Sign 68 Full

8/3/2019 Sign 68 Full

http://slidepdf.com/reader/full/sign-68-full 1/30

Scottish Intercollegiate Guidelines Network

Dyspepsia

A national clinical guideline

1 Introduction 1

2 Dyspepsia in the community 5

3 Management of uncomplicated dyspepsia 8

4 H. pylori tests 10

5 Management of functional dyspepsia 12

6 Implementation and audit 17

7 Patient information 19

8 Development of the guideline 20

68

8/3/2019 Sign 68 Full


KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS

LEVELS OF EVIDENCE

1++ High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs),or RCTs with a very low risk of bias

1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a lowrisk of bias

1 - Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2

++

High quality systematic reviews of case control or cohort studiesHigh quality case control or cohort studies with a very low risk of confounding or biasand a high probability that the relationship is causal

2+ Well-conducted case control or cohort studies with a low risk of confounding or biasand a moderate probability that the relationship is causal

2 - Case control or cohort studies with a high risk of confounding or biasand a significant risk that the relationship is not causal

3 Non-analytic studies, e.g. case reports, case series

4 Expert opinion

GRADES OF RECOMMENDATION

Note: The grade of recommendation relates to the strength of the evidence on which therecommendation is based. It does not reflect the clinical importance of therecommendation.

A At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++

and directly applicable to the target population ; or

A body of evidence consisting principally of studies rated as 1+, directly applicable tothe target population, and demonstrating overall consistency of results

B A body of evidence including studies rated as 2++, directly applicable to the targetpopulation, and demonstrating overall consistency of results ; or

Extrapolated evidence from studies rated as 1++ or 1+

C A body of evidence including studies rated as 2+, directly applicable to the targetpopulation and demonstrating overall consistency of results ; or

Extrapolated evidence from studies rated as 2++

D Evidence level 3 or 4 ; or

8/3/2019 Sign 68 Full


1 INTRODUCTION

1 Introduction1.1 BACKGROUND

This guideline builds on the work already undertaken by SIGN on dyspepsia and incorporatesnew evidence in controversial areas. In August 1996, SIGN published a national clinical guidelineon Helicobacter pylori (H. pylori) eradication therapy in dyspeptic disease.1 A single sheet updateof this guideline was issued in October 1999.2 Both publications provided evidence-basedrecommendations on which patients with H. pylori should receive eradication therapy and which

eradication regimens to use. These SIGN Guidelines on H. pylori eradication therapy raised theissue of how H. pylori infection may alter the way in which we investigate patients presentingwith dyspepsia.

This guideline specifically addresses the investigation and management of dyspepsia and updatesthe evidence base for the key indications for H. pylori eradication in duodenal ulcer, gastric ulcerand low grade gastric MALT lymphoma (see Annex 1).

1.2 THE NEED FOR A GUIDELINE

Upper gastrointestinal symptoms affect up to 40% of adults in any one year.3-5 Some 50% of sufferers self-medicate, perhaps with advice from community pharmacists, with only about onein four sufferers consulting their general practitioner.3-5

Scottish prescribing data revealed a 27% increase in the number of prescriptions for ulcer healingdrugs between 1996 and 2001.6 Despite the significant increase in the volume of prescribing, thecost in absolute terms has reduced, from £72.5 m per annum to £71 m over the same period.This is partly due to price reductions of Proton Pump Inhibitors (PPIs) and the generic tariff

prices for those H2 receptor antagonists (H2RA) available on the Scottish Drug Tariff, and partlydue to increasing use of maintenance doses of PPIs. Upper gastrointestinal symptoms nonethelessimpose a substantial burden on the Scottish healthcare system3,7 as well as causing significantquality of life impairment for the individuals who suffer them.8,9

1.3 TERMINOLOGY

1.3.1 DYSPEPSIA

The term dyspepsia has been used inconsistently by healthcare professionals to describe differingpatterns of upper gastrointestinal (GI) symptoms. The consequent lack of comparability betweenpublished studies of dyspepsia has been a major barrier to resolving clinical uncertainty aboutbest practice for investigation and treatment of patients. Clarity about the terminology is thus anessential preliminary to formulating an up to date guideline on clinical practice. Dyspepsiadenotes symptoms and is not itself a disease. The guideline development group accepted theRome II definition:10 Dyspepsia refers to pain or discomfort centred in the upper abdomen

8/3/2019 Sign 68 Full


DYSPEPSIA

Patients with functional dyspepsia who identify pain as their predominant symptom may be said

to have ulcer-like dyspepsia whereas patients with discomfort as their predominant symptommay be said to have dysmotility-like dyspepsia.10

1.3.2 HEARTBURN, DYSPEPSIA AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)

Confusion often accompanies consideration of the relationship between heartburn, dyspepsiaand GORD. A first step towards minimising this confusion is to recognise that heartburn anddyspepsia describe symptoms, whereas GORD is a collective term embracing all diseases causedby gastro-oesophageal reflux.

Retrosternal heartburn, the classical symptom of GORD, is not included within the Rome IIdefinition of dyspepsia because it is not an upper abdominal symptom. A diagnosis of GORDmay be made with high confidence for patients who describe retrosternal heartburn and/or acidregurgitation as their principal complaints. This diagnosis is less certain when pain or discomfortcentred in the upper abdomen (Rome II dyspepsia) is accompanied by heartburn as a secondary,subordinate symptom, hence the emphasis given to the predominant symptom as the basis fordiagnosis.

Not all patients with GORD present with classical heartburn. A minority of patients describe

upper abdominal pain or discomfort (Rome II dyspepsia) as their principal symptom: otherrecognised �atypical� presentations of GORD include asthma and non-cardiac chest pain.

