecific<br />
cerebral<br />
dysfunction<br />
Not recorded MRI showed<br />
scattered T2/<br />
FLAIR signal<br />
abnormalities<br />
in the subcortical<br />
white<br />
matter predominantly<br />
in the frontal<br />
and posterior<br />
parietal lobes<br />
TNF-alpha<br />
inhibitor<br />
stopped<br />
No more<br />
seizures<br />
occurred<br />
No more<br />
seizures<br />
occurred<br />
No more<br />
seizures<br />
occurred<br />
Study author<br />
and year<br />
of publication<br />
Remission for<br />
6 months<br />
and finally<br />
relapse,<br />
culminating<br />
in colectomy<br />
and ileostomy.<br />
Zamvar,2009 [9]<br />
Not recorded Brigo,2011 [10]<br />
Not recorded Chow,2016 [12]<br />
abnormalities. The Electroencephalogram (EEG) confirmed the diagnosis<br />
of seizures and so far we highly suspected that the occurrence of the<br />
seizures may be associated with the use of infliximab. The patient<br />
Impairment of<br />
consciousness,<br />
amnesia<br />
and arrest<br />
of volitional<br />
movements,<br />
confusion<br />
and disorientation,<br />
aggressiveness<br />
2 days after<br />
the second<br />
infliximab<br />
administration<br />
2 74, male Crohn’s<br />
disease<br />
Experienced 2<br />
episodes of<br />
generalized<br />
tonic clonic<br />
seizures<br />
3 days following<br />
the<br />
second<br />
infliximab<br />
infusion<br />
3 24, female Crohn’s<br />
disease<br />
started maintenance therapy with valproic acid (500 mg/day) and was<br />
discharged after 6 days. Although there was a clear response to infliximab<br />
with a reduction of diarrhoea and abdominal pain, the infliximab treatment<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
23
CASE REPORT<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
Table 1 (continued)<br />
Study author<br />
and year<br />
of publication<br />
Inflammatory<br />
disorder<br />
outcome<br />
Seizures<br />
outcome<br />
EEG CSF Other Treatment<br />
for the<br />
seizures<br />
Features of<br />
seizures<br />
TNF-alpha<br />
inhibitor<br />
onset to<br />
seizures<br />
Inflammatory<br />
disorder<br />
Patients Age at<br />
presentation,<br />
gender<br />
Haddock,2011 [11]<br />
was ceased and no seizures occurred after discharge. Now thalidomide<br />
(25 mg/d) was used to maintain remission of CD. The patient was<br />
following up for the moment.<br />
Well controlled,<br />
and no further<br />
seizures<br />
at two year<br />
follow up.<br />
Three focal<br />
seizures post<br />
discharge<br />
TNF-alpha<br />
inhibitor<br />
stopped,<br />
benzodiazepine,<br />
phenytoin<br />
Normal MRI showed<br />
abnormal<br />
high signal in<br />
the subcortical<br />
region,<br />
bilateral<br />
occipital<br />
lobes, and<br />
on the right<br />
side with<br />
extension to<br />
involve the<br />
right temporal<br />
region<br />
Right temporal<br />
lobe dysfunction<br />
Nausea, visual<br />
disturbance,<br />
unresponsive<br />
dilated reactive<br />
pupils,<br />
bradycardic<br />
and hypertensive.<br />
13 days after<br />
the first<br />
infliximab<br />
infusion<br />
4 8, female Crohn’s<br />
disease<br />
TNF, tumor necrosis factor; EEG, electroencephalogram; CSF, cerebrospinal fluid; MRI: magnetic resonance imaging<br />
Discussion and conclusions<br />
Infliximab is a chimeric monoclonal antibody against the soluble and<br />
the membrane tumour necrosis factor (TNF)-α [4]. It is effective in<br />
inducing and maintaining remission in patients with moderate-to-severe<br />
CD refractory to conventional therapy [5]. However, administration of<br />
infliximab is associated with a well-recognized risk of infusion-related<br />
adverse events, such as infusion reactions, autoimmune disorders,<br />
malignancies, opportunistic infections, and serious infections [6]. The<br />
neurological effects of infliximab have also been reported. Headache is<br />
the most commonly reported, occurring in 12–18 % of patients studied<br />
in the clinical trial setting [7]. The other commonly reported events<br />
include peripheral neuropathy [8] and central nervous system and/<br />
or spinal cord demyelination. Most patients have good tolerance to<br />
infliximab; however, with its wide use in various autoinflammatory and<br />
immune diseases, it is expected that more adverse drug reactions will<br />
be reported in the future.<br />
A literature review revealed that infliximab-related seizures have been<br />
rarely reported (Table 1). In 2008, a 14-year-old boy with active CD<br />
experienced probable occipital lobe seizures, followed by several<br />
episodes of generalized tonic clonic seizures, 5 days after the first<br />
infliximab administration [9]. In 2011, Francesco Brigo et al. [10] reported<br />
a case of a 74-year-old man with CD who developed a sudden seizures<br />
2 days after the second infliximab administration. His medical history was<br />
notable for hepatitis C virus cirrhosis with normal liver function and for<br />
