Gastrolenterology Today - Spring 2019 by Media Publishing Company

Volume 29 No. 1

Spring 2019

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Management of Upper Gastrointestinal Bleeding in Emergency Departments How can we improve Endoscopy and Colonoscopy Recovery for Patients

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CONTENTS

Gastroenterology Today What approach has 18 Week Support taken with regards to building an expert insourcing team?

EDITORS COMMENT

FEATURE Management of upper gastrointestinal bleeding in emergency departmentsMatthew’s Perspective:

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FEATURE The microbiome-gut-brain above axisthe national andstandards. its In addition, we monitor each clinician’s KPIsADVERTISING while they work with 18& WS.CIRCULATION: While the JAG data is an excellent quality indicator, we now want to go a step beyond that andMedia monitor the Non-Technical skills (NTS) of each Publishing Company implications for health and clinician disease as well. We now know that NTS plays an important role in safe and effectiveHouse, team performance. Therefore, in our Media 48 High Street quest to develop excellent teams who deliver a world-class service, we must focus on NTS’.

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EDITORS COMMENT

EDITORS COMMENT “Using stool for diagnostic tests is accepted and well understood, manipulation of the stool microbiome is a rapidly emerging area in gastroenterology.”

Stool : From diagnostic testing to microbiome manipulation Having spent much of time while working on my MD recruiting healthy subjects in South London to provide stool samples for faecal calprotectin analysis it is very satisfying to see this biomarker firmly establishing itself in clinical practice. A review of the primary care guidelines for its use in this edition of Gastroenterology Today remind us that the initial “binary” pathways were too simplistic. Although the new guidelines are less straightforward to follow they will, if followed in primary care, benefit patients and secondary care waiting times alike. Using stool for diagnostic tests is accepted and well understood, manipulation of the stool microbiome is a rapidly emerging area in gastroenterology. Probiotic use is popular with patients, however the evidence base is complex. An opinion piece in this edition should make all endoscopists at least pause for thought, could we see our bowel preparation instructions extending into the post procedure stage... Dr Andy Poullis St George’s Hospital

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Microscopic colitis

When chronic watery diarrhoea needs taming

CHRONIC WATERY DIARRHOEA? Check for microscopic colitis1

Diagnose Early with Endoscopist & Pathologist1 Often in patients >50 2

Prescribe Entocort® CR by brand – the only licensed treatment for the induction and maintenance of remission in microscopic colitis3 ENTOCORT CR 3mg Capsules (budesonide) - Prescribing Information Please consult the Summary of Product Characteristics (SmPC) for full prescribing Information Presentation: Hard gelatin capsules for oral administration with an opaque, light grey body and an opaque, pink cap marked CIR 3mg in black radial print. Contains 3mg budesonide. Indications: Induction of remission in patients with mild to moderate Crohn’s disease affecting the ileum and/or the ascending colon. Induction of remission in patients with active microscopic colitis. Maintenance of remission in patients with microscopic colitis. Dosage and administration: Active Crohn’s disease (Adults): 9mg once daily in the morning for up to eight weeks. Full effect achieved in 2-4 weeks. When treatment is to be discontinued, dose should normally be reduced in fi nal 2-4 weeks. Active microscopic colitis (Adults): 9mg once daily in the morning. Maintenance of microscopic colitis (Adults): 6mg once daily in the morning, or the lowest effective dose. Paediatric population: Not recommended. Older people: No special dose adjustment recommended. Swallow whole with water. Do not chew. Contraindications: Hypersensitivity to the active substance or any of the excipients. Warnings and Precautions: Side effects typical of corticosteroids may occur. Visual disturbances may occur. If a patient presents with symptoms such as blurred vision or other visual disturbances they should be considered for referral to an ophthalmologist for evaluation of the possible causes. Systemic effects may include glaucoma and when prescribed at high doses for prolonged periods, Cushing’s syndrome, adrenal suppression, growth retardation, decreased bone mineral density and cataract. Caution in patients with infection, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts or with a family history of diabetes or glaucoma. Particular care in patients with existing or previous history of severe affective disorders in them or their fi rst degree relatives. Caution when transferring from glucocorticoid of high systemic effect to Entocort CR. Chicken pox and measles may have a more serious course in patients on oral steroids. They may also suppress the HPA axis and reduce the stress response. Reduced liver function may increase systemic exposure. When treatment is discontinued, reduce dose over last 2-4 weeks.

Concomitant use of CYP3A inhibitors, such as ketoconazole and cobicistat-containing products, is expected to increase the risk of systemic side effects and should be avoided unless the benefits outweigh the risks. Excessive grapefruit juice may increase systemic exposure and should be avoided. Patients with fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take Entocort CR. Monitor height of children who use prolonged glucocorticoid therapy for risk of growth suppression. Interactions: Concomitant colestyramine may reduce Entocort CR uptake. Concomitant oestrogen and contraceptive steroids may increase effects. CYP3A4 inhibitors may increase systemic exposure. CYP3A4 inducers may reduce systemic exposure. May cause low values in ACTH stimulation test. Fertility, pregnancy and lactation: Only to be used during pregnancy when the potential benefits to the mother outweigh the risks for the foetus. May be used during breast feeding. Adverse reactions: Common: Cushingoid features, hypokalaemia, behavioural changes such as nervousness, insomnia, mood swings and depression, palpitations, dyspepsia, skin reactions (urticaria, exanthema), muscle cramps, menstrual disorders. Uncommon: anxiety, tremor, psychomotor hyperactivity. Rare: aggression, glaucoma, cataract, blurred vision, ecchymosis. Very rare: Anaphylactic reaction, growth retardation. Prescribers should consult the summary of product characteristics in relation to other adverse reactions. Marketing Authorisation Numbers, Package Quantities and basic NHS price: PL 36633/0006. Packs of 100 capsules: £84.15. Legal category: POM. Marketing Authorisation Holder: Tillotts Pharma UK Ltd, The Stables, Wellingore Hall, Wellingore, Lincoln, LN5 0HX. Date of preparation of PI: November 2018

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk. Adverse events should also be reported to Tillotts Pharma UK Ltd. Tel: 01522 813500.

Life feels good when microscopic colitis is under control4,5

References: 1. Ingle SB et al. World J Gastrointest Pathophysiol 2014; 5(1): 48-53. 2. Macaigne G et al. Am J Gastroenterol 2014; 109(9): 1461-1470. 3. Entocort® CR 3mg Capsules – Summary of Product Characteristics. November 2018. 4. Madisch A et al. Int J Colorectal Dis 2005; 20(4): 312-316. 5. Miehlke S et al. Gastroenterology 2008; 135: 1510-1516. Date of preparation: January 2019. PU-00231.

FEATURE

MANAGEMENT OF UPPER GASTROINTESTINAL BLEEDING IN EMERGENCY DEPARTMENTS, FROM BLEEDING SYMPTOMS TO DIAGNOSIS: A PROSPECTIVE, MULTICENTER, OBSERVATIONAL STUDY Pierre-Clément Thiebaud1,2, Youri Yordanov1,3,4, Jacques-Emmanuel Galimard5, Pierre-Alexis Raynal1,3, Sébastien Beaune2,6, Laurent Jacquin2,7, François-Xavier Ageron2,8, Dominique Pateron1,3* and the Initiatives de Recherche aux Urgences Group Reproduced with permission from the Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

Abstract Background

Results

Upper gastrointestinal bleeding (UGB) is common in emergency

In total, 110 EDs participated, including 194 patients with suspected

departments (EDs) and can be caused by many eso-gastro-duodenal

UGB (median age 66 years [Q1-Q3: 51-81]). Overall, 104 patients (54%)

lesions. Most available epidemiological data and data on the

had hematemesis and 75 (39%) melena. Endoscopy revealed lesions

management of UGB comes from specialized departments (intensive

in 121 patients, mainly gastroduodenal ulcer or ulcerations (41%) or

care units or gastroenterology departments), but little is known from the

bleeding lesions due to portal hypertension (20%). The final diagnosis

ED perspective.

of UGB was reversed by endoscopy in only 3% of cases. Overall, 67 patients (35%) had at least one severity sign. Twenty-one patients died

We aimed to determine the distribution of symptoms revealing UGB

(11%); 40 (21%) were hospitalized in intensive care units and 126 (65%)

in EDs and the hemorrhagic lesions identified by endoscopy. We

in medicine departments; 28 (14%) were outpatients. Mortality was

also describe the characteristics of patients consulting for UGB, UGB

higher among patients with clinical and biological severity signs.

management in the ED and patients outcomes. Conclusion Method

Most of the UGB cases in EDs are revealed by hematemesis. The

This was a prospective, observational, multicenter study covering 4

emergency physician diagnosis of UGB is rarely challenged by the

consecutive days in November 2013. Participating EDs were part of

endoscopic findings.

the Initiatives de Recherche aux Urgences network coordinated by the French Society of Emergency Medicine. All patients with suspected

Keywords: Gastrointestinal bleeding, Hematemesis, Melena,

UGB in these EDs were included.

Endoscopy, Emergency department

Background

GASTROENTEROLOGY TODAY - SPRING 2019

Upper gastrointestinal bleeding (UGB) is a common emergency, with

an endoscopy [10–13]. But these patients represent only a portion of

a variety of eso-gastro-duodenal symptoms as hematemesis, melena,

all those with UGB seen in emergency departments (EDs). Specifically

less often hematochezia or anemia. It can be caused by various

targeting UGB patients presenting in EDs could give us a more

potentially serious lesions, as peptic ulcers or varices [1]. UGB annual

comprehensive epidemiological description.

incidence tends to decrease, influenced by the latest therapeutical developments in the management of peptic ulcers or the prevention

Therefore, we aimed at describing the distribution of symptoms

of portal hypertension complications [2]. But it remains relatively high

revealing UGB in EDs and the hemorrhagic lesions identified

because of the widespread use of non-steroidal anti-inflammatory

by endoscopy. Our secondary objectives were to describe the

drugs (NSAIDS) and anti-thrombotic agents [3, 4]. Current cases of

epidemiological characteristics and management of patients with UGB,

UGB occur in patients older than previously described [4–6]. Several

including outcomes.

recommendations regarding UGB management have been published, including therapeutic interventions initiated by the emergency physicians. The implementation of these recommendations could affect

Methods

patients’ prognosis [2, 7, 8]. This prospective, observational, multicenter study was conducted over Very few studies have been conducted in the emergency setting

4 consecutive days in November 2013. We included the 110 EDs, 17

(hospital and pre-hospital settings) to describe UGB epidemiology and

with a prehospital medical unit, that were part of a network of clinical

management [9]. Existing epidemiological data usually concern UGB

research (Initiatives de Recherche aux Urgences [IRU]) coordinated by

in patients hospitalized in gastroenterology, intensive care units or after

the French Society of Emergency Medicine [SFMU].