Distinguishing dyspepsia from heartburn potentially allows appropriate diagnostic significanceto be attached to each of these symptoms. Recognition that heartburn is the classical, but not theonly, clinical presentation of GORD serves as a reminder that heartburn and GORD should notbe equated.

þ A diagnosis of gastro-oesophageal reflux disease (GORD) is likely if retrosternal heartburnand acid regurgitation are a patient�s principal complaints. The term �reflux-like dyspepsia�

is no longer recommended to describe these symptoms.

1.3.3 OESOPHAGEAL AND GASTRIC CANCER

A minority of patients with dyspepsia will have major organic pathology, e.g oesophageal orgastric cancer. This guideline highlights the alarm features (see sections 2.2 and 2.4) that wouldidentify patients who require early referral to a hospital specialist.

1.4 REMIT OF THE GUIDELINE

This guideline provides recommendations based on current evidence for best practice in themanagement of dyspepsia in adults. It includes guidance on investigation and treatment of dyspepsia, but does not specifically address the clinical management of:

n Diagnosed gastro-oesophageal reflux disease (GORD) (this may be addressed by a futureSIGN guideline)

8/3/2019 Sign 68 Full


methods of care or excluding other acceptable methods of care aimed at the same results. The

ultimate judgement regarding a particular clinical procedure or treatment plan must be made bythe doctor, following discussion of the options with the patient, in light of the diagnostic andtreatment choices available. However, it is advised that significant departures from the nationalguideline or any local guidelines derived from it should be fully documented in the patient�scase notes at the time the relevant decision is taken.

1.6 REVIEW AND UPDATING

This guideline will be issued in 2003 and will be considered for review as new evidence becomes

available. Any updates to the guideline will be noted on the SIGN website: www.sign.ac.uk

1 INTRODUCTION

8/3/2019 Sign 68 Full


DYSPEPSIA

DYSPEPSIA*

Persistent / recurrent symptoms

Persistent / recurrent symptomsdespite conf irmed eradication

Hp test Hp test -ve

PREDOMINANTHEARTBURN

MANAGEAS GORD

Hp test + ve

Eradicate Hp

ALARM FEATURES

Dysphagia Evidence of GI blood loss Persistent vomiting

Unexplained weight loss Upper abdominal mass

Consider

Heart

Liv

er Gall bladder Pancreas

Bowel NSAIDs etc

UNCOMPLICATED DYSPEPSIA

Consider Lif estyle Antacids / H2RA

REFER TO

HOSPITAL

SPECIALIST

"INDIGESTION"

Yes

Yes

No

No

Figure 1

8/3/2019 Sign 68 Full


2 Dyspepsia in the community

People with dyspepsia may choose several routes for the initial management of the condition.Some people purchase antacids or H2RA medicines over the counter, some consult with acommunity pharmacist and others will consult their general practitioner. Figure 1 on page 4describes an evidence-based approach to investigation and management.

2.1 THE ROLE OF THE COMMUNITY PHARMACIST

The UK market for over the counter indigestion remedies was £88.5m in 1999 and £93.7m in2000.11 In the UK, antacids are categorised under the Medicines Act, Section 3 1978, as generalsales list (GSL) items and may be bought at a variety of sales outlets such as supermarkets, petrolstations and corner shops without the supervision of a pharmacist. Antacids may also be purchasedfrom pharmacies. H2RAs are categorised as either GSL for 6 to 12 tablets of ranitidine or aspharmacy supervised sale (P), for larger quantities of ranitidine or other H2RAs. The dose of overthe counter H2RA is usually 50% of the standard prescribed maintenance dose and the quantityis limited to 24 tablets in a pack. Users are advised they should not be taken for prolonged

periods without seeking medical advice.

Pharmacists are well placed to provide an early intervention for people suffering from symptomsof dyspepsia. It has been demonstrated that advice on self-medication and counselling bypharmacists has a measurable impact on health-related quality of life and that patients value theinformation that pharmacists provide.12 Patients advised to visit their general practitioner (GP) bytheir pharmacist may not present to their GP. This could be important if their symptoms includealarm features that may be suggestive of a more serious pathology.13

D Community pharmacists should advise patients suffering from dyspepsia associated withalarm symptoms to consult their general practitioner (see section 2.4).

2.2 PRESENTATION IN GENERAL PRACTICE

The general practitioner, faced with the patient complaining of �indigestion� will consider allpossible sources including the oesophagus, stomach, heart, liver, gall bladder, pancreas, bowel,NSAIDs and other drugs.

Alarm features such as dysphagia, evidence of GI blood loss, persistent vomiting, unexplainedsignificant weight loss or an upper abdominal mass should be identified (see section 2.4). Patientswith these findings merit early referral to a hospital specialist. The management strategy foruncomplicated dyspepsia given in this guideline should only be used if pathology outwith thestomach and proximal duodenum is thought unlikely and alarm features are not present. Itshould again be emphasised that this guideline does not address dyspepsia associated withNSAID use.

2 DYSPEPSIA IN THE COMMUNITY

2+

Extrapolated

from studiesrated 2+

8/3/2019 Sign 68 Full


DYSPEPSIA

Computerised models have been developed using multiple clinical and demographic criteria to

try to identify patients at low risk of organic dyspepsia and hence improve the likelihood of anaccurate diagnosis.16,17 Computerised models are rarely validated and cannot therefore be generallyrecommended.16

C Symptom assessment cannot be relied upon to make a diagnosis of the cause of dyspepsia.