an ischemic right temporo-occipital stroke, but he did not have a history<br />
of previous seizures. Electroencephalography showed any paroxysmal<br />
activity. In 2011, Rosemary Haddock et al. [11] reported a case of<br />
posterior reversible encephalopathy syndrome in an 8-year-old girl with<br />
CD after infliximab administration and colectomy. In 2016, Chow et al. [12]<br />
reported a similar case of a 24-year-old woman who developed posterior<br />
reversible encephalopathy syndrome(PRES) after the second treatment<br />
with infliximab. Among the abovementioned, two cases occurred after the<br />
second injection of infliximab, and two occurred after the first injection of<br />
infliximab. There seemed to be no apparent consistency in the time of the<br />
occurrence of the adverse reaction and definitely none of the patients had<br />
a history of previous seizures.<br />
In our case, there was a direct correlation between seizures and<br />
infliximab administration. To the best of our knowledge, this is one of few<br />
case reports of infliximab-induced seizures. In contrast to the previous<br />
cases, our patient experienced the rechallenge events. Five days after<br />
the second infusion, the patient experienced actually a seizure, just<br />
failing to give enough attention. She again experienced seizures after<br />
the third infusion. This positive rechallenge was the strongest proof<br />
of side effects of infliximab. In the absence of infective, metabolic<br />
encephalopathy and other known etiologies, symptoms regressed<br />
quickly and completely. We also ruled out the possibility of seizures<br />
caused by other drugs because no special drugs were administered<br />
before the first three seizures except infliximab. MRA revealed no<br />
abnormalities. Based on the video electroencephalography findings,<br />
we speculated that the seizures were clearly associated with infliximabrelated<br />
neurotoxicity. In previously reported cases, Posterior Reversible<br />
Encephalopathy Syndrome (PRES) has been reported, but in our case,<br />
both clinical symptoms and neuroradiological results were incompatible<br />
with the diagnosis of PRES. Therefore, this case was different from the<br />
other previously reported cases.<br />
24
CASE REPORT<br />
The mechanism of infliximab-induced seizures is unclear. However, it<br />
may be due to the systemic pro-inflammatory effects of α-TNF agents<br />
that cause an inflammatory response in the nerves [13]. Therefore,<br />
infliximab should be cautiously administered to patients to minimize<br />
possible morbidity for patients. Medication withdrawal is the first step<br />
in managing patients with suspected drug-induced neuropathy [14],<br />
The adverse events can occur in the initial stage of infliximab treatment<br />
during induction phase. Moreover, all cases reported thus date had<br />
no history of previous seizures and no other plausible cause of the<br />
seizures. Consequently,we must underline the possibility of serious<br />
and unexpected adverse reactions to infliximab, which are rare and<br />
unpredictable. Considering the elimination half-life of infliximab (10<br />
days), we should pay particular attention to the adverse reactions after<br />
infliximab injection, especially before and after the second injection.<br />
Various neurological complications such as demyelination and<br />
peripheral neuropathy after treatment with TNF-α inhibitors have been<br />
reported [14, 15]. For patients with a history of demyelination, seizures<br />
or other serious neurological disorders, the use of TNF-α inhibitors<br />
may increase the risk of exacerbation of neurological symptoms.<br />
Neurological assessment and tight clinical monitoring before and<br />
during therapy with infliximab should be performed in patients with<br />
pre-existing seizure disorders. If absolutely necessary, prior assessment<br />
and appropriate measures should be still taken before initiating therapy.<br />
Further studies are still needed to evaluate the exact relationship<br />
between infliximab and seizures.<br />
Abbreviations<br />
CD: Crohn’s disease; IBD: inflammatory bowel disease; TNF-α: Tumor<br />
necrosis factor-alpha; MRI: Magnetic resonance imaging; MRA:<br />
Magnetic Resonance Angiography; EEG: Electroencephalogram; CT:<br />
Computed tomography; PRES: Posterior Reversible Encephalopathy<br />
Syndrome.<br />
Acknowledgements<br />
All authors thank the patient for her support.<br />
Authors’ contributions<br />
LZJ performed the literature review. ZXQ collected the clinical data. WL<br />
prepared the first version of the manuscript. All authors participated<br />
in further drafting and revision of the manuscript. All authors read and<br />
approved the final manuscript.<br />
Funding<br />
This research was funded by Health Commission of Zhejiang Province<br />
(No.2020KY201) and Zhejiang Chinese Medical University (No.KC201936).<br />