* 1 3

Correspondence: Dominique.pateron@aphp.fr; dominique.pateron@sat.aphp.fr Service des Urgences - Hôpital Saint Antoine, Assistance Publique–Hôpitaux de Paris (APHP), Paris, France Sorbonne Universités, UPMC Paris Univ-06, Paris, France Full list of author information is available at the end of the article

FEATURE Table 1 General characteristics and treatments of patients presenting an upper gastrointestinal bleeding (UGB)

Age (median [Q1–Q3])a Sex (men; n, %)

Arrival at the ED n = 170

Pre-hospital management n = 24

Total n = 194

P value

66 [49–82]

71 [57.5–75.5]

66 [51–81]

0.71

88 (52)

17 (71)

105 (54)

0.085

Hematemesis

87 (51)

17 (71)

104 (54)

0.096

Melena

70 (41)

5 (21)

75 (39)

Hematochezia

6 (4)

2 (8)

8 (4)

Other

7 (4)

0 (0)

7 (4)

n = 143

n = 20

n = 163

Known cirrhosis

31 (22)

4 (20)

35 (21)

Known ulcer

33 (23)

5 (25)

38 (23)

0.78

Initial symptoms suggesting UGB, n (%)

Medical history and medication, n (%)b

Non-steroid anti-inflammatory drugs

10 (7)

2 (10)

12 (7)

0.64

Antithrombotic agents

54 (38)

8 (40)

62 (38)

Comorbidity

57 (40)

5 (25)

62 (38)

0.25

86 (51)

16 (67)

102 (53)

0.19

Exteriorized bleeding in the ED, n (%)c d

Clinical features of severity, n (%) Heart rate > 100 bpm

n = 166

n = 22

n = 188

36 (22)

12 (55)

48 (26)

0.003

Systolic arterial pressure < 90 mmHg

27 (16)

8 (36)

35 (19)

0.037

Marbling

5 (3)

3 (14)

8 (4)

0.053

Altered mental status Hemoglobin level, n (%)e

< 7 g/dL

Treatments in ED, n (%) Nasogastric tube

5 (3)

4 (18)

9 (5)

0.012

34 (20)

5 (24)

39 (21)

0.77

n = 170

n = 24

n = 194

15 (9)

4 (17)

19 (10)

0.26

Fluid administration

55 (32)

12 (50)

67 (35)

0.11

Transfusion

71 (42)

1 (4)

72 (37)

0.0002

Proton pump inhibitors

132 (78)

8 (33)

140 (72)

< 0.0001

Vasopressors

33 (19)

3 (13)

36 (19)

0.58

Catecholamines

2 (1)

2 (8)

4 (2)

0.075

Antibioticsf (excluding erythromycin)

8 (5)

—

Vitamin K antagonist reversal

18 (11)

1 (4)

19 (10)

0.048

Erythromycin

16 (9)

1 (4)

17 (9)

0.70

for 193 of 194 patients for 163 of 194 patients for 192 of 194 patients d for 188 of 194 patients e for 189 of 194 patients f for 170 of 194 patients b c

(hematemesis, melena, other), medical history (cirrhosis, ulcer and other

inclusion and data extraction. The STROBE recommendations for

comorbidities), and NSAIDS and/or antithrombotic treatment. In light

reporting of observational studies were followed [14].

of existing epidemiological data, showing an annual incidence of high digestive bleeding of 100 to 150/100,000 inhabitants [5], the number of

Patients

centres in the IRU network and the duration of the study of 4 days, we

All patients with suspected UGB, hematemesis with or without melena,

expected to include 150 to 300 cases of UGB. We estimated the prevalence

melena without hematemesis, hematochezia or other symptoms (acute

of UGB with 2013 data from the French Emergency Survey (FES) and the

anemia, hemorrhagic shock or syncope) suggestive of hemorrhage, who

National Institute of Statistics and Economic Studies (INSEE) data.

were seen in one of the participating pre-hospital or hospital EDs were included by the emergency physicians of the participating departments.

Assessment of disease severity

Exclusion criteria were patients aged less than 18 years old, refusal to

Data for the initial clinical items related to severity were collected,

participate or already included in the study once. For each patient, the

including signs related to blood loss (heart rate > 100 bpm, systolic

following data were collected: type of first contact with an emergency

blood pressure < 90 mmHg, marbling, altered mental status) and

medicine structure (hospital or pre-hospital), age, sex, first symptoms

haemoglobinemia (> 10, 7–10 and <7 g/dL hemoglobin level).

GASTROENTEROLOGY TODAY - SPRING 2019

The IRU correspondent for each ED was responsible for patients’

FEATURE

Fig. 1 Flow of patients from the first symptoms of suspected upper gastrointestinal bleeding (UGB) to endoscopy diagnosis. N = total number of patients. n1 = patients arriving to the emergency department. n2 = patients initially assessed by a pre-hospital medical team

GASTROENTEROLOGY TODAY - SPRING 2019

Management and treatment The following therapeutic measures, done in the ED, were collected:

Categorical variables are expressed as number and percentage. They

placement of a nasogastric tube; fluid administration; transfusion; and

were compared using Fisherâ&#x20AC;&#x2122;s exact test. Statistical analyses were

use of proton pump inhibitors, vasopressors (somatostatin, octreotide,

two-tailed, and a p value less than 0.05 was considered significant.

terlipressin), catecholamines (adrenaline, norepinephrine), anticoagulation

Analyses were performed using R statistical software, version 3.1.3

reversal and antibiotics. The use of erythromycin before endoscopy was

(www.r-project.org).

also noted. Endoscopy data concerning bleeding lesions and hemostasis procedures were noted, as were the performance of any imaging test

Ethics

(ultrasonography, CT). Patients outcome (hospitalised or outpatient), final

The study was approved by the institutional review board (IRB) (ComitĂŠ

diagnosis and hospital deaths were also collected.

de protection des personnes, Ile de France XI, Paris, France) and the Advisory Committee on Information Processing in Material Research in

Statistical analysis

the Field of Health (CCTIRS). Patients, or their next of kin, were informed

Continuous variables are presented as median, first and third quartile

that a study was being led and that their data might be used. They

(Q1-Q3) and were compared using the Wilcoxon rank sum test.

could refuse being included.

FEATURE Results

Table 2 Final diagnosis Final diagnosis

n (%)

Ulcers

44 (30)

Gastritis

16 (11)

not included in the study. The participating EDs received 46.190 visits

Variceal bleeding

30 (20)

during the study period and UGB was suspected in 0.42% of the

Esophagitis

12 (8)

situations. Thus, the estimated incidence of UGB in France, in 2013,

Mallory-Weiss tear

7 (5)

Cancer

12 (8)

Lower gastrointestinal bleeding

5 (3)

None

22 (15)a

Lower gastrointestinal bleeding

4 (9)

None

42 (91)b

During the study, we have included 194 patients with suspected UGB, No patients declined participation, no patients were excluded due to multiple inclusions, and two patients younger than 18 years old were

Endoscopy performed, n = 148 (76%)

was 122/100,000 inhabitants. Out of the 194 included patients, 24 received initial prehospital medical care (12%), median age was 66 years [Q1-Q3 51-81] and 105 (54%) were male. Overall, 104 (54%) had hematemesis and 75 melena (39%). For 15 patients (8%), the suspicion was based on other symptoms (Table 1). Bleeding externalization was observed during the ED stay of a 102 patients (53%). The flow from first

No endoscopy performed, n = 46 (24%)

symptoms to endoscopy diagnosis is reported in Fig. 1. In total, 148

patients (76%) underwent endoscopy during their hospital stay, out of

5 outpatients included 23 outpatients included

which 44 (23%) during the ED stay: 9/44 (20%) received erythromycin and 12/44 (27%) a hemostatic procedure. Endoscopy confirmed the diagnosis and revealed lesion explaining UGB in 121/148 patients (82%) (Table 2). Gastroduodenal ulcer (44/148 patients, 30%) was the most frequent lesion followed by variceal bleeding (30/148, 20%) and gastritis (16/148, 11%). In 22/148 patients (15%), no lesion was found. In 5/148 (3%) the diagnosis of UGB was overturned, with lower gastrointestinal

than one third of patients had at least one severity sign; about 20% had hypotension, < 7 g/dL hemoglobin level, and a known cirrhosis. In all, 11% of patients died; initial hypotension, marbling or altered mental status were significantly linked to mortality.

bleeding finally diagnosed.

Our proportion of patients presenting with hematemesis (54%) is close

Overall, 67/194 patients (35%) had at least one severity sign: 48 (26%)

departments, intensive care units or by emergency endoscopy [3, 9, 17,

tachycardia, 35 (19%) hypotension, some could present several severity sign (Table 1). Thirty-nine patients (21%) had a hemoglobin level < 7 g/

to literature data (42â&#x20AC;&#x201C;61%) for UGB managed in gastroenterology 18]. In a study of 1140 emergency and ambulatory care patients with UGB of ulcerative origin, the proportion of melena was higher than in

dL and 72 (37%) underwent transfusion. Data regarding type of UGB

our study (52 vs 39%), with 40% of patients having hematemesis and

management are presented in Table 1. Thirty-five patients (21%) had

8% anemia without exteriorized bleeding [19]. In our study, bleeding

a known cirrhosis. Clinical characteristics and outcomes depending

lesions were diagnosed by endoscopy in 80% of cases. One quarter

on presence or not of cirrhosis are presented in Table 3. Patients with

of patients had no endoscopy during hospitalization, often because of

a history of cirrhosis were more often younger and males than those

the low severity among outpatients and more rarely (4 cases) because

without cirrhosis. They presented with a significantly higher proportion

the patient died before endoscopy could be performed. This might

of severity signs, as heart rate > 100 bpm (p = 0.006), marbling (p =

have an impact on the distribution of the causes of UGB. In about 15%

0.031) or an altered mental status (p = 0.015). A total of 21 patients

of patients, endoscopic diagnosis was missing, which is comparable

(11%) died, of which 3 during the pre-hospital phase; 40 (21%) were

to previously published studies [5, 20, 21]. The prevalence of 41%

hospitalized in intensive care units, 126 (65%) in medicine departments

of lesions with an ulcerative origin (ulcer disease or complicated

and 28 (14%) were outpatients.

ulcerations) is close to data (28-67%) from studies including UGB cases from endoscopy examination [5, 21]. The 20% of bleeding lesions due to portal hypertension was associated to the high prevalence of

with marbling (p = 0.042) or altered mental status (p = 0.0008).

cirrhosis in our population [22]. More than a quarter of patients with

Exteriorized bleeding in the ED was also associated to a higher

cirrhosis presented bleeding from other causes than cirrhosis. This

mortality rate (p = 0.035). Deceased patients received more frequently

can be a strong argument in favor of the use of proton pump inhibitors

vasopressors (p = 0.0009) or catecholamines (p = 0.004). Although not

before endoscopy in this subset of patients, as itâ&#x20AC;&#x2122;s recommended [7],.

significant, there seem to be a trend between mortality and cirrhosis (p

In our study, the diagnosis of UGB in the ED was rarely challenged by

= 0.071) and transfusion (p = 0.057) (Table 4).

subsequent explorations (3% of cases).

Discussion

The UGB incidence estimated from our study favours the completeness of data for our included patients. Epidemiological reviews show an annual incidence of UGB of 50 to 150/100,000 inhabitants [5] and

The distribution of symptoms for suspected UGB is poorly known,

the main French study showed an annual incidence of 146/100,000

especially in EDs, even though most cases of UGB (80â&#x20AC;&#x201C;90%) are

[1]. The median age of UGB and proportion of patients older than 80

managed in EDs [11, 15, 16]. Our multicentric, prospective study

years is similar to that observed in the most recent studies and seems

performed over a short period (4 days) in French EDs found that

higher than that observed 10 years ago, with a significant proportion

for more than half of the patients (54%), the UGB was revealed by

of patients on anti-thrombotic therapy [3, 4]. The proportion of patients

hematemesis. Endoscopy revealed a lesion in about 80% of patients.

with UGB who were older than 75 years was 27% in 1996 [23] but 37%

The final diagnosis of UGB was reversed for only 3% of patients. More

in our study.