2.4 ALARM FEATURES AND RISK OF CANCER

Many guidelines recommend that alarm features such as dysphagia, recurrent vomiting, significant

unintentional weight loss, anaemia from gastrointestinal haemorrhage or upper abdominal mass,are used as predictors for major pathology (eg ulcer with complications or oesophageal cancer) inpatients with dyspepsia. 18,19 They further recommend that patients of any age with these featuresshould have early investigation.18,19 These recommendations tend to be based on expert opinionrather than published evidence.18,19

The evidence concerning alarm features such as dysphagia, recurrent vomiting, significantunintentional weight loss, anaemia from gastrointestinal haemorrhage or upper abdominal massdoes not allow clear conclusions. In some studies 20-23 alarm features are seen to be predictive of

major pathology, but in others this association is not found.24

A recent American multicentredatabase study of 3815 patients having first endoscopy for dyspepsia, showed that male sex, ageover 45 years and anaemia were significant but weak predictors for major upper GI pathology.25

In this study, weight loss and dysphagia were not found to be significant predictors. It wasdemonstrated that age and alarm features are not effective predictors of endoscopic findingsamong patients with dyspepsia and that better clinical prediction strategies are required.

Several cohort studies show that up to 95% of younger patients (age ranges used in studies varybetween under 45 years to under 55 years) with upper GI cancer have more than one alarmfeature. 20,21,25,26 The Scottish Audit of Gastric and Oesophageal Cancer (SAGOC) data show that9% of patients with upper GI cancer in Scotland are under 55 years of age and 93% of them havean alarm feature at the time of presentation.27

In the dyspeptic population, some alarm features (age over 45 years, anaemia, male sex) are weakpredictors for upper GI cancer.25However, in populations of patients with dyspepsia and upperGI cancer, alarm features are almost always present.20,21

B Patients with dyspepsia and alarm features should be referred to a hospital specialist forassessment.

2.4.1 AGE AND GASTRIC CANCER

In 1998 both the American Gastroenterological Association18 and a working party for the WorldCongress of Gastroenterology advised that patients over 45 and 50 years of age respectivelypresenting with new onset uncomplicated dyspepsia should undergo early upper GI endoscopy.28

This recommendation was not evidence-based but arose from a perception that non-invasive

4

2-

2++

2++2++

4

2++

8/3/2019 Sign 68 Full


2.4.2 ENDOSCOPY VERSUS BARIUM MEAL FOR PATIENTS WITH ALARM FEATURES

Endoscopy is more sensitive than barium meal at detecting early curable gastric cancer and isalso more likely to detect gastric and duodenal erosions.30,31 Any lesions seen can also be biopsiedimmediately. A well conducted barium meal is a useful investigation which will detect mostserious disease in the upper GI tract32 but it does involve a radiation dose (typical effective dose2mSv equivalent to 11 months of background radiation).33 This is particularly relevant now thatthe European Union regulations governing the exposure of patients to medical radiation are inforce.34

C Upper GI endoscopy is the investigation of choice when further evaluation is warranted

and should be widely available.

þ Barium meal studies are appropriate where the local endoscopy services are unavailableor for patients who cannot tolerate endoscopy.

2 DYSPEPSIA IN THE COMMUNITY

2+

4

8/3/2019 Sign 68 Full


DYSPEPSIA

3 Management of uncomplicated dyspepsia

Uncomplicated dyspepsia refers to patients whose dyspepsia is not accompanied by alarm featuresor associated with NSAID usage. The traditional management of patients in primary care hasbeen to consider the role of lifestyle, antacids and H 2RAs. There are a number of possibleapproaches to the management of patients with persisting or recurrent symptoms (see Figure 1, page 4). Some of these approaches incorporate the role of H. pylori infection in the aetiology of ulcer disease. Most studies of these approaches have involved patients of less than 55 years of age.

3.1 PATIENTS LESS THAN 55 YEARS OF AGE

Acid suppression therapy

This has the disadvantage of depriving those with underlying ulcer disease from being cured byeradication of H. pylori infection.35-37

Early endoscopy

Studies show that early upper GI endoscopy may be more effective than empirical prescribingbut the benefit is small, not significant and unlikely to be cost-effective.38-40

H. pylori �test and endoscope�

This strategy involves performing a non-invasive H. pylori test and performing endoscopies onlyon those patients with a positive result. This approach is no more effective, or less costly, thanselective endoscopy at the general practitioner�s discretion.38,40

H. pylori �test and treat�

This strategy involves performing a non-invasive H. pylori test, eradicating the infection in allthose testing positive and providing symptomatic treatment for those who test negative. Fiverandomised trials have compared the non-invasive H. pylori test and treat strategy with upper GIendoscopy. One of the trials randomised those with a positive non-invasive H. pylori test toendoscopy versus H. pylori eradication therapy without further investigation 41 and another trialrandomised patients with a negative non-invasive H. pylori test to endoscopy versus symptomatictreatment.42 A further three trials randomised patients at the point of presentation to endoscopyversus non-invasive H. pylori testing.43-45Each of the five trials came to the same general conclusion,

that non-invasive H. pylori testing was as effective as endoscopy in determining the managementof dyspepsia.41-45

The above strategy involves eradicating H. pylori infection in dyspeptic patients without underlyingulcer disease. There may be advantages and disadvantages related to this.46,47

Advantages include: 46,47

i b fi f di i h i f i i ll b f i i h

1+

1++

8/3/2019 Sign 68 Full


It is recognised that the balance of advantages over disadvantages for the H. pylori test and treat

strategy will be less in populations with a low prevalence of H. pylori infection and relatedulcer disease. The prevalence of H. pylori infection in the Scottish population with dyspepsia isapproximately 40% at present and more than 20% of these patients have underlying ulcers.45Theprevalence of H. pylori infection within any population increases with age and with lower socio-economic status.50

The H. pylori test and treat strategy is as effective and safe as endoscopy in determining themanagement of patients less than 55 years old with uncomplicated dyspepsia. In view of thefact that the H. pylori test and treat strategy is both non-invasive and cheaper than upper GIendoscopy,38,39,41-49 it is considered to be the preferred strategy. Facilities for non-invasive H. pylori testing should therefore be widely available.