The funding bodies had no role in the design of the study and collection,<br />
analysis, and interpretation of data and in writing the manuscript.<br />
Availability of data and materials<br />
This case report contains clinical data from the electronic medical record<br />
in the Nanjing Drum Tower Hospital. The datasets used during the current<br />
study are available from the corresponding author on reasonable request.<br />
Declarations<br />
Ethics approval and consent to participate<br />
Authors’ institution does not require ethical approval for publication of<br />
a single case report. Written informed consent was obtained from the<br />
patient.<br />
Consent for publication<br />
Written informed consent was obtained from the patient for publication<br />
of this case report and the accompanying images.<br />
Competing interests<br />
The authors declare that they have no competing interests.<br />
Author details<br />
1<br />
Department of Pharmacy, Sir Run Run Shaw Hospital, School of<br />
Medicine, Zhejiang University, 3 Qingchun Road, Hangzhou 310006,<br />
Zhejiang, China. 2 Department of gastroenterology, Nanjing Drum Tower<br />
Hospital, The Affiliated Hospital of Nanjing University Medical School,<br />
321 Zhongshan Road, Nanjing 210008, Jiangsu, China. 3 Center of<br />
Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese<br />
Medical University, 54 Youdian Road, Hangzhou 310006, Zhejiang,<br />
China.<br />
Received: 30 November 2020 Accepted: 20 April <strong>2021</strong><br />
Published online: 27 April <strong>2021</strong><br />
References<br />
1. Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-alpha<br />
antagonists. Drug Saf. 2004;27(5):307–24.<br />
2. Melsheimer R, Geldhof A, Apaolaza I, Schaible T. Remicade ® (infliximab): 20<br />
years of contributions to science and medicine. Biologics. 2019;13:139 – 78.<br />
3. Aubin F, Carbonnel F, Wendling D. The complexity of adverse side-effects to<br />
biological agents. J Crohns Colitis. 2013;7(4):257–62.<br />
4. Bramuzzo M, Arrigo S, Romano C, et al. Efficacy and safety of infliximab in very<br />
early onset inflammatory bowel disease: a national comparative retrospective<br />
study. Unit Eur Gastroenterol J. 2019;7(6):759–66.<br />
5. Zaltman C, Amarante H, Brenner MM, et al. Crohn’s disease-treatment with<br />
biological medication. Rev Assoc Med Bras. 2019;65(4):554–67.<br />
6. Wang X, Cao J, Wang H. Risk factors associated with Infusion Reactions to<br />
Infliximab in Chinese Patients with Inflammatory Bowel Disease: A Large Single-<br />
Center Study. Med Sci Monit. 2019;25:2257–64.<br />
7. Gill C, Rouse S, Jacobson RD. Neurological complications of therapeutic<br />
monoclonal antibodies: trends from oncology to rheumatology. Curr Neurol<br />
Neurosci Rep. 2017;17(10):75.<br />
8. Shivaji UN, Sharratt CL, Thomas T, et al. Review article: managing the adverse<br />
events caused by anti-TNF therapy in inflammatory bowel disease. Aliment<br />
Pharmacol Ther. 2019;49(6):664–80.<br />
9. Zamvar V, Sugarman ID, Tawfik RF, Macmullen-Price J, Puntis JW. Posterior<br />
reversible encephalopathy syndrome following infliximab infusion. J Pediatr<br />
Gastroenterol Nut. 2009;48(1):102–5.<br />
10. Francesco Brigo 1, Luigi Giuseppe Bongiovanni. et al. Infliximab-related seizures:<br />
a first case study. Epileptic Disord. 2011;13(2):214–7.<br />
11. Haddock R, Garrick V, Horrocks I, Russell RK. A case of posterior reversible<br />
encephalopathy syndrome in a child with Crohn’s disease treated with infliximab. J<br />
Crohns Colitis. 2011;5(6):623–7.<br />
12. Chow S, Patnana S, Gupta NK. Posterior reversible encephalopathy syndrome in a<br />
patient with Crohn’s disease on infliximab. J Clin Gastroenterol. 2016;50(8):687.<br />
13. Tsouni P, Bill O, Truffert A, Liaudat C, Ochsner F, Steck AJ, et al. Anti-TNF alpha<br />
medications and neuropathy. J Peripher Nerv Syst. 2015;20(4):397–402.<br />
14. Stübgen JP. Tumor necrosis factor-alpha antagonists and neuropathy. Muscle<br />
Nerve. 2008;37(3):281–92.<br />
15. Deepak P, Stobaugh DJ, Sherid M, Sifuentes H, Ehrenpreis ED. Neurological<br />
events with tumour necrosis factor alpha inhibitors reported to the Food and<br />
Drug Administration A dverse Event Reporting System. Aliment Pharmacol Ther.<br />
2013;38(4):388–96.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
25
NEWS<br />
National Report shows<br />
Crohn’s and Colitis healthcare<br />
urgently needs improvement<br />
• Evidence from over 10,000 people with Crohn’s<br />
or Colitis and 72% of specialist IBD health<br />
services reveals that care across the UK is<br />
costing some patients their health and the NHS<br />
millions in unnecessary emergency treatment.<br />
• COVID-19 has made worse issues such<br />
as delays in diagnosis, long waits for<br />
investigations and surgery, and little access<br />
to much needed psychological and dietetic<br />
support.<br />
• Crohn’s & Colitis UK, the UK’s leading<br />