GASTROENTEROLOGY TODAY - SPRING 2019

Mortality was significantly higher for hypotensive patients (p = 0.004),

FEATURE Table 3 Patients characteristics depending on their cirrhosis history

Age (median [Q1–Q3]) Sex (men; n, %) Initial symptoms suggesting UGB, n (%)

With cirrhosis n = 35

Without cirrhosis n = 128

P value

56 [50–67.5]

73 [56–83]

0.0006

26 (74%)

69 (54%)

0.034

Hematemesis

24 (69)

60 (47)

0.005

Melena

7 (20)

60 (47)

Hematochezia

1 (3)

6 (5)

Other

2 (2)

3 (9)

21 (62)

69 (54)

Exteriorized bleeding in the ED, n (%)a b

Clinical features of severity, n (%)

0.56

n = 32

n = 127

Heart rate > 100 bpm

17 (53)

26 (20)

0.0006

Systolic arterial pressure < 90 mmHg

9 (28)

22 (17)

0.21

Marbling

4 (13)

3 (2)

0.031

Altered mental status Hemoglobin level, n (%)b

< 7 g/dL c

Upper endoscopy in ED, n (%) Hemostatic procedured Treatments in ED, n (%)

4 (13)

2 (2)

0.015

10 (29)

26 (21)

0.35

29 (26)

9 (29)

0.82

5 (17)

5 (5)

0.036

n = 35

n = 128

Nasogastric tube

5 (14)

12 (9)

0.37

Fluid administration

20 (57)

38 (30)

0.005

Transfusion

16 (46)

50 (39)

0.56

Proton pump inhibitors

28 (80)

93 (73)

0.51

Vasopressors

23 (66)

10 (8)

<0.0001

Catecholamines

2 (6)

1 (1)

0.12

Antibioticsc (excluding erythromycin)

4 (13)

2 (2)

0.020

Vitamin K antagonist reversal

19 (15)

0.027

Erythromycin

6 (17)

9 (7)

0.09 <0.0001

Final diagnosis (hospitalized patients), n (%)

Ulcer

2 (6)

38 (37)

Gastritis

3 (9)

12 (12)

Variceal bleeding

25 (74)

1 (1)

Esophagitis

2 (6)

9 (9)

Mallory-Weiss tear

6 (6)

Cancer

12 (12)

Lower GI bleeding

6 (6)

None

2 (6)

19 (18)

GASTROENTEROLOGY TODAY - SPRING 2019

for 161 of 163 patients for 159 of 163 patients for 143 of 163 patients d for 141 of 163 patients e for 137 of 163 patients b c

Two studies [4, 6] confirmed an increase in the ageing of the population

bleeding, including those with a history of cirrhosis that appeared more

with UGB, with average age 57, 59, 63 and 66 years in 1986-1987, 1995,

severe, and critically ill patients that were initially managed in the pre-

2000-2001, and 2005, respectively. As in our study, the literature shows

hospital setting. The main factors associated with mortality found in the

a male predominance, with a sex ratio between 1.3 and 2 [1, 20, 23],

literature are ageing, co-morbidities (including cirrhosis), signs of severity,

but the proportion of women with UGB is increasing [24].

an initial low blood pressure, hematemesis and low hemoglobin level [4, 5, 20, 21]. We found a significant association between mortality and

The observed severity of disease in our patients was similar to

signs of severity (low blood pressure, marbling, altered mental status),

epidemiological studies, finding mortality between 3 and 14% [4, 5, 17,

exteriorized bleeding in the ED or therapeutical interventions as the use of

21]. Our level of mortality (11%) might seem relatively high for patients with

catecholamines or vasoactive agents. There appear to be a trend toward

UGB in EDs [5], possibly because we included all patients with suspected

an association with history of cirrhosis and need to transfusion, although

FEATURE Table 4 Patients characteristics depending on their survival status Age (median [Q1–Q3])

Sex (men; n, %)

Survivors n = 172a

Dead n = 21a

P value

66.5 [49–81]

66 [57–83]

0.46

91 (53)

13 (62)

0.49

Hematemesis

90 (52)

13 (62)

0.87

Melena

67 (39)

8 (38)

Hematochezia

8 (5)

0 (0)

Other

7 (4)

0 (0)

n = 144

n = 18

Known cirrhosis

28 (19)

7 (39)

Known ulcer

35 (24)

3 (17)

0.57

Non-steroid anti-inflammatory drugs

54 (38)

8 (44)

0.61

Antithrombotic agents

58 (40)

4 (22)

0.20

Initial symptoms suggesting UGB, n (%)

Medical history and medication, n (%)c

Comorbidity

0.071

12 (8)

0 (0)

0.36

Exteriorized bleeding in the ED, n (%)d

85 (50)

16 (76)

0.035

Clinical features of severity, n (%)e

n = 167

n = 20

Heart rate > 100 bpm

39 (23)

8 (40)

0.11

Systolic arterial pressure < 90 mmHg

26 (16)

9 (45)

0.004

Marbling

5 (3)

3 (15)

0.042

Altered mental status

4 (2)

5 (25)

0.0008

34 (20)

5 (24)

0.55

39 (25)

5 (31)

0.57

11 (7)

1 (7)

1.00

n = 172

n = 21

18 (10)

1 (5)

0.70

Fluid administration

58 (34)

8 (38)

0.81

Transfusion

60 (35)

12 (57)

0.057

Proton pump inhibitors

125 (73)

14 (67)

0.61

Vasopressors

25 (15)

10 (48)

0.0009

Hemoglobin level n (%)f Upper endoscopy in ED, n (%)

< 7 g/dL g

Hemostatic procedureh Treatments in ED, n (%) Nasogastric tube

1 (1)

3 (14)

0.004

7 (5)

1 (6)

0.56

Vitamin K antagonist reversal

16 (9)

3 (14)

0.44

Erythromycin

15 (9)

2 (10)

1.00

Ulcer

41 (29)

3 (19)

0.31

Gastritis

15 (11)

1 (6)

Variceal bleeding

23 (17)

7 (44)

Esophagitis

12 (9)

0 (0)

Mallory-Weiss tear

7 (5)

0 (0)

Cancer

10 (7)

2 (13)

Lower GI bleeding

8 (6)

1 (6)

None

23 (17)

2 (13)

Final diagnosis, n (%) (hospitalized patients)

1 missing data b for 192 of 193 patients c for 162 of 193 patients d for 191 of 193 patients e for 187 of 193 patients f for 188 of 193 patients g for 169 of 193 patients h for 167 of 193 patients i for 155 of 193 patients

not significant, which could be due to a lack of statistical power of our

for these patients with a bleeding ulcer [21]. Use of anti-thrombotic agents,

study. When looking at published literature, mortality was higher in patient

a known risk factor of digestive hemorrhage [21], was frequent in our

with a history of cirrhosis [10, 23], with variceal bleeding [17, 20] but also

population but did not predict mortality.

GASTROENTEROLOGY TODAY - SPRING 2019

Catecholamines Antibioticsg (excluding erythromycin)

FEATURE Management of UGB in our cohort of patients shows an evolution of

Acknowledgments

practices, possibly influenced by recommendations [2, 7, 8]. Proton

The authors thank Laura Smales (BioMedEditing) for editing and all

pump inhibitors were used for three-quarters of our patients, and their

the members of the Initiatives de Recherche aux Urgences network

administration is now recommended as soon as possible without

(Additional file 1).

waiting for endoscopy [7]. Most patients with cirrhosis received vasopressor treatment in the first 24 h [2]. The number of transfusions

Funding

suggests that the policy of restricting transfusion is not yet followed [25].

This study did not receive any specific funding.

Only a few patients received nasogastric tubes (10%). Several studies indicated that nasogastric tube placement does not confirm the upper

Availability of data and materials

origin of a gastrointestinal bleeding [26, 27] and recommendations

Datasets are available upon request to the corresponding author.

remain unclear on this topic. Erythromycin perfusion before endoscopy is rarely used [28]. This practice, although validated by several

Authors’ contributions

studies, is not shared by some international recommendations [21].

PCT and DP designed the study. PCT acquired the data. PCT, DP, PAR,

The use of antibiotics in patients with cirrhosis remains low despite

YY drafted the paper. JEG performed the statistical analysis. All authors

recommendations on this topic [29]. Outpatient care concerned only

revised and reviewed the final paper. All authors read and approved the

14% of our patients, which is less than in studies using a severity score

final manuscript.

[30]. The use of these scores would probably increase the proportion of outpatients.

Ethics approval and consent to participate The study was approved by the institutional review board (IRB) (Comité de protection des personnes, Ile de France XI, Paris, France) and the

Limitations One main limitation of our study is the risk of selection. The departments participating in the study are a subset of the 600 French EDs, that are particularly interested in clinical research. Patients presenting at these EDs might not be representative of the general population. The IRU includes community and university hospitals, so this risk was deemed acceptable. Another limitation can be due to the short inclusion period of 4 days that might not perfectly reflect the distribution of the causes of upper GI bleeding. There’s also a possibility of under or overestimation

Advisory Committee on Information Processing in Material Research in the Field of Health (CCTIRS). Patients, or their next of kin, were informed that a study was being led and that their data might be used. They could refuse being included. Consent for publication Not applicable. Competing interests The authors declare no conflict of interest.

of UGB incidence, due possible natural variations in the number of patients presenting with UGB in EDs. The third limitation is the absence of precise quantitative data. Each local investigator, when including patients, had to choose between various categories (e.g., tachycardia >100 bpm, hemoglobin level > 10, 7–10 and <7 g/dL) to simplify data extraction sheets and ensure data quality and comprehensiveness, at the expense of severity score precision. The number of inclusions (194 patients) limits the statistical power of the study, especially for prognostic factors. Moreover, the number of deceased patients did not allow us to perform a robust multivariate analysis.

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1

Service des Urgences - Hôpital Saint Antoine, Assistance Publique–

Hôpitaux de Paris (APHP), Paris, France. 2Initiatives de Recherche aux Urgences, SFMU, French Society of of Emergency Medicine, Paris, France. 3Sorbonne Universités, UPMC Paris Univ-06, Paris,

GASTROENTEROLOGY TODAY - SPRING 2019

Conclusions

France. 4INSERM, U1153, Paris, France. 5INSERM U1153, Statistic and Epidemiologic Research Center Sorbonne Paris Cité (CRESS), ECSTRA Team, Saint-Louis Hospital, Paris, France. 6Emergency

Most of the UGB cases in EDs are revealed by hematemesis. The

department, CHU Ambroise Paré, Assistance Publique Hôpitaux de

emergency physician diagnosis of UGB is rarely challenged by the

Paris, Boulogne-Billancourt, France. 7Emergency department, Hôpital

endoscopic findings. Epidemiological data for patients with UGB

Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 8Emergency

managed in the emergency departments are similar to the patients

department, Centre Hospitalier Annecy Genevois, Pringy Cedex,

treated in gastroenterology departments and/or in intensive care units.

Metz-Tessy, France.

More than one third of UGB patients are more than 75 years old.

References Additional file

1. Czernichow P, Hochain P, Nousbaum JB, Raymond JM, Rudelli A, Dupas JL, et al. Epidemiology and course of acute upper gastro-

Additional file 1: Appendix 1. Members of the Initiatives de Recherche

intestinal haemorrhage in four French geographical areas. Eur J

aux Urgences network. (DOCX 16 kb)

Gastroenterol Hepatol. 2000;12:175–181.

FEATURE 2. de Franchis R, Faculty BVI. Expanding consensus in portal

16. Paspatis GA, Matrella E, Kapsoritakis A, Leontithis C, Papanikolaou

hypertension: report of the Baveno VI consensus workshop:

N, Chlouverakis GJ, et al. An epidemiological study of acute upper

stratifying risk and individualizing care for portal hypertension. J

gastrointestinal bleeding in Crete, Greece. Eur J Gastroenterol

Hepatol. 2015;63:743–752.

Hepatol. 2000;12:1215–1220.

3. Hreinsson JP, Kalaitzakis E, Gudmundsson S, Björnsson ES. Upper

17. Kim JJ, Sheibani S, Park S, Buxbaum J, Laine L. Causes of bleeding

gastrointestinal bleeding: incidence, etiology and outcomes in a

and outcomes in patients hospitalized with upper gastrointestinal

population-based setting. Scand J Gastroenterol. 2013;48:439–447.

bleeding. J Clin Gastroenterol. 2014;48:113–118.

4. Thomopoulos KC, Vagenas KA, Vagianos CE, Margaritis VG, Blikas

18. Lanas A, Aabakken L, Fonseca J, Mungan ZA, Papatheodoridis GV,

AP, Katsakoulis EC, et al. Changes in aetiology and clinical outcome

Piessevaux H, et al. Clinical predictors of poor outcomes among

of acute upper gastrointestinal bleeding during the last 15 years.

patients with nonvariceal upper gastrointestinal bleeding in Europe.