A A non-invasive H. pylori test and treat strategy is as effective as endoscopy in the initialmanagement of patients with uncomplicated dyspepsia who are less than 55 years old.

3.2 PATIENTS OVER 55 YEARS OLD

Current guidelines advise that older patients (age ranges used in studies vary between over 45 to

over 55 years) with uncomplicated dyspepsia should be investigated using early upper GIendoscopy.18,19,28,51,52 The phrase �recent onset� is also frequently used to indicate a need for moreurgent investigation of dyspepsia. An examination of the literature does not produce evidence tosupport these claims.

3.2.1 MANAGEMENT

This guideline has cited substantial evidence supporting the use of non-invasive H. pylori testingin place of upper GI endoscopy in determining the management of patients less than 55 years oldpresenting with uncomplicated dyspepsia (see section 3.1). The question as to whether this

recommendation can be extrapolated to include patients presenting with uncomplicated dyspepsiawho are more than 55 years old has not yet been directly addressed by an RCT. There are,however, recent studies comparing the outcome of non-invasive management versus early upperGI endoscopy for this group of patients where no upper age limit was defined for inclusion in thestudy.

An RCT studied 500 Danish patients between the age of 18 and 88 years with recent onsetuncomplicated dyspepsia with or without concomitant reflux symptoms. The patients wererandomised to either H. pylori test and treat policy or early endoscopy and followed up for one

year. The test and treat policy was as efficient and as safe as prompt endoscopy.43

A Canadian general practice controlled trial randomised 294 H. pylori positive patients with atleast three months of uninvestigated dyspepsia (age range 18 to 82 years) to either H. pylorieradication therapy or omeprazole 20 mg for seven days.53 The test and treat strategy showedsignificant symptomatic benefit after 12 months follow-up. Two patients died of cancer duringthe study, one from a brain tumour and one from inoperable oesophageal cancer that presented

3 MANAGEMENT OF UNCOMPLICATED DYSPEPSIA

1++

1+

1+

8/3/2019 Sign 68 Full


DYSPEPSIA

4 H. pylori tests

Two aspects about diagnostic testing for H. pylori must be considered to evaluate its accuracy(that is, the ability of a diagnostic test to produce correct test results). The first is how well thetests detect H. pylori infection in patients (sensitivity) and the second is how well the testcorrectly identifies patients who do not have the infection (specificity). The selection of theappropriate test for H. pylori infection should also be based on the prevalence of H. pyloriinfection in the community (see Annex 2). The major groups of non-invasive tests are breathtests, serological tests and faecal antigen tests.

4.1 BREATH TESTS

Since their introduction, both 13C and 14C urea breath tests (CUBTs) have been used widely inpatients both before and after H. pylori eradication therapy.55 An RCT has shown that, comparedto an accepted gold standard, accuracy was 94.8% before antimicrobial therapy and 95.4%afterwards.56 False negative results may occur and CUBT should not be performed within twoweeks of proton pump inhibitor (PPI) or within four weeks of antibiotic therapy.57

4.2 SEROLOGICAL TESTS

4.2.1 HOSPITAL BASED TESTS

Enzyme-linked immunosorbent assays (ELISAs) are the most commonly used serological methodfor the detection of H. pylori infection, and a large number of commercial ELISA kits are nowavailable. Evaluation of test kits is usually made by using an appropriate �gold standard� consistingof a combination of culture, histology, CLO-test and breath testing as no technique is 100%

sensitive or specific for detecting H. pylori infection. Studies of the sensitivity and specificity of these tests have produced inconsistent results. One meta-analysis of 21 studies showed sensitivityand specificity of 85% and 79% respectively and concluded that there is little evidence tosuggest that any of the common commercial serological kits is more accurate than another andthat the overall accuracy of these kits may not be adequate for clinical decision-making in allpatient groups. 58

The Medical Devices Agency also evaluated a large number of ELISA tests.59 588 samples of serawere evaluated with 16 different tests. The overall accuracy of the assays averaged 78% (range

68-82%) for all sera. A further meta-analysis gave broadly similar results but reached no conclusionsas to whether the use of kits was appropriate.60

A large review, using different methodology, contradicted these results. In a comparison of 36different commercially available H. pylori serology kits on 26,812 patients the median sensitivityand specificity were 92% and 83%.61 Kits measuring IgA, IgG, and IgM simultaneously or IgAalone did not perform as well as those measuring only IgG antibodies. This review concluded

1++

1+

2+

8/3/2019 Sign 68 Full


4.3 FAECAL ANTIGEN TESTS

Enzymatic immunoassays that detect the H. pylori antigen in stool specimens are available. Alarge number of patients have been evaluated using the stool antigen test for the initial diagnosisof H. pylori infection and the mean sensitivity and specificity has been calculated at 93.1% and92.8% respectively.62 Caution is needed following eradication therapy as omeprazole significantlyreduces faecal antigen values, resulting in a decreased accuracy.65,66

4.4 CHOOSING A TEST

4.4.1 PRE-TREATMENT DIAGNOSISIn the primary care setting, the ELISA (hospital based serology) and CUBT have been shown to beequally effective in excluding the diagnosis of infection with H. pylori in patients who have haddyspeptic symptoms for at least two weeks.67 Whole blood tests produced inferior results.67 Amulticentre study suggests that the faecal antigen test is comparable with the CUBT in the initialdetection of H. pylori infection.68