charity for Crohn’s and Colitis, as part of<br />
IBD UK, is calling for more resources and<br />
support for services to deliver better care<br />
for the half a million people living with this<br />
complex condition.<br />
• IBD must be recognised as an NHS priority<br />
with a clear government strategy in all four<br />
nations over the next 5 years.<br />
A new report from IBD UK – a coalition of<br />
leading health specialists in Crohn’s and<br />
Colitis care, including charities, 17 professional<br />
organisations and Royal Colleges - reveals<br />
a UK-wide picture of IBD care which was<br />
already stark prior to the COVID-19 pandemic.<br />
The ‘Crohn’s and Colitis Care in the UK: The<br />
Hidden Cost and a Vision for Change’ report 1<br />
is the most comprehensive assessment of UK<br />
care ever undertaken in the UK.<br />
Sarah Sleet, CEO at Crohn’s & Colitis UK<br />
and Chair of IBD UK summarises the current<br />
state of play: “Crohn’s and Colitis are serious<br />
conditions which aren’t taken seriously.<br />
Unacceptably high levels of emergency<br />
care and delays to diagnosis, investigations,<br />
and surgery, exacerbated by the COVID-19<br />
pandemic, are signs of services under<br />
pressure and a model of care which is not<br />
working. The report sets out a vision for<br />
change – this needs to be prioritised by<br />
governments across the UK and supported<br />
with a defined long-term strategy.”<br />
Diagnosis is taking too long<br />
The report found that it is taking too long<br />
for people with Crohn’s and Colitis to be<br />
diagnosed, delaying their treatment and<br />
support and resulting in potentially avoidable<br />
flares and emergency care. Of over 10,000<br />
people responding to the survey, a quarter<br />
(26%) waited over a year for their diagnosis,<br />
41% visited A&E at least once before<br />
diagnosis, and 12% visited three times. For<br />
everyone with Crohn’s and Colitis, almost three<br />
quarters (72%) of admissions to hospital were<br />
an emergency. This should not be the norm<br />
for people with IBD. Not only does this have a<br />
human health impact, but it is incredibly costly<br />
to the NHS as the report showed that the cost<br />
of managing someone in a flare is up to 6<br />
times higher than when they are in remission.<br />
Jacob is 19 years-old and lives with Crohn’s.<br />
“Over 1–2 years before I was diagnosed, I<br />
went to the GP several times. My diagnosis<br />
was sudden and scary. At 4am one morning, I<br />
was in terrible pain and couldn’t move an inch.<br />
I felt like something inside was going to pop,<br />
so an ambulance was called. I had a CT scan<br />
which showed that my bowel was perforated<br />
and I had contracted sepsis. I needed<br />
emergency surgery, which resulted in a stoma<br />
being formed to allow my bowel to rest... It had<br />
a big impact on my mental health.”<br />
Effects outside the gut are overlooked<br />
Once diagnosed, care for people with Crohn’s<br />
and Colitis is not proactive and is focused on<br />
medication, rather than the wider impact of<br />
the conditions. People are often left struggling<br />
with severe pain, extreme fatigue, anxiety, and<br />
problems outside the gut, with 89% of people<br />
reporting they found it hard cope with having<br />
Crohn’s or Colitis over the previous year.<br />
Moreover, only 1 in 10 people (10%) said they<br />
WHY NOT WRITE FOR US?<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
<strong>Gastroenterology</strong> <strong>Today</strong> welcomes the submission of<br />
clinical papers and case reports or news that<br />
you feel will be of interest to your colleagues.<br />
Material submitted will be seen by those working within all<br />
UK gastroenterology departments and endoscopy units.<br />
All submissions should be forwarded to info@mediapublishingcompany.com<br />
If you have any queries please contact the publisher Terry Gardner via:<br />
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26
NEWS<br />
were assessed for how they had been coping<br />
emotionally. Left unchecked and unchallenged,<br />
we risk losing the potential of more future<br />
generations of young people with IBD unable<br />
to live fulfilling, productive lives.<br />
People do not have access to a full range<br />
specialist care<br />
The report also found that people do not have<br />
access to the full range of specialist care they<br />
need. Most services are falling far short of<br />
meeting the IBD Standards 2 recommendations<br />
for crucial roles, including IBD nurse<br />
specialists, dietitians, and psychologists. Less<br />
than half (48%) of people felt their care was<br />
coordinated with other specialist services.<br />
The effects of Covid-19<br />
Covid-19 has exacerbated issues which were<br />
already stark prior to the pandemic, such as<br />
delays in diagnosis, long waits for elective<br />