Eur J Gastroenterol Hepatol. 2004;16:177–182. 5. van Leerdam ME. Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. 2008;22:209–224. 6. Theocharis GJ, Thomopoulos KC, Sakellaropoulos G, Katsakoulis E, Nikolopoulou V. Changing trends in the epidemiology and clinical outcome of acute upper gastrointestinal bleeding in a defined geographical area in Greece. J Clin Gastroenterol. 2008;42:128– 133. 7. Osman D, Djibré M, Da Silva D, Goulenok C, group of experts Management by the intensivist of gastrointestinal bleeding in adults and children. Ann Intensive Care. 2012;2:46. 8. Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152:101–113. 9. Chassaignon C, Letoumelin P, Pateron D, Group HD 2000 Upper gastrointestinal haemorrhage in emergency Departments in France: causes and management. Eur J Emerg Med Off J Eur Soc Emerg Med. 2003;10:290–295. 10. van Leerdam ME, Vreeburg EM, Rauws E a J, Geraedts A a M, Tijssen JGP, Reitsma JB, et al. Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol. 2003;98:1494–1499. 11. Vreeburg EM, Snel P, de Bruijne JW, Bartelsman JF, Rauws EA, Tytgat GN. Acute upper gastrointestinal bleeding in the Amsterdam area: incidence, diagnosis, and clinical outcome. Am J Gastroenterol. 1997;92:236–243. 12. Longstreth GF. Epidemiology of hospitalization for acute upper Gastroenterol. 1995;90:206–210. 13. Blatchford O, Davidson LA, Murray WR, Blatchford M, Pell J. Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study. BMJ. 1997;315:510–514. 14. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,

19. Zeitoun J-D, Rosa-Hézode I, Chryssostalis A, Nalet B, Bour B, Arpurt J-P, et al. Epidemiology and adherence to guidelines on the management of bleeding peptic ulcer: a prospective multicenter observational study in 1140 patients. Clin Res Hepatol Gastroenterol. 2012;36:227–234. 20. Nahon S, Hagège H, Latrive JP, Rosa I, Nalet B, Bour B, et al. Epidemiological and prognostic factors involved in upper gastrointestinal bleeding: results of a French prospective multicenter study. Endoscopy. 2012;44:998–1008. 21. Rotondano G. Epidemiology and diagnosis of acute nonvariceal upper gastrointestinal bleeding. Gastroenterol Clin N Am. 2014;43:643–663. 22. Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010;362:823–832. 23. Di Fiore F, Lecleire S, Merle V, Hervé S, Duhamel C, Dupas J-L, et al. Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study. Eur J Gastroenterol Hepatol. 2005;17:641–647. 24. Loperfido S, Baldo V, Piovesana E, Bellina L, Rossi K, Groppo M, et al. Changing trends in acute upper-GI bleeding: a population-based study. Gastrointest Endosc. 2009;70:212–224. 25. Villanueva C, Colomo A, Bosch A, Concepción M, HernandezGea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11–21. 26. Cuellar RE, Gavaler JS, Alexander JA, Brouillette DE, Chien MC, Yoo YK, et al. Gastrointestinal tract hemorrhage. The value of a nasogastric aspirate. Arch Intern Med. 1990;150:1381–1384. 27. Kessel B, Olsha O, Younis A, Daskal Y, Granovsky E, Alfici R. Evaluation of nasogastric tubes to enable differentiation between upper and lower gastrointestinal bleeding in unselected patients with melena. Eur J Emerg Med Off J Eur Soc Emerg Med. 2016;23:71–73. 28. Pateron D, Vicaut E, Debuc E, Sahraoui K, Carbonell N, Bobbia X, et al. Erythromycin infusion or gastric lavage for upper gastrointestinal

Vandenbroucke JP, et al. The strengthening the reporting of

bleeding: a multicenter randomized controlled trial. Ann Emerg

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guidelines for reporting observational studies. Lancet Lond Engl. 2007;370:1453–1457. 15. Rockall TA, Logan RF, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering committee and members of the

29. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, SoaresWeiser K, Uribe M. Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;(9):CD002907. 30. Longstreth GF, Feitelberg SP. Outpatient care of selected patients with

National Audit of acute upper gastrointestinal haemorrhage. BMJ.

acute non-variceal upper gastrointestinal haemorrhage. Lancet Lond

1995;311:222–226.

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gastrointestinal hemorrhage: a population-based study. Am J

Aliment Pharmacol Ther. 2011;33:1225–1233.

FEATURE

THE MICROBIOME-GUT-BRAIN AXIS AND ITS IMPLICATIONS FOR HEALTH AND DISEASE Dr Richard Day MA (Oxon), MBBS, MRCPsych - Medical Advisor, ADM Protexin https://www.protexin.com/

Introduction The microbiome-gut-brain axis is a complex, bi-directional communication system between the enteric nervous system, the brain and the gut microbiota(1). This system utilises a combination of neural, hormonal and immune channels to communicate(2). And, increasingly, the microbiome-gut-brain axis is implicated in multiple disease states(1,2). Manipulation of the gut microbiota for therapeutic benefit has long been associated with diseases of the gastrointestinal tract – there is now a considerable body of evidence for the efficacy of probiotic organisms in treating a multitude of GI diagnoses including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), infectious gastroenteritis and Clostridium difficile-associated diarrhoea (CDAD)(3–6). However, increasingly, researchers are looking at how manipulation of the gut microbiota can influence health outcomes in distant organs – including the brain.

The microbiome-gut-brain axis

The microbiome, dysbiosis and disease

The microbiome-gut-brain axis comprises the following fundamental

Recent efforts to catalogue the diversity of the human microbiome have

components:

revealed the adult GI tract is home to approximately 1000 bacterial species carrying a gene set up to 150x larger than that of the human

i) Neuroanatomic pathways, including the central nervous system

genome(8). Considerable variation exists in the microbiota profile

(CNS), the enteric nervous system (ENS) and the autonomic

from one individual to the next. Metagenomic studies have identified

nervous system

multiple factors that can affect the composition and diversity of the gut microbiome, including diet, geography, age and medication use(9).

GASTROENTEROLOGY TODAY - SPRING 2019

ii) Neuroendocrine pathways, which includes the hypothalamicpituitary axis iii) Immunological components, including Toll-like receptors (which can be activated by microbial components, triggering the release of cytokines) iv) Neurotransmitters and neuropeptides, produced both in the brain and in the gut by the microbiota

to occur in numerous illnesses, from IBS and IBD to obesity and even autism(8). Emerging evidence even supports the role of the microbiome – and dysbiosis – in influencing anxiety and depressive-like behaviours(7). And interestingly certain neurological diagnoses have also been identified as relevant to the microbiome-gut-brain- axis.

Overlap between IBS/GI diagnoses and migraine

The microbiome-gut-brain axis acts as a bi-directional signaling pathway that works to monitor and integrate gut functions as well as to link emotional and cognitive centres of the brain with peripheral intestinal mechanisms(7). The gut microbiota interacts not only with local intestinal cells and the ENS, but also directly with the CNS and through neuroendocrine and metabolic pathways(7).

Disruption in bacterial diversity – or dysbiosis – has been observed

An interesting correlation between certain GI diagnoses and migraine has been noted in a number of recent research papers(10). The HEAD-hunt study(11) looked at the relationship between GI symptoms and headache. This cross sectional study included more than 51,000 individuals in Norway and showed a significantly higher prevalence of headache among people

FEATURE who frequently experience GI complaints, when compared to controls. Interestingly, the association between headache and GI complaints increased with increasing headache frequency. In their 2018 paper, Martami et al. noted that in their study population, migraine had a significant association with IBS (OR = 5.16 95% CI 2.07-12.85, p=0.001). While in a 2016 cross-sectional study, women with IBS (particularly IBS-D variant) were noted to be particularly prone to having concomitant migraine(12). Furthermore, Lankarani et al.(13), in their 2017 population-based study, demonstrated a significant relationship between migraine and functional gastrointestinal diseases (IBS OR = 3.43 95% CI 2.40 – 4.89, p=0.001). But what is the significance of this association between migraine and GI disorders? While the exact pathophysiology of migraine is yet to be definitively characterized, there is emerging evidence that the GI system may play a significant role (14). Migraine attacks frequently occur with concomitant GI symptoms such as nausea, vomiting and gastroparesis, further implying a potential GI component to the pathophysiology. A better understanding of the pathophysiology of migraine, in relation to gastrointestinal function, may potentially reveal new therapeutic avenues.

Microbiota and migraine One explanation put forward for the association between migraine and gastrointestinal diagnoses is one of increased intestinal permeability(15). The ‘leaky guy hypothesis’ suggests that increased intestinal permeability may allow lipopolysaccharides and bacterial components into the bloodstream(16); these endotoxins may then predispose to or provoke migraines(15). Interestingly, gut permeability and inflammation appear to have a bi-directional relationship – increased gut permeability can trigger inflammation and vice versa(17,18). Migraine is thought to occur due to neurogenic inflammation and there is increasing evidence to show that a heightened inflammatory state contributes to trigeminal nerve activation and pain sensitization(17). There is a considerable body of evidence demonstrating that probiotics can reduce inflammation, increase short-chain fatty acid (SCFA) production and improve gut epithelial barrier function. Given this established evidence base for probiotics, and the neurogenic inflammation theory of migraine, Martami et al. hypothesized that probiotic supplementation might improve or attenuate migraine attacks – by improving the intestinal epithelial barrier function, reducing pro-inflammatory cytokines and stimulating the production of tight junctional proteins(17).