In trials that compare the use of endoscopy with H. pylori test and treat, some have used CUBTand others have used serology testing.43,45 Outcomes from both types of test have been similar. In

clinical practice therefore, the difference in accuracy between the two tests may not besignificant.43,45

4.4.2 POST-ERADICATION TESTING

CUBT has been shown to be effective in detecting eradication of H. pylori infection. Sevenstudies using CUBT alone as a comparison found the sensitivity and specificity of both faecalantigen testing and CUBT was approximately 90%. There has however been some variability inthe results of the faecal antigen test in the post-therapy setting so at present faecal antigen testing

is not comparable to CUBT in the post-therapy setting.68

Serology may be used for monitoring the efficacy of H. pylori eradication therapy but both pre-and post-treatment samples must be analysed simultaneously and it is necessary to wait a minimumof three months following eradication therapy before repeating the test.69

B The CUBT or faecal antigen tests are recommended for the pre-treatment diagnosis of H. pylori infection in the community. Less accurate, hospital-based serology tests have aplace within the non-invasive test and treat strategy.

B CUBT is the recommended test to determine whether H. pylori has been successfullyeradicated.

þ The CUBT should not be performed within two weeks of proton pump inhibitor therapyor within four weeks of antibiotic therapy as false negative results may occur.

4 H.PYLORI TESTS

2+

2++

2++

8/3/2019 Sign 68 Full


DYSPEPSIA

5 Management of functional dyspepsia

5.1 INTRODUCTION

Functional dyspepsia is the recommended term to denote dyspepsia for which no causal organicdisease has been identified (see section 1.3). As it is a diagnosis of exclusion, clinical judgementmust be exercised in the case of each patient to decide how much investigation is appropriatebefore the diagnosis may reasonably be applied. However, when taking these decisions, physiciansshould bear in mind that functional dyspepsia is more common than dyspepsia caused by underlying

organic disease and that for most patients under 55 years of age, invasive investigation is notnecessary before a working diagnosis of functional dyspepsia may be made.

Having made a diagnosis of functional dyspepsia, the clinician will wish to consider treatmentoptions. Part of this consideration requires assessment of what has triggered the patient�sconsultation: consultation with dyspepsia is more probable if the patient is anxious, depressed,stressed, has severe symptoms or is worried that the symptoms are signals of a life threateningillness.70,71 Such concerns, if present, need to be addressed.

Not all patients with functional dyspepsia seek active treatment: for some, it may be sufficient to

explain the condition and give reassurance that no serious disease has been found. For others,however, treatment may be warranted. Clinicians should remember that although by definitionthe causes and mechanisms responsible for functional dyspepsia symptoms are unknown, thereis reason to believe that several different derangements of upper GI motor and sensory functionmay be implicated. This raises the possibility that symptom alleviation will need differenttreatments in different patients. Inevitably, clinical trials that have considered functional dyspepsiaas a single entity and assessed the effect of one therapy do not address this possibility.

þ A working diagnosis of functional dyspepsia is likely to be appropriate for most patients

with dyspepsia who have no alarm features and in whom initial investigations are negative.Repeated or increasingly invasive investigation in pursuit of an organic cause for thesymptoms may be both futile and counter-productive.

5.2 LIFESTYLE ADVICE

Eleven observational studies and surveys which consider functional dyspepsia and lifestyle factorswere identified. Most of the published literature is based upon patients� self-reported experiences,

and is subject to the methodological criticisms associated with this type of data collection. Onesurvey indicated that poor diet, stress and caffeine are perceived as the most common causes of GI symptoms.72 Another survey found that 80% of dyspeptic patients reported that avoidance of specific foods helped relieve dyspeptic symptoms.73 Irregular eating patterns have been identifiedin functional dyspepsia, and this has been linked to stress, but causal effect is not clear. 73,74 Awide variety of food intolerances have been reported,75 many of which patients are able toidentify and self treat without recourse to professional advice Caffeine alcohol and smoking

8/3/2019 Sign 68 Full


5.3 PSYCHOLOGICAL TREATMENTS

The correlation of psychosocial problems with functional dyspepsia suggests that psychosocialinterventions may have a role in treatment.81 At the present time however there is no stronggeneralisable evidence on the benefit of this kind of intervention.82

It is not possible to make a recommendation on the role of psychosocial interventions in themanagement of functional dyspepsia.

5.4 PHARMACOLOGICAL TREATMENTS

5.4.1 INTRODUCTION

Not all patients with functional dyspepsia require drug treatment. However, when prescriptionof medication is being contemplated, clinicians should appreciate that in functional dyspepsia,as in all other functional GI disorders, there is a substantial placebo response to therapy thatconstrains the interpretation of apparent treatment effectiveness in individual patients. No drugtherapies have been found to have a high success rate in the treatment of functional dyspepsiathough it should also be acknowledged that there is no scientific basis for supposing that allpatients with functional dyspepsia should respond to the same pharmacological approach.

Heterogeneity of presenting symptoms is evident in functional dyspepsia, heterogeneity of underlying mechanisms is suspected and there is some evidence suggesting different therapiesmay be effective for different patients. Conclusive evidence of this is lacking, however. Theavailable information concerning drug therapy for functional dyspepsia all relates to relativelyshort term treatment periods and consequently drug treatment should usually be given on a shortterm basis only.

þ Medication is not necessary for all patients with functional dyspepsia. When medicationis given, short term treatment, intermittent if necessary, is likely to be more appropriate

than long term continuous therapy.