care, surgery, and investigations, and little<br />
access to multi-disciplinary teams. The report<br />
shows that people with IBD cannot be left<br />
behind as services rebuild post-Covid.<br />
A vision for change<br />
This coalition of experts in IBD care, wants<br />
political decision makers across the four<br />
nations to ensure that IBD is recognised as an<br />
NHS priority with a clear government strategy<br />
over the next 5 years.<br />
In response to the findings from the report, Dr Ian<br />
Arnott, IBD Section Chair at the British Society<br />
of <strong>Gastroenterology</strong> says: “Despite fantastic<br />
work to improve IBD care over the last couple of<br />
decades, it’s clear that something fundamental<br />
needs to change to deliver care that is more<br />
personalised, preventative and proactive. It’s<br />
time that IBD was recognised as the serious<br />
condition it is, with appropriate prioritisation<br />
and support provided to enable significant<br />
improvements to be made across all services.<br />
This comes at a pivotal moment as services<br />
reconfigure in response to the COVID-19<br />
pandemic. We can and we must do more to<br />
ensure people with IBD receive safe, consistent,<br />
high-quality, personalised care whatever their<br />
age and wherever they live in the UK.”<br />
www.crohnsandcolitis.org.uk<br />
Footnotes:<br />
1. IBD UK, ‘Crohn’s and Colitis Care in the UK:<br />
The Hidden Cost and a Vision for Change’,<br />
<strong>2021</strong>.<br />
2. IBD Standards, IBD UK, 2019. <br />
Coeliac UK poll highlights<br />
concerns when eating out<br />
post lockdown<br />
• 36% of people said their biggest concern<br />
was being an inconvenience 1<br />
• Nearly half of people (48%) are worried<br />
about being ‘glutened’ when eating at family<br />
or friends 1<br />
• 60% said they were less confident –<br />
compared to before the lockdown – in<br />
finding gluten free venues 2<br />
In a recent poll by Coeliac UK, the national<br />
charity for people with coeliac disease and<br />
those who need to live without gluten, over a<br />
third (36%) of people responding, said their<br />
biggest concern when eating at a friend or<br />
family’s house post lockdown, was about<br />
being an inconvenience 1 .<br />
Nearly half (48%) were most worried about<br />
being accidentally ‘glutened’. A term used<br />
by people diagnosed with coeliac disease<br />
when they eat food that contains, or is crosscontaminated<br />
with, gluten; a protein found in<br />
wheat, barley or rye.<br />
In another poll 2 nearly 60% of people said they<br />
were less confident - compared to before the<br />
pandemic - in finding gluten free venues post<br />
lockdown.<br />
Coeliac UK, aims to #ShineALightOnCoeliac in<br />
a campaign running from 10-16 May <strong>2021</strong>. The<br />
campaign is focussing on the needs of children<br />
and young people, by providing resources, tips,<br />
recipes and advice for people when they are<br />
eating away from home, which can be shared<br />
with those catering for them, and in addition the<br />
charity has launched a fundraising challenge to<br />
raise £50,000 to support children with coeliac<br />
disease in the future.<br />
Hilary Croft, Coeliac UK CEO said: “Trusting<br />
other people to provide gluten free food can<br />
cause major feelings of anxiety and lead to<br />
people avoiding social events. The last thing<br />
anyone, let alone a young person needs now<br />
is more isolation. So we are aiming to shine a<br />
light on coeliac disease to make life better for<br />
everyone who needs to live gluten free.”<br />
Coeliac disease is not an allergy or an<br />
intolerance but an autoimmune disease where<br />
the body’s immune system damages the lining<br />
of the gut when gluten is eaten. There is no<br />
cure and no medication; the only treatment is<br />
a strict gluten free diet. People diagnosed with<br />
coeliac disease must maintain a strict gluten<br />
free diet for the rest of their lives to reduce<br />
the risk of very serious complications such<br />
as osteoporosis, infertility and although rare,<br />
small bowel cancer.<br />
“As more people venture back out to eat at<br />
their favourite restaurants, the poll results show<br />
a worrying majority who are now less confident<br />
about finding venues that offer safe gluten free<br />
food. Before the pandemic, social distancing<br />
and lockdowns there were venues across the<br />
UK, accredited by Coeliac UK, serving safe<br />
gluten free menu options. However, as we<br />
know the hospitality industry has been severely<br />
impacted by the pandemic, and we have<br />
unfortunately seen closures and suspensions<br />
of gluten free menus as the sector tried to<br />
survive and weather the storm.”<br />
“As lockdown eases, we are strongly<br />
supporting our accredited partners to help<br />
them continue to provide safe gluten free<br />