Implications for clinical practice The pathophysiology of migraine is extremely complex and yet to be definitively characterized, however this latest trial by Martami et al. adds to the evidence base that migraine is a multi-system condition. Moreover, this research contributes to the mounting body of evidence that the gut microbiota is capable of influencing the function of extra-intestinal organs, such as the brain, and provides a novel avenue for migraine prophylaxis that will no doubt be an area of considerable future clinical research. For any questions please contact medical@protexin.com References 1. Dumitrescu L, Popescu-olaru I, Cozma L, Tulb D, Hinescu ME, Ceafalan LC, et al. Review Article Oxidative Stress and the Microbiota-Gut-Brain Axis. Oxid Med Cell Longev. 2018;2018. 2. Zhao L, Xiong Q, Stary CM, Mahgoub OK, Ye Y, Gu L. Bidirectional gut-brainmicrobiota axis as a potential link between inflammatory bowel disease and ischemic stroke. J Neuroinflammation. 2018;3:1–11. 3. Chamberlain R, Lau C. Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Int J Gen Med. 2016 Feb;9:27. 4. D EAPP, D R, S TRB, Adamo CRD, Ph D, Wieland LS, et al. Probiotics and gastrointestinal conditions : An overview of evidence from the Cochrane Collaboration. Nutrition. 2018;45(2018):125–34. 5. Vandenplas Y. Probiotics and prebiotics in infectious gastroenteritis. Best Pract Res Clin Gastroenterol. 2016;30:49–53. 6. McKenzie YA, Thompson J, Gulia P, Lomer MCE. British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet [Internet]. 2016;29(5):576–92. Available from: http://doi.wiley.com/10.1111/jhn.12386 7. Carabotti M, Scirocco A, Antonietta M, Severi C. The gut-brain axis : interactions between enteric microbiota , central and enteric nervous systems. Ann Gastroenterol. 2015;203–9. 8. Harper A, Naghibi M, Garcha D. The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome. Foods [Internet]. 2018;7(2):13. Available from: http:// www.mdpi.com/2304-8158/7/2/13 9. Wang W, Xu S, Ren Z, Tao L, Jiang J, Zheng S. Application of metagenomics in the human gut microbiome. World J Gastroenterol. 2015;21(3):803–14. 10. Martami F, Ghorbani Z, Abolhasani M, Togha M, Meysamie A, Sharifi A, et al. Comorbidity of gastrointestinal disorders, migraine, and tension-type headache: a cross-sectional study in Iran. Vol. 39, Neurological Sciences. 2017. 1-8 p. 11. AH Aamodt, LJ Stovner, K Hagen J-AZ. Comorbidity of Headache and Gastrointestinal Complaints. The Head-HUNT Study. Cephalalgia. 2008;28(2):144–51. 12. Perveen I, Parvin R, Saha M, Bari S. Prevalence of Irritable Bowel Syndrome ( IBS ), Migraine and Co-Existing IBS- Migraine in Medical Students. J Clin Diagnostic Res. 2016;9–13. 13. Lankarani KB, Akbari M, Tabrizi R. Association of Gastrointestinal Functional Disorders and Migraine Headache : a Population Base Study. Iran Assoc Gastroerterology Hepatol [Internet]. 2017;9(3):139–45. Available from: http:// dx.doi.org/10.15171/mejdd.2017.64 14. Doulberis M, Saleh C, Beyenburg S. Is There an Association between Migraine and Gastrointestinal disorders? J Clin Neurol. 2017;13(3):215–26. 15. N.M. de Roos, C.G.T. Giezenaar, J.M.P. Rovers, B.J.M. Witteman MGS and S van H. The effects of the multispecies probiotic mixture Ecologic ® Barrier on migraine : results of an open-label pilot study. Benef Microbes. 2015;6(5):641–6. 16. Parlesak A, Schäfer C, Schütz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease**Dedicated to Dr. Dr. Herbert Falk, Director of the Falk Foundation, on the occasion of his 75th birthday. J Hepatol [Internet]. 2000;32(5):742–7. Available from: http://www.sciencedirect. com/science/article/pii/S0168827800802421 17. Martami F, Togha M, Seifishahpar M, Ghorbani Z, Ansari H, Karimi T, et al. The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics : A randomized double-blind controlled trial. 2019;0(0):1–13. 18. Marchiando AM, Graham WV, Turner JR. Epithelial Barriers in Homeostasis and Disease. Annu Rev Pathol Mech Dis [Internet]. 2010 Jan 1;5(1):119–44. Available from: https://doi.org/10.1146/annurev.pathol.4.110807.092135

GASTROENTEROLOGY TODAY - SPRING 2019

In their subsequent 2019 double-blind randomized controlled trial (RCT) Martami et al. assessed whether supplementation with a 14-strain probiotic was effective in alleviating the frequency, severity and duration of migraine attacks(17). The trial included individuals diagnosed with either episodic migraine (EM) or chronic migraine (CM), as defined by the International Classification of Headache Disorders. Measured against placebo controls, individuals that received the multispecies probiotic experienced a statistically and clinically significant reduction in frequency and severity of migraine attacks, in addition to a reduction in weekly abortive drug usage. Following the probiotic intervention the mean monthly frequency of migraines in the episodic migraine group declined from 6.59 to 3.95 (p<0.001), and did not change significantly within the placebo group. The mean monthly frequency of migraine attacks also significantly declined in the CM probiotic-supplemented group, from 21.57 to 11.9 (p<0.001) again with no significant change in the placebo control group. Interestingly the researchers were not able to demonstrate any statistically significant change in inflammatory markers following

probiotic supplementation, so while the clinical endpoints are clear, the underlying mechanism of action is yet to be fully characterized.

FEATURE

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Dr Matthew Banks leads our team of expert gastroenterologists, nurses and decontamination technicians to provide weekend general outpatient clinics and endoscopy services.

Criteria & Quality We select Endoscopists with an endoscopy orientated career path and performance measures above the national average. JAG audit data is constantly monitored to ensure ongoing quality. Furthermore, we have a clinical governance department that is crucial to maintaining quality and safety but also provides support to both Endoscopists and the units within which we work.

We have streamlined our services to enable us to take ownership of the entire patient pathway from first attendance through to endoscopy, follow up and discharge as appropriate.

We manage all administration that is associated with each patient episode, approving clinic letters, reviewing results of investigations and ensuring all outcomes are communicated to the patient and their general practitioner. We have also introduced virtual follow up and virtual histology clinics into the service.

We provide tailored solutions to manage capacity from straight forward supply of staff to a team based managed solution to a full patient pathway including pathology review. Our commitment to improving the NHS experience Like the NHS Trusts we work with, patient care is at the centre of everything we do. By using any spare weekend capacity within a Trust, the 18 Week Support insourcing teams are able to see a high volume of patients in a short space of time, in the familiar surrounding of the NHS Trust. An ethical company We’re an ethical and transparent company that’s financially accountable and financially responsible. We’re committed to the NHS and the delivery of high-quality care, and to helping Trusts reduce RTT waiting times.

How our insourcing service works 18 Week Support Clinical team

NHS Facility

Weekend

NHS Staff

NHS processes

Happy patient

Who we’re looking for We are interested in meeting with Consultant Gastroenterologists, senior nurses and clinical nurse specialists throughout the UK. Our remuneration package is second to none and is per session rather than per case which allows our teams to work in a safe and calm environment’ About you If you have an excellent NHS record and want to help clear NHS waiting list backlogs, reduce RTT waiting times and provide high-quality patient care, get in touch by calling on 020 3892 6162 or email Gastro.Recruitment@18weeksupport.com

Matthew Banks Clinical Lead for Gastroenterology 18 Week Support 18 Week Support www.18weeksupport.com A CQC Registered provider offering high quality clinical support services to NHS Trusts throughout the UK.

GASTROENTEROLOGY TODAY - SPRING 2019

Our team of gastroenterologists manage all other aspects of upper and lower GI disorders including; Dyspepsia GORD IBS Gastric ulcers Swallowing difficulties

Raising the standard of care Our clinical teams are committed to working weekends to provide a wide range of clinical services. Many of our clinical leads are experts in their field. So not only do patients benefit from the work our teams do, there is also an opportunity for NHS Trust teams to improve efficiencies through new techniques or approaches.

London 3rd Floor, 19-21 Great Tower Street, London EC3R 5AR 020 3869 8790 Edinburgh 9-10 St. Andrew Square Edinburgh EH2 2AF

FEATURE

A NEW PATHWAY FOR FAECAL CALPROTECTIN TESTING IN PRIMARY CARE Improving Patient Care and Access, Saving the NHS £65M A recent publication from BIVDA and Innovate UK1 identifies three

Health Economic studies demonstrate considerable financial benefits

simple tests that could save the NHS £6.9 Billion over a 5 year

for primary care, capacity benefits for secondary care and most

period if implemented more widely.

importantly, better patient experience, through faster diagnosis. Highly significant is the reduction in the number of patients who need to

Faecal calprotectin is one of the tests heralded and it alone is estimated

undergo risky, uncomfortable and costly colonoscopies.

to offer savings of £65 million to the NHS. This could be achieved if

In the roll-out of the York Faecal Calprotectin Care Pathway (on which

calprotectin testing was more widely available to assist in the diagnosis

the above algorithm is based), compliance was 85% and so the actual

of Inflammatory Bowel Disease (IBD).

(rather than optimal) saving amounted to between £60,000 and nearly

Although calprotectin is now well established and routinely in use in

used for the laboratory analysis within this pathway (see

many hospitals, it is often restricted as a secondary care test. However,

www.calprotectin.co.uk).

£100,000 per 1000 patients3. The BÜHLMANN fCAL® ELISA is being

if calprotectin was made available more extensively as a primary care test then significant savings could be achieved in outpatient and

These savings were achieved by correctly supporting the diagnosis of

colonoscopy resource.

IBS within primary care, avoiding 100–150 colonoscopies and 140–190 gastroenterology outpatient appointments.

The challenge is that uncontrolled access to faecal calprotectin testing could result in an increase in cost and greater demands on limited

The AHSN Network is actively engaged in supporting the roll out of

resources (<50μg/g is widely accepted as a negative result, but this

this improved pathway across the country after work in Yorkshire and

doesn’t mean that >50μg/g is positive).

Humber demonstrated significant benefits to the health economy in the region.

In order to address these issues, a new pathway for the use of faecal calprotectin testing in primary care is being rolled out across England

If you would like to get involved in delivery of the pathway across your

through the national Academic Health Science Network (AHSN). See

area, or want any further information please contact your local AHSN or

Figure 1.

email Victoria Hilton at victoria.hilton@yhahsn.com

The pathway is designed to provide GPs with a risk assessment of a

References

patient’s likely condition based on the results of the faecal calprotectin GASTROENTEROLOGY TODAY - SPRING 2019

test. This helps to provide greater confidence in decisions to refer patients to secondary care. The new pathway will help assist in cases where there is uncertainty between the diagnosis of Irritable Bowel Syndrome (IBS) and

1. BIVDA and Innovate UK: Three simple tests could save the NHS at least £6.9 billion. www.bivda.org.uk/3_simple_tests.pdf 2018 2. www.pcc-cic.org.uk/article/updatedguidance-help-gps-easilydiagnose-seriousbowel-conditions

Inflammatory Bowel Disease (IBD). An NHS England Task and Finish group has been formed to create a consensus report on optimising faecal calprotectin testing using this new pathway.

3. Turvill J. et al. Frontline Gastroenterology 2018;0:1-10. Evaluation of the clinical and cost effectiveness of the York Faecal Calprotectin Care Pathway

The paper is available through the primary care commissioning website2. It has been endorsed by NICE, Crohn’s and Colitis UK and the

For further information on calprotectin testing please visit

British Society of Gastroenterologists.

www.calprotectin.co.uk

FEATURE

“The development of this algorithm offers significant benefits to the patient’s experience along with savings across the health economy. Its adoption by clinical colleagues is welcomed.” 2 Figure 1.

GASTROENTEROLOGY TODAY - SPRING 2019

FEATURE

INDEPENDENTLY SUPPORTED BY RESEARCH TO ARRIVE, SURVIVE, AND THRIVE IN THE GUT A unique, water-based formulation to help support the gut microbiome ts multi-strain bacteria arrives  I in a live and active state, ready to act in the gut  Its Its water-based nature survives stomach acid, allowing the bacteria to reach the gut intact GASTROENTEROLOGY TODAY - SPRING 2019

 Bacteria are clinically proven to rapidly colonise in the gut, contributing to gut microbiome balance To find out more about SymproveTM contact 01252 413 600 or support@symprove.com

www.symprove.com/bioscience References: 1. Freuda-Agyeman, M et al. (2014). Comparative survival of commercial probiotic formulations: tests in biorelevant gastric fluids and real-time measurements using microcalorimetry. Beneficial Microbes. 6(1). 141-151 2. Data on file. Results from a SymproveTM Customer Survey 3. Wang, B et al. (2017). The human microbiota in health and disease. Engineering 3(1). 71-82 4. Sisson G, Ayis S, Sherwood RA and Bjarnason I. (2014). Randomised clinical trial: A liquid multi-strain probiotic vs. placebo in the irritable bowel syndrome – a 12 week double-blind study. Aliment Pharmacol Ther 40. 51-62

ADVERTORIAL FEATURE

JOHN RADCLIFFE HOSPITAL, OXFORD The Need

The Vanguard Solution

The John Radcliffe Hospital services a population of 640,000 people

The purpose-built Endoscopy Decontamination Unit featured a plant room,

and face the challenges of increased demand for endoscopy

clean room, dirty room, a pass-through endoscope washer and disinfector

procedures as outlined in the NHS’s Long-Term Plan to improve

area, and a staff welfare area. The unit is fully HTM compliant, including

cancer diagnostics rates with earlier detection. The hospital identified

all aspects relating to fire safety and water quality. Vanguard designed the

that the 10-year-old Endoscope

unit to have windows and glass

Decontamination facility required

doors to flood in natural light to

refurbishment and the installation of more reliable, compliant and higher-tech equipment to cope with the continued demand. The cost of this refurbishment programme would be £2.3 million and entailed the closure of its Endoscopy Decontamination department for several months. The hospital needed a solution that would avoid disruption and