5.4.2 H. pylori ERADICATION

Four placebo controlled double blind RCTs compared effective eradication regimens to treatmentregimens ineffective against H. pylori in patients with functional dyspepsia.83-86 All four trialsassessed symptoms using validated symptom scores at 12 months and excluded patients withconfirmed peptic ulcer disease or oesophagitis at time of enrolment. Three of the four studiesrecruited patients with predominant symptoms of upper abdominal pain or discomfort (ROME II

definition10).83,84,86 One study also included patients with predominant symptoms of heartburn,and this was the only trial to demonstrate a significant benefit for H. pylori.85 A significantbenefit remained after heartburn predominant patients were excluded (23% response comparedto 10% in control group; p=0.02). This study was conducted in Glasgow and may therefore bemost relevant to the Scottish population.

Three meta-analyses on the effect of H. pylori eradication on functional dyspepsia have differed

5 MANAGEMENT OF FUNCTIONAL DYSPEPSIA

8/3/2019 Sign 68 Full


DYSPEPSIA

Overall because about 50% of patients with functional dyspepsia will be positive for H. pylori,eradication treatment will be symptomatically beneficial for slightly less than 5% of all functionaldyspepsia patients.

A H. pylori eradication therapy should be considered in the management of functionaldyspepsia.

5.4.3 ACID SUPPRESSION

The true benefit of acid suppression therapy in functional dyspepsia can be difficult to quantifyfor the following reasons:

n few trials of medication have defined functional dyspepsia according to the Rome II definition10

and excluded patients with predominant symptoms of acid reflux

n there is a high placebo response to treatment. 91

Acid suppression therapy can be separated into histamine receptor antagonists (H2RAs) and protonpump inhibitors (PPIs) and the results of treatment with either in functional dyspepsia are broadlysimilar.

One high quality RCT has shown a significant benefit from omeprazole over placebo of 10%

(38% compared with 28%).91This benefit increased in patient groups who had coexistent heartburnor epigastric pain, while no benefit was obvious in the patients with early satiety and nausea. Asimilar beneficial effect was demonstrated with H2RAs in patients with epigastric pain in trialsusing cimetidine 92 and ranitidine.93 There are no meaningful trials comparing the effects of PPIsand H2RAs.

Response to treatment has been associated with decreased health care costs and an improvementin health related quality of life. It has been suggested that patients who are more likely to gainlonger term benefit may have an identifiable response after only one week of treatment.94,95

A small number of patients with functional dyspepsia (10%) may benefit from acid suppressiontherapy. A response is more likely in those with co-existent heartburn.

B A trial of acid suppression therapy may be considered in the management of functionaldyspepsia.

5.4.4 ANTACIDS

No evidence was identified on the efficacy of antacids in the management of functional dyspepsia.

5.4.5 PROKINETICS

Domperidone or metoclopramide are the prokinetic drugs still prescribed for patients withfunctional dyspepsia. They have different pharmacological properties from cisapride, the licencefor which has been suspended in the UK.

Four meta analyses of RCTs have explored the role of prokinetic pharmacological therapies in

1+

1+

1++

1+

8/3/2019 Sign 68 Full


5.4.6 CYTOPROTECTIVES

Cytoprotective agents include chelates and complexes, such as bismuth chelate and sucralfateand the prostaglandin analogue, misoprostol. Sucralfate acts by protecting the gastric mucosa,misoprostol has both antisecretory and protective properties.

n Chelates and complexes

Three RCTs were identified however only one study was considered methodologically sound andthis study did not include a placebo group.100The two methodologically poor studies testing theefficacy of sucralfate produced conflicting results.101,102 One study showed no effect againstplacebo101 whilst the other was suggestive of benefit but no placebo group was included in this

study.102

n Prostaglandin analogues

One study found no difference in efficacy between misoprostol and placebo but did identifyincreased side effects in the misoprostol treatment group.103

It is not possible to make a recommendation on the role of cytoprotectives in the managementof functional dyspepsia.

5.4.7 ANTIDEPRESSANTS

A useful role for antidepressants in the management of idiopathic pain syndromes is often assumed.There is some evidence for the role of antidepressants in functional bowel disorders, but no clearevidence of benefit in functional dyspepsia.104-106

It is not possible to make a recommendation on the role of antidepressants in the managementof functional dyspepsia.

5.5 INFORMING PATIENTS

When a diagnosis of functional dyspepsia has been made, it may be helpful to explain to patientsthat:

n No disease or abnormality has been found and this should be taken as reassuring.

n Functional dyspepsia is very common and is not itself serious, though the discomfort, pain,distension and fullness which are perfectly genuine, are often unpleasant and bothersome.

n The definitive causes of functional dyspepsia are not known. It is known that, when comparedwith asymptomatic individuals, the stomach in many patients with functional dyspepsia

empties more slowly after meals. There is also evidence of heightened visceral sensation inmany functional dyspepsia patients who experience discomfort when the stomach is distendedto a degree that does not cause discomfort in healthy subjects.

n Functional dyspepsia is not a condition caused by gastric hypersecretion: acid secretion isusually normal.

n Functional dyspepsia is not usually caused by stress, anxiety or depression but these factors

5 MANAGEMENT OF FUNCTIONAL DYSPEPSIA

1-

8/3/2019 Sign 68 Full


DYSPEPSIA

5.6 PROGNOSIS IN FUNCTIONAL DYSPEPSIA

Little information is available that describes the long term outcome of patients with functionaldyspepsia in the United Kingdom. In a study of Swedish patients with functional dyspepsia,about two thirds still had dyspeptic symptoms after ten years of follow up.107 Many of them hadundergone repeat GI investigations during the ten years, though new organic disease was rarelyfound. In common with other studies108,109 many of these patients with functional dyspepsiaexhibited symptoms that overlapped with those of irritable bowel syndrome. In a small proportionof patients, symptom profiles may actually change with time from the one condition to theother.110