options. Over the coming weeks and months,<br />
we are preparing to shine a light on places<br />
you can visit again, confident in the knowledge<br />
of their commitment. And in the meantime,<br />
to assist the community when eating out, we<br />
have produced a handy pocket checklist of<br />
things to ask venues both before and when<br />
you visit them,” continued Ms Croft.<br />
Coeliac UK’s Gluten Free Accreditation<br />
programme provides customers with<br />
assurance that they can enjoy safe gluten free<br />
options and identify venues, which follow strict<br />
procedures in food handling and ingredient<br />
use, to ensure a safe gluten free experience.<br />
1 in 100 people in the UK is estimated to<br />
have coeliac disease but of these, only 30%<br />
are currently diagnosed, meaning there are<br />
nearly half a million people in the UK with<br />
undiagnosed coeliac disease.<br />
For more information about Coeliac UK<br />
Awareness Week and the Challenge Week,<br />
please see: www.coeliac.org.uk/shinealight<br />
#ShineALightOnCoeliac<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
27
NEWS<br />
EoS Network launches<br />
ground breaking online<br />
educational series for<br />
patients, clinicians & the<br />
general public<br />
‘An urgent need to raise awareness of this<br />
poorly understood condition’<br />
To mark National Eosinophilic Awareness<br />
Week, the charity EoS Network launched a<br />
series of publicly available webinars to shed<br />
light on Eosinophilic Gastrointestinal Disease<br />
(EGID), an underdiagnosed set of chronic<br />
conditions which affect the oesophagus and/or<br />
lower gut and creates lifelong difficulties with<br />
swallowing, eating and digestion.<br />
Eosinophilic Diseases are immune-mediated,<br />
most probably caused by food allergies or<br />
other environmental triggers which occurs<br />
in the upper gut (Eosinophilic Oesophagitis)<br />
and/or the lower gut (Eosinophilic Gastritis,<br />
Eosinophilic Gastroenteritis, Eosinophilic<br />
Colitis).<br />
In the most common of these conditions,<br />
Eosinophilic Oesophagitis (EoE) this<br />
immune response results in inflammation<br />
of the mucosa in the oesophagus which,<br />
if left untreated, can lead to oesophageal<br />
remodelling including the formation of<br />
strictures or furrows. In turn this creates<br />
difficulties with swallowing certain foods or<br />
tablets including food sticking or even food<br />
obstructions. (SEE NOTES). In the UK it is the<br />
single most common reason for emergency<br />
admission to A&E for food bolus (obstructions)<br />
removal. 1<br />
Patients with EoE report living with constant<br />
fear of choking, often avoid ‘tough’ ‘chewy’<br />
foods and are embarrassed to eat with others<br />
or in public due to coughing fits and/or<br />
retching when food sticks. They often develop<br />
avoidance tactics such as eating with lots of<br />
water or eating very slowly. As a consequence,<br />
understandably some develop anxiety around<br />
eating and socialising.<br />
Often misdiagnosed as GORD (gastrooesophageal<br />
reflux disease) 2 or heartburn,<br />
many sufferers go undiagnosed due to lack<br />
of clinical and general awareness. Research<br />
has found that the average time to receive a<br />
diagnosis is around eight years 3<br />
‘As a relatively newly recognised disease,<br />
it is extremely important that we improve<br />
eosinophilic gastrointestinal disease<br />
awareness amongst the public, patients and<br />
healthcare professionals,’ says Amanda<br />
Cordell, CEO of the EoS Network. ‘These<br />
webinars provide a valuable resource for<br />
all these groups and feedback has been<br />
extremely positive not only for patients but<br />
also Health Care Practitioners (HCPs) who are<br />
eager to learn more about this disease.’<br />
The series of webinars, which have been<br />
supported by the National Lottery Community<br />
Fund in conjunction with government Covid<br />
19 funding, are led by experts from across<br />
the field of gastroenterology, dietetics and<br />
allergy. They provide a complete overview of<br />
Eosinophilic Oesophagitis, covering topics<br />
such as the role of allergy in EoE, emergency<br />
issues, long term management and dietary<br />
solutions, along with information on paediatric<br />
care and on the more complex EGIDs. They<br />
will go live on the EoS Network website during<br />
the Awareness Week and will be available for<br />
anyone to access at www.eosnetwork.org<br />
‘Along with these webinars, we also provide<br />
educational tools, support and other resources<br />
via our educational hub,’ explains Amanda. ‘In<br />
WHY NOT WRITE FOR US?<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
<strong>Gastroenterology</strong> <strong>Today</strong> welcomes the submission of<br />
clinical papers and case reports or news that<br />
you feel will be of interest to your colleagues.<br />