“I will admit in the beginning I was concerned about the mobile unit however after working in there, I was really pleased. It has been a godsend and the team really love working in there, they especially love having windows.” Lindsey Gander, Decontamination Supervisor (Endoscopy)

create an enjoyable and safe work environment for hospital employees. To be able to disinfect all channelled flexible scopes, the unit was equipped with modern and highspec equipment that was on par with the hospitals’ own technology. This equipment included an electronictracking system, automated water system, a leak detector, and an anti-fume and anti-spill chemical cabinet. Vanguard also provided

maintain its patient numbers and safety levels. The closure of a vital service was not an option, therefore

a facilitator to work alongside the hospital team to ensure the smooth and

the hospital considered a variety of opportunities including temporary

efficient running of the unit.

modular buildings, renting or buying a mobile unit, and even moving to another estate. After working with Vanguard Healthcare Solutions in previous years, the Vanguard mobile Endoscopy Decontamination unit was the only solution that met their requirements and budget. The Vanguard Plan Working with the hospital’s clinical, management and estate teams, Vanguard Healthcare Solutions designed and built an Endoscopy Decontamination mobile unit, the first of its kind in the Vanguard fleet,

The Outcome Since the Endoscopy Decontamination unit was installed in August 2018, the hospital has managed to maintain its services at full capacity and without disruption. Almost 10,000 scopes have been decontaminated so far and the unit has enabled the hospital to continue to meet the criteria needed for JAG accreditation. With the demand for Endoscopy increasing by 8-10% each year, the Vanguard unit has allowed the hospital to keep its Endoscopy Decontamination services running at 6 days a week along with two additional late evenings.

to suit the hospital needs and specifications. This included four AERs, two drying cabinets, a pass-through hatch and a RO system that offers 100% redundancy. After conducting a site survey, the unit was delivered and installed by a dedicated and highly-skilled transport and logistics team, and placed towards the back of the hospital. Vanguard ensured the unit was in place and commissioned to meet the timeframes needed for a smooth crossover between the existing facilities and transfer to the mobile unit to maintain service, quality and to work at full capacity.

The unit has provided flexibility and time to the hospital, giving them enough time to efficiently train staff on the new equipment as well as continuing to maintain their service levels at the same time.

www.vanguardhealthcare.co.uk

GASTROENTEROLOGY TODAY - SPRING 2019

Stats • Over 10,000 scopes disinfected so far • On average 109 scopes per day • Maintains JAG accreditation

ADVERTORIAL FEATURE

HOW CAN WE IMPROVE ENDOSCOPY AND COLONOSCOPY RECOVERY FOR PATIENTS? By Dr Colin Hayward, Medical Director, Symprove Ltd Our knowledge of the microbiome and its inﬂuence on human

changes to the gut flora [2]. This essentially found that probiotics can

health has greatly increased over the last decade and continues to

help make the microbiota of healthy human donors, healthier and

grow. It is now time to see how we can tangibly benefit the way we

positively change the proportion of bacterial groups in the gut flora.

manage gut health. In relation to endoscopy, some advice (from hospital patient leaflets) It is well known that invasive procedures, such as endoscopy are likely

states that eating yoghurt or kefir, taking a probiotic supplement, eating

to disrupt the gut microbiome – both from diet changes, laxatives and

a diet rich in prebiotics and avoiding processed foods for several days

sedatives to prepare for the procedure, to the actual procedure itself [1-

will gently and naturally restore a patient’s gut microbiome to a healthy

3]. This can also remove ‘good bacteria’ and disrupt the balance of the

balance. We now need to provide more detailed advice, for example

gut flora. Pre-procedure advice is very clear, but have we moved forward

probiotics can be very different with varying evidence of effectiveness.

with post-procedure advice? Why aren’t we advising patients to take

Most recent evidence has shown that live, multi-strain, water-based

extra steps to restore balance in the gut microbiome?

liquid probiotics are able to arrive, survive and thrive in the gut, enabling the microbiome to be fed here [5].

Typically, endoscopy patients will take a laxative to empty their colon before the procedure, to evacuate most or all of the stool from a

There are no standardised colonoscopy or endoscopy after-care

patient’s colon [1]. Bowel preparations can also affect markers of

guidelines in the UK by NICE or the British Society of Gastroenterology

proliferation in the intestinal epithelium, and thus could theoretically

(BSG). After-care advice varies across hospitals and many have their

affect the mucosa-associated microbiota [1] The procedure itself

own patient information leaflets, which details preparations for and

involves physical disruption to the colon, which will of course, affect the

recovery after an endoscopy. None however, mention taking steps to

structure of the gastrointestinal tract and the balance of the gut bacteria. Two recent studies (Shobar et al. and Drago et al.) have highlighted the negative impact on the gut microbiota from using either a sodium phosphate-based or a polyethylene glycol-based preparation prior to colonoscopy. Both immediately, and one month after the procedure there was a noticeable impact on gut microbiota at a class level with an increase in proteobacteria and a decrease in firmicutes. More specifically a reduction in Lactobacillaceae and an increase in Enterobacteriaceae, Rikenellaceae, Eubacteriaceae and GASTROENTEROLOGY TODAY - SPRING 2019

Streptococcaceae were also observed [2,3]. Some studies have gone further to look at the impact of combating the impact of colonoscopy on gut microbiota, through the use of probiotics. In a double-blind, placebo-controlled trial of 104 patients with constipation it was found that pre-treatment with probiotics resulted in multiple benefits; an increase in effective bowel cleansing, improved colonic mucosa visualisation during colonoscopy and reduction of intestinal distress symptoms following the colonoscopy [4]. Several studies into probiotics have shown their effectiveness to achieve a healthy balance of ‘good’ bacteria in the gut microbiome. For example, results from a recent University College of London study into probiotics, using a simulated gastrointestinal system, found that feeding the microbiome with a probiotic containing live bacteria, resulted in

replenish gut flora and avoid dysbiosis, which can lead to immune dysfunction [6]. There is no doubt that endoscopies and colonoscopies are vital tools in screening. However, there are steps that could be taken to maintain or re-establish a healthy microbiome following these procedures to help reduce the side effects on the gut microbiota and subsequently the immune system. References 1 Croucher LJ, Bury JP, Williams EA et al. Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study. BMC Gastroenterol; 2008; 8:54. 2 Moens F et al. A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro. International Journal of Pharmaceutics; 2018; 555: 1-10 3 Drago L, Toscano M, De Grandi R, Casini V, & Pace F. Persisting changes of intestinal microbiota after bowel lavage and colonoscopy. Eur J Gastroenterol Hepatol; 2016; 28(5): 532–537 4 Lee H. A feasibility study of probiotics pretreatment as a bowel preparation for colonoscopy in constipated patients. Dig Dis Sci; 2010; Aug;55(8): 2344-51. 5 Fredua-Agyeman, M and Gaisford, S. Comparative survival of commercial probiotic formulations: tests in biorelevant gastric fluids and real-time measurements using microcalorimetry. Beneﬁcial Microbes; 2014; 6(1): 141-151 6 Shi N. et al. Interaction between the gut microbiome and mucosal immune system. Mil Med Res; 2017; Spr 27(4): 14

The only licensed treatment for the reduction in recurrence of overt hepatic encephalopathy (OHE)1

FEATURE

At home they are still at risk; …TARGAXAN® rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy.2

Long-term secondary prophylaxis in hepatic encephalopathy (HE)3 Pregnancy and lactation: Rifaximin is not recommended during pregnancy. The benefits of rifaximin treatment should be assessed against the need to continue breastfeeding. Side effects: Common effects reported in clinical trials are dizziness, headache, depression, dyspnoea, upper abdominal pain, abdominal distension, diarrhoea, nausea, vomiting, ascites, rashes, pruritus, muscle spasms, arthralgia and peripheral oedema. Other effects that have been reported include: Clostridial infections, urinary tract infections, candidiasis, pneumonia cellulitis, upper respiratory tract infection and rhinitis. Blood disorders (e.g. anaemia, thrombocytopenia). Anaphylactic reactions, angioedemas, hypersensitivity. Anorexia, hyperkalaemia and dehydration. Confusion, sleep disorders, balance disorders, convulsions, hypoesthesia, memory impairment and attention disorders. Hypotension, hypertension and fainting. Hot flushes. Breathing difficulty, pleural effusion, COPD. Gastrointestinal disorders and skin reactions. Liver function test abnormalities. Dysuria, pollakiuria and proteinuria. Oedema. Pyrexia. INR abnormalities. Legal category: UK - POM, Ireland - Prescription only. Cost: UK - Basic NHS price £259.23 for 56 tablets. Ireland - €262.41 for 56 tablets Marketing Authorisation number: UK - PL 20011/0020. Ireland - PA 102/29/1 For further information contact: Norgine Pharmaceuticals Limited, Norgine House, Moorhall Road, Harefield, Middlesex, United Kingdom UB9 6NS Telephone: +44(0)1895 826606 E-mail: medinfo@norgine.com Ref: UK/XIF5/0318/0386 Date of preparation: March 2018 United Kingdom - Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Medical Information at Norgine Pharmaceuticals Ltd on 01895 826606.

Ireland - Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. Adverse events should also be reported to Medical Information at Norgine Pharmaceuticals on +44 1895 826606. References: 1. National Institute for Health and Care Excellence. Rifaximin for preventing episodes of overt hepatic encephalopathy: appraisal guidance TA337 for rifaximin. Available from: http://www.nice.org.uk/guidance/ta337 2. TARGAXAN® 550 Summary of Product Characteristics. Available for the UK from: https://www.medicines. org.uk/emc/medicine/27427. Available for Ireland from: http://www.medicines.ie/medicine/15936/SPC/ TARGAXAN+550mg+film-coated+tablets/. 3. Mullen KD, et al. Clin Gastroenterol Hepatol 2014;12(8):1390-97. Product under licence from Alfasigma S.p.A. TARGAXAN is a registered trademark of the Alfasigma group of companies, licensed to the Norgine group of companies. NORGINE and the sail logo are registered trademarks of the Norgine group of companies. UK/XIF5/1118/0457 Date of preparation: November 2018.

GASTROENTEROLOGY TODAY - SPRING 2019

Targaxan 550 mg film-coated tablets (rifaximin-α). REFER TO FULL SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) BEFORE PRESCRIBING Presentation: Film-coated tablet containing rifaximin 550 mg. Uses: Targaxan is indicated for the reduction in recurrence of episodes of overt hepatic encephalopathy in patients ≥ 18 years of age. Dosage and administration: Adults 18 years of age and over: 550 mg twice daily, with a glass of water, with or without food for up to 6 months. Treatment beyond 6 months should be based on risk benefit balance including those associated with the progression of the patients hepatic dysfunction. No dosage changes are necessary in the elderly or those with hepatic insufficiency. Use with caution in patients with renal impairment. Contraindications: Contraindicated in hypersensitivity to rifaximin, rifamycin-derivatives or to any of the excipients and in cases of intestinal obstruction. Warnings and precautions for use: The potential association of rifaximin treatment with Clostridium difficile associated diarrhoea and pseudomembranous colitis cannot be ruled out. The administration of rifaximin with other rifamycins is not recommended. Rifaximin may cause a reddish discolouration of the urine. Use with caution in patients with severe (ChildPugh C) hepatic impairment and in patients with MELD (Model for End-Stage Liver Disease) score > 25. In hepatic impaired patients, rifaximin may decrease the exposure of concomitantly administered CYP3A4 substrates (e.g. warfarin, antiepileptics, antiarrhythmics, oral contraceptives). Both decreases and increases in international normalized ratio (in some cases with bleeding events) have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of treatment with rifaximin. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. Ciclosporin may increase the rifaximin Cmax

NEWS Rapid Diagnostic Centres are the key to early diagnosis of pancreatic cancer according to Leading Gastroenterologist A leading Consultant Gastroenterologist and Hepatologist believes that the rollout of Rapid Diagnostic Centres (RDCs), also known as MDCs or Multidisciplinary Diagnostic Centres, outlined in the new NHS long term plan “could be truly lifesaving” by significantly improving early diagnosis of one of the most notoriously difficult forms of cancer, pancreatic cancer. Dr Andrew Millar, who jointly leads the UCLH Cancer Collaborative MDCs, on which RDCs have been modelled, has already shown encouraging results in detecting pancreatic cancer - the quickest killing cancer.

percent are currently diagnosed after attendance at A&E with worse outcomes as a result. The NHS long term plan prioritises faster diagnosis for suspected cancer and has confirmed a nationwide roll-out of RDCs, designed to deliver a confirmation of a diagnosis of cancer, or not, within 28 days of referral by enabling patients with vague symptoms to rapidly access a range of tests in one unit. Dr Millar, the joint Clinical Lead for MultiDisciplinary Diagnostic Centres for the UCLH Cancer Collaborative, said: “We know that pancreatic cancer normally presents with nonspecific symptoms and is notoriously difficult to diagnose, so it is obviously one of the cancers we should be focusing on in the roll out of RDCs. We’ve already seen that pancreatic cancer is statistically the most frequent cancer diagnosed through this pathway, so there is no doubt that the RDCs could be truly lifesaving for people with pancreatic cancer.