8/3/2019 Sign 68 Full


6 Implementation and audit

6.1 LOCAL IMPLEMENTATION

Implementation of national clinical guidelines is the responsibility of local NHS organisationsand is an essential part of clinical governance. It is acknowledged that not every guideline can beimplemented immediately on publication, but mechanisms should be in place to ensure that thecare provided is reviewed against the guideline recommendations and the reasons for any differencesassessed and, where appropriate, addressed. These discussions should involve both clinical staff

and management. Local arrangements may then be made to implement the national guideline inindividual hospitals, units and practices, and to monitor compliance. This may be done by avariety of means including patient-specific reminders, continuing education and training, andclinical audit.

6.2 KEY POINTS FOR AUDIT

In order for the audit of this guideline to be efficient the information used should be derivedfrom routinely collected data. It is recognised that due to gaps in the data available there may be

difficulties doing this. It is recommended that the national systems currently in place, such asthe Scottish Clinical Information Management Programme (http://www.ceppc.org/scimp/), beused to ensure appropriate diagnostic codes for functional dyspepsia, investigations and treatment.The use of stand-alone systems is discouraged, as they require double entry of data. Audit couldtake place on three levels: national, regional/local and practice level. The following arerecommended areas for audit.

National level

n stage shift in presentation of upper GI cancer

n use of a national referral form

Regional or local level

n the % of patients undergoing H. pylori test and treat before referral

n the % of patients referred for GI endoscopy who are less than 55 years of age without alarmfeatures

n the % of patients undergoing upper GI endoscopy who are less than 55 years of age withalarm features

Practice level

n prescribing of acid suppression therapy for functional dyspepsia

n success rate of primary H. pylori eradication

n the number of patients managed with a diagnostic code of functional dyspepsia.

6 IMPLEMENTATION AND AUDIT

8/3/2019 Sign 68 Full


DYSPEPSIA

n The efficacy and safety of the �test and treat� policy versus early upper GI endoscopy in themanagement of patients over 55 years of age presenting with recent onset uncomplicateddyspepsia.

n The management of functional dyspepsia with reference to lifestyle management, patienteducation, psychosocial interventions and pharmacological intervention.

n Definition of the age related risk of having upper GI cancer associated with a presentation of dyspepsia along with one of the commonly quoted alarm features

n A health economic study exploring whether short term increases in costs and work loadrelated to tests of H. pylori status and drugs involved in H. pylori eradication are related toany possible medium to long term savings from reductions in endoscopic investigations and

drugs to manage the symptoms of dyspepsia.n A study to explore whether wider use of antibacterial therapy and eradication of H. pylori are

associated with adverse effects.

6.4 RESOURCE IMPLICATIONS

The economic consequences of implementing this guideline are likely to include the following:

n an increase in the need for tests of H. pylori status

n an increase in the cost of drugs involved in H. pylori eradication regimesn a reduction in the need for endoscopic investigation of the GI tract, especially in younger

patients

n a reduction in the use of drugs to manage the symptoms of dyspepsia.

The economic consequences are difficult to quantify precisely at the local level. Impact willdepend on the following factors:

n the age of the population

n the prevalence and incidence of GI problemsn the existing management practice

n the availability of different investigations.

The following points form the suggested background to local budget impact calculations:

n There are short-term work implications for GPs in taking breath test samples, starting treatmentand reviewing progress but these should be offset by medium- to long-term savings as casesare resolved more quickly.

n Giving a CUBT sample is a straightforward procedure that can be done either at a brief hospital visit or by sending in a sample to the hospital for analysis. Analysis of the CUBTrequires specialist equipment and staff however and the capacity of local hospitals to manageCUBT samples should be kept under review.

8/3/2019 Sign 68 Full


7 Patient information

7.1 EXAMPLE PATIENT INFORMATION LEAFLET

The following points may be incorporated into local information materials for patients withdyspepsia.

What is Dyspepsia?

Dyspepsia is a general term used to describe discomfort or pain in the upper abdomen. It can be

called indigestion. Usually it disappears quite quickly but sometimes it is more persistent.What can you do about it?

You can go to your chemist who will advise on something to take to relieve the pain. If itcontinues to trouble you, you should go to see your family doctor.

What can the doctor do?

Dyspepsia can sometimes be caused by any one of several diseases so your doctor will try to findout if you have one of these.

In recent years a bacterium (called Helicobacter pylori) has been shown to contribute to dyspepsiain some patients and your doctor may decide to check whether it is present. This can be done bytaking a blood or stool sample or, with a breath-test (a simple procedure that involves blowinginto small test tubes). While waiting for results, your doctor may prescribe a drug to relieve thepain. If the bacterium is found your doctor may prescribe antibiotics to get rid of it.

If you have other symptoms along with the stomach pain your doctor may consider it is best foryou to see a specialist in hospital. At the hospital it may be decided to have a look inside usingan endoscope, a camera that is guided through the mouth to the stomach. Depending on what

the specialist sees, further treatment may be suggested. If there is no bacterium present and/ornothing untoward can be seen in the stomach this is good news.

In 70% of all patients with dyspepsia no disease can be found. This means it is not a seriouscomplaint but it can still be painful.