Material submitted will be seen by those working within all<br />
UK gastroenterology departments and endoscopy units.<br />
All submissions should be forwarded to info@mediapublishingcompany.com<br />
If you have any queries please contact the publisher Terry Gardner via:<br />
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28
NEWS<br />
addition, we host a dedicated network section<br />
for registered healthcare professionals from<br />
around the world, allowing them to exchange<br />
advice, research and support on treating these<br />
unpleasant and life changing conditions.’<br />
‘EoE is a chronic disease that, if left untreated,<br />
can cause a severe food obstruction requiring<br />
emergency medical removal. If you are having<br />
the symptoms, we describe on our website<br />
then you should discuss them with your GP<br />
without delay.’<br />
‘In the meantime, vital research continues into<br />
the rarer, more complex lower gut eosinophilic<br />
diseases which are severely life impacting,<br />
an area where currently patients remain<br />
desperate for emerging clinical guidelines and<br />
treatments.’ 6<br />
For more information or to interview<br />
Amanda Cordell, please contact Graeme<br />
Whitcroft at Healthy PR on 07793980500 or<br />
GraemeWhitcroft@healthypr.co.uk<br />
About the EoS network charity<br />
The EoS Network works to ensure that every<br />
person with an Eosinophilic Gastrointestinal<br />
Disease receives a prompt accurate diagnosis,<br />
the right treatment for them and support<br />
to live with their condition. Its vision is for a<br />
world where everyone with an Eosinophilic<br />
Gastrointestinal Disease can eat without pain.<br />
The EoS Network provides information and<br />
support for patients and their families, a<br />
global platform for clinicians and researchers,<br />
educational resources and events and works<br />
with medical bodies, manufacturers and<br />
funders to ensure that the patient’s voice is<br />
heard.<br />
Notes on EoE<br />
EoE is clinically characterized by oesophageal<br />
dysfunction and histologically characterized by<br />
an eosinophil-rich inflammation, most probably<br />
caused by common food allergies or other<br />
environmental triggers. Often misdiagnosed as<br />
GORD, 2 adult symptoms include dysphagia,<br />
bolus obstruction and chest pain related<br />
to swallowing, heartburn and regurgitation.<br />
In children they can include reflux-related<br />
symptoms, nausea, vomiting, abdominal pain,<br />
refusal to eat or failure to grow. 2 Untreated<br />
EoE can lead to oesophageal remodelling<br />
including the formation of strictures and EoE is<br />
the cause of more than 50% of all emergency<br />
presentations for oesophageal food bolus Current clinical guidelines can be found @<br />
impactions. 1<br />
https://www.eosnetwork.org/medicalguidelines<br />
Annual incidence rates of EoE in western<br />
countries are 10 per 100,000 with prevalence References<br />
rates of 86 per 100,000. 4 However, for patients<br />
with oesophageal symptoms who undergo 1. Prevalence of eosinophilic oesophagitis in<br />
gastroscopy the prevalence is 7% whilst in<br />
adults presenting with oesophageal food<br />
patients with dysphagia and bolus obstruction, bolus obstruction. World J Gastrointest<br />
prevalence increases to 23-50%. 1 Many<br />
Pharmacol Ther 2015;6:244–247.<br />
patients have a history of atopy, particularly Heerasing N, Lee SY, Alexander S, et al<br />
asthma, allergic rhinitis and eczema. 5<br />
2. Eosinophilic esophagitis N Engl J Med.<br />
2015;373(17):1640–8. Furuta GT, Katzka<br />
EoE only received classification in the 1990s DA.<br />
and disease awareness, amongst both<br />
3. Gastrointest Pharmacol Ther 2016; 7(2):<br />
clinicians and the general public, is thought to 207-13. Ahmed M. World J<br />
be low. Currently, average time to diagnosis 4. Limketkai BN et al Gut 2019 ; 68 : 2152-<br />
is up to 8.1 years. 2 Due to the patchy nature 2160<br />
of the disease, diagnosis requires 6 biopsies 5. Aliment Pharmacol Ther 2016; 43(1): 3-15.<br />
to be taken from around the oesophagus<br />
Arias Á et al<br />
via endoscopy. Diagnosis is defined by 6. Eosinophilic gastrointestinal diseases<br />
histological presence of eosinophils ≥15hpf. below the belt https://doi.org/10.1016/j.<br />
jaci.2019.10.013 https://www.jacionline.<br />
Treatment for EoE is focused around three<br />
org/article/S0091-6749(19)31367-3/pdf<br />
areas: dietary exclusion, drugs and dilatation. Pesek RD Rothernberg ME<br />
Dietary exclusion is generally considered hard<br />
to maintain and costly. Dilatation, ScheBo_Gastro<strong>Today</strong>_Aug_2020 carried out Registered Multi-Ad_Address_Change<br />
Charity 1143267<br />
when the disease<br />
has progressed<br />
to oesophageal<br />
strictures, is an<br />
invasive procedure<br />
which manages the<br />
symptoms but not<br />
the cause of EoE<br />