“One of the many successes of the MDC Faster diagnosis for pancreatic cancer is model, that we hope to see scaled up through crucial, as 60 per cent of patients are not the RDC roll-out, is the revised role of Cancer diagnosed until the cancer is at an advanced Nurses Specialists (CNS). In the MDC model, stage. One in four pancreatic cancer patients die within a month of diagnosis and 12/01/2017 up to 50 specialist nurses are assigned to patients at ScheBo_GastroToday_Jan_2017 17:18 the point of referral, rather than at diagnosis, so they receive support through the diagnosis process and drastically improve patient experience.”

GASTROENTEROLOGY TODAY - SPRING 2019

Dr Millar will be sharing his thoughts on the benefits of RDCs for pancreatic cancer at the charity Pancreatic Cancer UK’s Annual Summit. His expert views will feature in a discussion around the impact of the NHS long term plan on pancreatic cancer patients. During the session the panellists will discuss opportunities the plan presents to accelerate success for pancreatic cancer. The Summit, staged annually since 2012, will feature a variety of specialist talks including ‘Accelerating

early diagnosis research’ with Professor Steve Pereira (University College London), ‘Diagnostic PET-CT scanning’ with Professor Paula Ghaneh (University of Liverpool) and ‘Precision radiotherapy’ with Dr Ganesh Radhakrishna (The Christie Foundation NHS Trust). Anna Jewell, Director of Operations at Pancreatic Cancer UK, said: “Faster diagnosis is pivotal in the fight against pancreatic cancer so a renewed focus from Government on achieving this is very welcome. We need to ensure that NHS England prioritises pancreatic cancer in the roll-out of rapid diagnostic clinics and timed diagnostic pathways so we can achieve the improvements in survival that have been so badly needed for over 40 years.” The Pancreatic Cancer UK Annual Summit: Accelerating Success, takes place on the 14th March 2019, bringing together health professionals, leading researchers, policy makers, charities and people affected by the disease. In addition to specialist talks on breakthroughs in diagnosis, delegates will learn about cutting-edge research and hear first-hand accounts from pancreatic cancer patients. To find out more about the event or register to attend please visit: www.pancreaticcancer.org.uk/summit

Reduce Your Costs for Biological Sample Transport How do you package your send-away pathology samples? Are you spending too much time and money on packaging your samples correctly? If you are currently wrapping tubes and using boxes to transport samples by courier or Royal Mail, this could be costing you a lot more and taking much longer than necessary. The Transport of Dangerous Goods Regulations require patient specimens and other biological samples to be transported according to UN3373 Biological Substance Category B, P650 Packaging Instruction. However, compliant packaging requires multiple elements that can result in a bulky package which is expensive to transport. One pathology laboratory, sending away 1000 samples per month, has recently switched to the SpeciSafe® complete secondary sample packaging system which will save them over £21,000 per year. SpeciSafe® fulfils multiple requirements of the packaging regulations. The compact, clamshell design holds primary 95kPa containers in rigid, cushioned, pre-moulded compartments, so they are protected and multiple vials are separated from each other. The bonded ultra-

NEWS absorbent lining will soak up the entire liquid volume in the event of a primary container breach. The SpeciSafe is leak-proof when closed and its rigidity means only a flexible outer envelope is required for road transport. SpeciSafe also delivers further benefits. It is very quick and easy to use and the transparent front means any leakages from the primary container are easily visible. Patient information is easily seen and can be read by barcode readers without unpacking. Samples can be posted by Royal Mail at large letter rates which could save over £2 per package, provided the primary container is less than 25mm in diameter and the sample volume does not exceed 50ml. Please visit www.un3373.co.uk for further information or contact Alpha Laboratories on 0800 38 77 32 or email marketing@ alphalabs.co.uk

Endoscopy Unit Awarded JAG Accreditation at Highgate Private Hospital We are delighted to announce that Highgate Private Hospital’s Endoscopy Department

has been awarded JAG accreditation. JAG accreditation QA standards were created to support the achievement of high-quality, safe and appropriate endoscopy services. This prestigious accreditation is only awarded to endoscopy units that provide a high quality service for patients and demonstrate clear evidence that they have met all of the JAG standards.

Highgate Private Hospital Director, Steve Patrick, praised and congratulated the Endoscopy team for their hard work in gaining JAG accreditation, ‘”I am delighted that our team have been given the recognition they deserve and would like to thank them for their outstanding work. This accreditation reinforces our commitment to providing clinical excellence for the patients having procedures here.”

Highgate Private Hospital based in North London provides a welcoming environment with its dedicated newly developed, selfcontained Endoscopy Suite and procedure room which opened in January 2014. The unit is staffed by dedicated, endoscopy trained personnel and supported by a highly experienced clinical and managerial team.

Christine Etherington, Director of Clinical Services and Quality Governance, said “Having JAG accreditation is the gold standard of endoscopy regulation and safety. This gives the clinical staff team and our Consultant doctors at Highgate the confidence that our patients are not only safe, but that we regulate monitor and review our patients’ outcomes to achieve this gold standard. We are immensely proud of our Endoscopy team and the “can co” attitude they put in to achieving JAG accreditation. For a new unit to receive this stamp of approval on first submission is quite simply amazing.”

Lead Consultant, Dr Deepak Suri, Consultant Gastroenterologist said “The entire department has worked hard over the last year to achieve JAG recognition by investing in the new unit which is a clean and modern endoscopy environment. We are proud that the hospital has been recognised for the high quality and safety of the endoscopy services it provides and look forward to constantly improving on this great result.”

Find out more about our Endoscopy Services by visiting our treatment pages here https:// www.highgatehospital.co.uk/generalsurgery/endoscopy/

driving scientific advancements in digestive health October 19-23, 2019 Venue: Fira Gran Via, Barcelona UEG President Professor Paul Fockens discusses why he is looking forward to UEG Week 2019

The UEG Scientific Committee is developing a state-of-the-art scientific programme, featuring the latest advancements and most exciting research in digestive health. An inclusive offering is provided for all attendees, whatever their level of expertise, featuring a broad variety of symposia and session types that includes live endoscopies, video case sessions and interactive formats allowing delegates the opportunity to passionately debate with fellow attendees. The two-day Postgraduate Teaching Programme will provide profound updates

on a wide range of gastrointestinal and hepatology topics that suit both gastroenterologists in training as well as established physicians and general practitioners. The programme focuses on the relevance for the clinical day-to-day business and enables participants to get perfectly prepared for their professional career. 2019 marks year 3 of our rolling 3-year curriculum. I am anticipating a very exciting week of scientific advances and updates from leading digestive health experts and thoroughly look forward to welcoming new and returning delegates to UEG Week Barcelona 2019. To find out more, visit www.ueg.eu/week

Early bird fe

until May

16, 2019

Abstract submission open until April 26, 2019

GASTROENTEROLOGY TODAY - SPRING 2019

UEG Week is the largest and most prestigious gastroenterology meeting of its kind, with more than 12,500 delegates from over 110 countries worldwide.

NEWS Launch of first licensed drug for Eosinophilic Oesophagitis a significant step forward for UK sufferers

EoE is clinically characterized by oesophageal

manages the symptoms but not the cause of

dysfunction and histologically characterized by

EoE and often has to be repeated.

an eosinophil-rich inflammation, most probably caused by common food allergies or other

‘The UK launch of Jorveza represents an

environmental triggers. Often misdiagnosed

extremely positive development for those living

as GORD (gastro oesophageal reflux

with EoE,’ says Dr Riadh Jazrawi, Medical

disease), adult symptoms include dysphagia,

Director of Dr Falk Pharma UK. ‘Not only does

bolus obstruction and chest pain related

it provide innovative drug delivery targeted

Dr Falk Pharma UK announces the UK launch

to swallowing, heartburn and regurgitation.

directly to the area of inflammation, Jorveza

of Jorveza, the first globally licensed drug

In children they can include reflux-related

also has proven patient and disease efficacy

approved for the treatment of the immune

symptoms, nausea, vomiting, abdominal pain,

outcomes compared to placebo. Further, it is

mediated, chronic and progressive disease of

refusal to eat or failure to grow. 2 Untreated

easy to take, with few side effects, providing

EoE can lead to oesophageal remodelling

EoE patients and clinicians with a highly

including the formation of strictures and EoE is

beneficial alternative to current DIY unlicensed

the cause of more than 50% of all emergency

treatments.’

the oesophagus, Eosinophilic Oesophagitis (EoE). Jorveza is an orodispersable tablet containing the topical corticosteroid budesonide and is specifically designed to deliver directly to the inflammation within the oesophageal mucosa. (NOTES). In a randomised, controlled clinical trial, Jorveza demonstrated high rates of clinical and histological remission and high patient tolerability, with few side effects.1 Its UK

presentations for oesophageal food bolus EoE is most frequently diagnosed in males

impactions.3

aged 30-50 although it can be found in all Up until now treatment for EoE has been

age groups. Annual incidence rates of EoE

focussed around three areas; dietary

in western countries are 1.7 per 100,000 with

exclusion, drugs and dilation. Dietary exclusion

prevalence rates of 16.1 per 100,000. However,

is generally considered hard to maintain and

for patients with oesophageal symptoms

costly to follow up, whilst current steroid drug

who undergo gastroscopy the prevalence

therapy delivery is not optimised for delivery

is 7% whilst in patients with dysphagia and

launch has been welcomed by clinicians and

to the oesophagus and relies on off-licence

bolus obstruction, prevalence increases to

patient groups as a significant step forward

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Efficacy and Safety Of Budesonide Orodispersible Tablets in Active Eosinophilic Oesophagitis: Results from a Randomised, Double-blind, Placebo-Controlled, Pivotal, European Multicentre Trial (Eos-1) A. Straumann1, A. J. Lucendo Villarin2, S. Miehlke3, M. Vieth4, et al United European Gastroenterology Journal 5(5S) A146-A147 Eosinophilic esophagitis N Engl J Med. 2015;373(17):1640–8. Furuta GT, Katzka DA. 3 Prevalence of eosinophilic oesophagitis in adults presenting with oesophageal food bolus obstruction. World J Gastrointest Pharmacol Ther 2015;6:244–247. Heerasing N, Lee SY, Alexander S, et al

NEWS EoE only received classification in the 1990s and disease awareness amongst both clinicians and the general public is thought to be low. Currently, average time to diagnosis is up to 8.1 years6 whilst a 2016 study found only 22% of patients reporting to A&E with food bolus and dysphagia were biopsied to confirm diagnosis of the condition.7 ‘EoE has a considerable impact on the quality of life and the self-esteem of patients,’ says Professor Stephen Attwood, Consultant Surgeon and

Point of Care Calprotectin & TDM

Honorary Professor at Durham University, and one of the first doctors to identify and highlight the condition. ‘Not only do many develop adaptive eating strategies such as prolonged chewing, drinking copious amounts of liquids and avoiding certain foods, they also dread social situations and even eating with their families. Young adults can be labelled as having psychological eating disorders whilst young children often fail to thrive and can suffer from malnutrition. ‘Therefore, it is vital that there is greater general awareness of the condition. A key message for clinicians has to be that any patient who presents with pain on eating or feeling that food is sticking in the throat – especially if they have a history of allergic illnesses such as rhinitis, asthma and eczema – should be referred for biopsies with a specific request to look for eosinophils. And, when diagnosed, a longterm topical steroid developed directly to the inflammation is the only treatment which has proven efficacy and lasting outcomes.’