and often has to be<br />
repeated.<br />
Until recently, all<br />
drug treatments<br />
were off-label and<br />
topical steroid<br />
therapy was not<br />
optimised for delivery<br />
to the oesophagus.<br />
However, NICE<br />
and the SMC have<br />
now recommended<br />
budesonide<br />
orodispersible tablet<br />
(Jorveza ®) for<br />
active EoE in adults,<br />
a treatment option<br />
designed to reach the<br />
area of inflammation<br />
in the oesophagus<br />
(final NICE guidance<br />
due 23rdJune).<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
29
COMPANY NEWS<br />
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BIOHIT’S TEST PANEL FOR STOMACH<br />
HEALTH BACKED BY FURTHER EVIDENCE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
A recent study published by the research group of Professor<br />
Francesco Di Mario at Parma University, Italy, found a strong<br />
relationship between low levels of plasma Gastrin-17 (G-17)<br />
and the manifestation of gastro-oesophageal reflux disease<br />
(GORD). 1 These results add to the weight of evidence behind<br />
GastroPanel ® , a test produced by BIOHIT Oyj, that includes<br />
G-17 as one of three biomarkers used in combination with<br />
a Helicobacter pylori IgG assay to distinguish the stomach<br />
health of patients with gastrointestinal problems.<br />
GastroPanel is designed for the first-line diagnosis of H. pylori infection<br />
and atrophic gastritis in patients with dyspepsia or GORD. It is a<br />
non-invasive blood test that offers an easy way to check the stomach<br />
mucosa and gastric acid secretion in the patient. This can lead to an<br />
informed decision of whether further examination is needed – usually by<br />
gastroscopy – and ultimately to the early discovery and intervention of<br />
gastrointestinal disorders.<br />
Current UK guidelines recommend an H. pylori stool antigen test in the<br />
care pathway of patients with gastrointestinal problems. However, this<br />
test fails to show mucosal damage due to long-term infection, including<br />
gastric atrophy (GA) or gastric intestinal metaplasia (GIM), both of which<br />
are precursors to cancer. In addition to testing for H. pylori infection,<br />
GastroPanel tests for three stomach-specific biomarkers – pepsinogen I,<br />
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alone, helping to non-invasively identify patients at risk.<br />
Graham Johnson, Managing Director of BIOHIT HealthCare Ltd,<br />
commented: “The results from this study showed that GORD patients<br />
both in primary care, and those that had been referred, had statistically<br />
significant lower levels of G-17 compared with the dyspeptic patients. 1<br />
This confirms that the G-17 biomarker is a reliable predictor of GORD,<br />
and further extends the scope of gastric diseases detectable with the<br />
GastroPanel. We hope this helps to implement the wider use of the<br />
GastroPanel, which is a proven, cost-effective strategy in screening<br />
patients at risk of gastric cancer.”<br />
For more information visit www.biohithealthcare.co.uk/gastropanel.<br />
About BIOHIT Healthcare Ltd<br />
BIOHIT Healthcare Ltd (www.biohithealthcare.co.uk) is part of the<br />
Finnish public company, BIOHIT OYJ, which specialises in the<br />
development, manufacture and marketing of products and analysis<br />
systems for the early diagnosis and prevention of gastrointestinal<br />
diseases. The company’s many unique and patented diagnostic<br />
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monitoring of gastrointestinal diseases efficient and cost effective.<br />
Non-invasive diagnostics are at the core of BIOHIT’s offering, making<br />
it the provider of choice for leading gastroenterologists and laboratory<br />
scientists worldwide.<br />
References<br />
1. Di Mario F, Crafa P, Franceschi M, et al. Low Levels of Gastrin 17 are Related<br />
with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD. JGLD<br />
[Internet]. 12Feb.<strong>2021</strong> [cited 11May<strong>2021</strong>];30(1):25-9. Available from:<br />
https://www.jgld.ro/jgld/index.php/jgld/article/view/2952<br />
30
COMPANY NEWS<br />
POINT-OF-CARE CALPROTECTIN<br />
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POSTER SUBMISSIONS<br />
If you have submitted a poster to previous BSG or<br />
ENDOLIVE events and would like it published in<br />
<strong>Gastroenterology</strong> <strong>Today</strong> please forward a PDF of your<br />
poster to the email address listed below.<br />
Material submitted will be seen by those working within all<br />
UK gastroenterology departments and endoscopy units.<br />
All submissions should be forwarded to info@mediapublishingcompany.com<br />
If you have any queries please contact the publisher Terry Gardner via:<br />
info@mediapublishingcompany.com<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2021</strong><br />
31
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