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clinical presentation

The licence was based on a multi-centre clinical trial that showed excellent efficacy (complete clinical and histological remission of the disease of 58% at six weeks and 85% at 12 weeks compared to 0% on placebo; (p<0.001). • Jorveza achieved >90% histological remission in all three to 0% on placebo • Jorveza also achieved significantly higher reduction in blood eosinophil counts (-219 compared with -28 on placebo; p<0.001) • Jorveza was well tolerated with no serious AE’s or changes in morning serum cortisol, a marker of steroid side effects

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• Over 58% of patients on Jorveza had clinico-histological remission at six weeks • Jorveza achieved marked reduction in Eosinophilic Oesophagitis activity index fibrotic sub score (EEAI-fibrotic sub score) at six weeks • Jorveza led to quick onset of symptom resolution and

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sections of the oesophagus (proximal, mid and distal) compared

significantly more days with no dysphagia than placebo liment Pharmacol Ther 2016; 43(1): 3-15. Arias Á et al A Gastrointest Pharmacol Ther 2016; 7(2): 207-13. Ahmed M. World J Gastroenterology 2017; 152(5, Suppl.1): S865. Reed CC et al. 7 Gut 2015; 64(Suppl.1): A21. Osuoha G et al.

4 5 6

Gastro-Today_Half-Ad_Feb19.indd 1

15/01/2019 14:48:14

POSTERS

EFFECT OF TURMERIC ON THE FAECAL VOLA

Gaurav Rattan Vashisht, R

Introduction

Turmeric

Inflammatory bowel disease (IBD), amongst other gastrointestinal disease, affects the gut microbiome and metabolome. Curcumin, from turmeric, may be of benefit in some patients through action on the gut microbiome. Curcumin produces changes to bile acid secretion and has a variety of direct effects on bacteria. Faeces release faecal Volatile Organic Metabolites (VOMs),

Crohn’s Disease, UC & IBS

which partly reflect the gut microbiome. The aim of the study was to investigate the effects of

Healthy Individuals

turmeric on the VOMs in healthy individuals.

Effect on IBS & UC symptoms

Influence on Gut Flora

Methods 5 participants were enrolled in a before-during-after pilot study, in which they were asked to take a turmeric-free diet and then to consume 1.6g of turmeric daily for 5 days.

Possible Changes on Metabolome Figure 1 - Schematic justifying why the study was needed Key for Figure 1

Faecal samples were collected at baseline, after 5 days of turmeric ingestion, and again 5 days after this, and frozen immediately. What the current pilot study focused on looking for The samples were analysed by an investigator blinded using gas chromatography / mass spectrometry. Analytes were identified using AMDIS software and compared using Metaboanalyst software: ANOVA, PCA, PLS-DA, and Heatmap were employed

Existence of evidence base for a possible mechanism of action of turmeric on the metabolome of patients with GI disease.

The coloured boxes in Figures 2 and 3 indicate the relative concentrations of

corresponding metabolite in each of the comparison groups. B (before turmeric consumptio D (During turmeric consumption) and A (after turmeric consumption). Comparisons of faecal VOMs before, during and after turmeric ingestion were made using ANOVA, since there were more than two comparison groups.

Additionally, using unsupervised modelling software, PCA (Principal Component Analysis) and PLS-DA (Partial Least Squares - Discriminant Analysis) were used to investigate if any possible correlation existed between any of the comparison groups. PLS-DA best looks for separation between the comparison groups.

Previous research by Ahmed I et al. found a significant change in VOMs that are positively associated with specific GI diseases when compared to each other, and more importantly for this study, when compared to healthy controls.1,2

It was thought that turmeric may produce a significant shift in the levels of the VOMs away from that of diseased states, in healthy individuals. These compounds that were previously found to be associated with disease were looked at in a secondary analysis for evidence of shifts away from that of diseased states, in healthy individuals (Figure 3).

Butanoic acid, 3-methyl-, butyl ester 2-Heptanone, 5-methylAcetyl valeryl 4-Methylpentanoic acid Pentanoic acid Nonanal 1H-Pyrrole-2,5-dione, 3-ethyl-4-methylmethyl propanoate Pentanoic acid, methyl ester Butanoic acid 2-Nonanone 2-Heptanone Propanal, 3-(methylthio)Cyclohexanecarboxylic acid, methyl ester Propanoic acid

B D A

VIP scores Figure 2 – Variable importance projection (VIP) scores from compounds identified b PLS-DA.

GASTROENTEROLOGY TODAY - SPRING 2019

Selected compounds Box plots were generated from raw data for each of the compounds identified by the prior analysis described above. Kruskal-Wallis H test examined whether difference in abundance of each compound was statistically significant across comparison groups.

B D A

4-Methylpentanoic acid methyl propanoate Phellandrene Acetic acid

Participant Age 22

Ethnicity Chinese Medications and None dietary supplements Sensitivities? None Smoker? Yes Regularly consume No turmeric-containing foods

Arab

British

Sri Lankan

None

Multivitamin, None Propranolol (PRN)

None

No No

Lactose, Coffee No Yes – 5 grams per week

Table 1 - Demographics of the study participants

All compounds

Acetone Propanoic acid Methyl butanoate Nonanal Pentanoic acid, methyl ester Propyl propionate

VIP scores

Figure 3 – VIP scores from PLS-DA analysis with certain compounds excluded. T

compounds included were those that were previously found to be associated w

disease. This was done to see if there were shifts in concentration of VOMs away fro that of diseased states, in healthy individuals.

Acknowledgements The principal investigator was Gaurav R. Vashisht (GRV), under the supervision of Professor Chris S. Probert (CSP). GRV conceived, designed and performed the experiment. Miss Rachael Hough and Miss Lauren Lett helped with GC-MS ana BL, Ratcliffe NM, Probert CS. An Investigation of Fecal Volatile Organic Metabolites in Irritable Bowel Syndrome. PLoS One 2013;8(3). 2. Ahmed I, Greenwood R, Costello B, Ratcliffe N, Probert CS. Investigation of faecal volatile organic metabolites as novel dia Microbiol 2013;62(1):91-5. 4. Foligné B, Breton J, Mater D, Jan G. Tracking the microbiome functionality: focus on Propionibacterium species. Gut 2013;62(8):1227-8.

POSTERS

ATILE ORGANIC METABOLITES IN HEALTHY INDIVIDUALS

Rachael Hough, Lauren Lett, Chris Probert Results

No significant features were found using ANOVA. For most of the VOMs found between the comparison groups, p>0.05. PCA did not show separation by group (Figure 4). However, PLS-DA analysis (Figure 5) suggested separation, which is a promising result, given the small number of participants (n=5). Heat-map analysis did not show any pattern in the abundance of VOMs. Variable importance projection (VIP) scores showed a decrease in the abundance of propanoic acid and methyl propanoate in the intervention samples when compared to baseline and post-turmeric consumption. The box plots created from raw data in Figure 6 demonstrated lower median abundances of intervention samples as compared to comparison groups.

Classification of VOMs Carboxylic acids 4-Methylpentanoic acid Propanoic acid B D A

B D A

Cyclic Monoterpenes Alpha-Phellandrene Esters Methyl butanoate Methyl propanoate Propyl propionate

Figure 4 - PCA score plot not showing a clear

between the comparison the groups for all VOMs.

Table 2 - VOMs that appeared to have decreased during turmeric ingestion, compared to before or after.

Conclusion metabolism. The VOMs methyl butanoate, 4-Methylpentanoic acid and methyl propanoate may correlate with a change in abundance or activity of Bacteroides spp. Methyl butanoate also appears to relate to the presence of Faecalibacterium prausnitzii. (Table 3) Studies in patients with IBD, IBS (irritable bowel syndrome) and NAFLD (non-alcoholic fatty liver disease) are warranted. Turmeric appears to change VOMs related to Propionibacterium and Bacteroides spp., and more work is needed to investigate the effects on the microbiome.

4.5

*Abundance in arbitrary units (x106)

100 90 80 70 60 50 40 30 20 10

4 3.5 3 2.5 2 1.5 1 0.5 0

Before

During

Before

After

During

After

Max Outlier

Figure 6 - The box plots above demonstrated the changes in abundance of propanoic acid (left) and methyl proprionate (right) , amongst the comparison groups: “Before” turmeric consumption, “During” turmeric consumption and “After” turmeric consumption.

Bacterial species

Effect on disease

Bacteroides spp.

NAFLD: The negative impact of turmeric had on Bacteroides spp. indicates that turmeric consumption may not be beneficial in patients with NAFLD. This is because it caused the SCFA methyl propanoate to decrease. (SCFAs have been purported to have beneficial effects). IBS: Turmeric consumption may be responsible for decreased activity or abundance of Veillonella and Lactobacillus bacteria. This is likely to be a positive effect of turmeric, as these

Lactobacillus

bacteria are implicated in IBS pathogenesis.

Faecalibacterium

Crohn's disease: In Crohn's disease, turmeric may cause a negative effect. This is because turmeric could further decrease levels or activity of Faecalibacterium prausnitzii, which is

prausnitzii

already lowered because of Crohn's disease.3

Propionibacterium

IBD: Propionibacterium spp. are possibly reduced by turmeric consumption. This may be seen as a positive effect. Propionibacterium isolated in the digestive tract include opportunistic

spp.

pathogens, some of which that are not as innocuous as the Propionibacteria strains found in dairy products.4 The opportunistic strains of Propionibacteria have potential to induce pro-

Two

Veillonella and

inflammatory molecules such as: interleukin (IL)-8, IL-12 and interferon γ.4 These molecules are unwanted in the setting of IBD. Therefore, turmeric may be beneficial at reducing inflammation, through the possible reduction of Propionibacteria. In healthy participants, Propionibacteria are not part of the main microbiota, so a reduction in their activity or abundance may be seen as beneficial.4 Table 3 - The bacterial species whose activity or abundance in the gut has possibly been reduced by turmeric consumption, and the effect this has various diseases. Particular emphasis

GASTROENTEROLOGY TODAY - SPRING 2019

with

VOMs.

This pilot study illustrated that six VOMs appear to become less abundant when turmeric is consumed (Table 2). The VOMs propanoic acid and methyl propanoate appear related to Propionibacterium

The

Figure 5 – PLS-DA score plot suggesting separation

*Abundance in arbitrary units (x106)

the

on),

correlation between the comparison groups for all

should be given to Propionibacterium spp., where two associated compounds were reduced on turmeric consumption.

alysis of faecal samples. CSP supervised of data analysis and interpretation. CSP contributed to the reagents/materials/analysis tools. GRV wrote the paper. There are no financial conflicts of interest to disclose. References 1. Ahmed I, Greenwood R, Costello agnostic biomarkers in inflammatory bowel disease. Aliment Pharmacol Ther 2016;43(5):596-611. 3. Galecka M, Szachta P, Bartnicka A, Lykowska-Szuber L, Eder P, Schwiertz A. Faecalibacterium prausnitzii and Crohn's disease - is there any connection? Pol J

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