Although no medication has proved to be very effective it may be that your doctor will suggestand prescribe one which may help. He or she will also discuss your diet and lifestyle with youand may offer the following suggestions to improve things.

n giving up smokingn reducing the amount of alcohol and coffee or tea you drink

n avoiding foods which trigger your indigestion

n eating a balanced, healthy diet

n reducing stress in your life.

7 PATIENT INFORMATION

8/3/2019 Sign 68 Full


DYSPEPSIA

8 Development of the guideline

8.1 INTRODUCTION

SIGN is a collaborative network of clinicians, other health care professionals and patientorganisations funded by the Scottish Executive Health Department. SIGN guidelines are developedby multidisciplinary groups using a standard methodology based on a systematic review of theevidence. Further details about SIGN and the guideline development methodology are containedin �SIGN 50: A guideline developer�s handbook�, available at www.sign.ac.uk

8.2 THE GUIDELINE DEVELOPMENT GROUP

Ms Angela Timoney Consultant in Pharmaceutical Public Health,(Chairman) Kings Cross Hospital, DundeeMr Colin MacKay Consultant Surgeon, Victoria Infirmary, Glasgow (Secretary)Dr Robin Balfour General Practitioner, Murrayfield Medical Practice, EdinburghMrs Janice Bancroft Staff Nurse, Thoracic Unit,Hairmyres Hospital, East Kilbride

Mr Graham Bell Patient Representative, Penicuik Ms Anne Crozier GI Specialist Nurse, Ninewells Hospital, DundeeDr Michael Gray General Practitioner, Ancrum Medical Centre, DundeeDr Bob Heading Consultant Physician, Centre for Liver and Digestive Disorders,

Royal Infirmary, EdinburghMr Robin Harbour Quality and Information Director, SIGNDr Stuart Hislop Consultant Gastroenterologist,

Royal Alexandra Hospital, Paisley Mrs Phoebe Isard Patient Representative, EdinburghMs Moira Kinnear Principal Pharmacist, Western General Hospital, EdinburghProfessor Kenneth McColl Director of Gastroenterology, Western Infirmary,Glasgow Dr John Murchison Consultant Radiologist, Royal Infirmary, EdinburghMr William R Murray Consultant Surgeon, Lister Department of Surgery,

Glasgow Royal Infirmary Dr Stephanie Norris Medical Director, North Cumbria Acute Hospitals, CarlisleMrs Fiona Phillips Senior Dietitian, Western General Hospital, EdinburghDr Rita Rigg General Practitioner, Hermitage Medical Practices, Edinburgh

Dr Jack Taylor General Practitioner, Aboyne Medical Practice, AberdeenshireMs Joanne Topalian Programme Manager, SIGNDr Craig Williams Consultant Medical Microbiologist,

Yorkhill NHS Trust, Glasgow

The membership of the guideline development group was confirmed following consultationwith the member organisations of SIGN. Declarations of interests were made by all members of

8 DEVELOPMENT OF THE GUIDELINE

8/3/2019 Sign 68 Full


8.3 SYSTEMATIC LITERATURE REVIEW

The evidence base for this guideline was synthesised in accordance with SIGN methodology. Asystematic review of the literature was carried out using an explicit search strategy devised by theSIGN Information Officer in collaboration with members of the guideline development group.

Searches were restricted to systematic reviews, meta-analyses, RCTs, and longitudinal studies.Internet searches were carried out on the Web sites of the Canadian Practice Guidelines Infobase,the New Zealand Guidelines Programme, the UK Health Technology Assessment Programme,the US National Guidelines Clearinghouse, and the US Agency for Healthcare Research andQuality. Searches were also carried out using Google and OMNI search engines, and all suitable

links followed up. Database searches were carried out on Cochrane Library, Embase 1990 to2000, and Medline 1990 to 2000. Embase and Medline searches were later extended back to1980 in relation to specific questions where more recent evidence was lacking. All searches werelater updated to 2001.

An independent information specialist reviewed the search strategies. The Medline version of themain search strategies is available on the SIGN Web site, in the section covering supportingmaterial for published guidelines. The main searches were supplemented by material identifiedby individual members of the development group. All selected papers were evaluated usingstandard methodological checklists before conclusions were considered as evidence.

8.4 CONSULTATION AND PEER REVIEW

8.4.1 NATIONAL OPEN MEETING

The national open meeting is the main consultative phase of SIGN guideline development, atwhich the guideline development group presents their draft recommendations for the first time.The national open meeting for this guideline was held in October 2001 and was attended by all

of the key specialties relevant to the guideline. The draft guideline was also available on theSIGN web site for a limited period at this stage to allow those unable to attend the meeting tocontribute to the development of the guideline.

8.4.2 SPECIALIST REVIEW

The guideline was also reviewed in draft form by a panel of independent expert referees, whowere asked to comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting the recommendations in the guideline. SIGN is very grateful to allof these experts for their contribution to this guideline.

Dr Pablo Alonso Iberoamerican Cochrane Centre, BarcelonaProfessor John Atherton University Hospital, NottinghamMr Charles Auld Consultant Surgeon, Dumfries & Galloway NHS TrustDr James Beattie Director of Guidelines, Royal College of General PractitionersDr Alan Begg General Practitioner, MontroseM J i Bi ll S i h E i H l h Pl i d Q li Di i i

8 DEVELOPMENT OF THE GUIDELINE

DYSPEPSIA

8/3/2019 Sign 68 Full


DYSPEPSIA

Mr Ron MacLeod Associate Director of Nursing,Tayside Primary Care NHS Trust

Dr George Masterton Consultant Psychiatrist, Royal Infirmary of EdinburghDr Alan Merry General Practitioner, ArdrossanProfessor Paul Moayyedi Professor of Gastroenterology Health Services Research,

City Hospital NHS Trust, BirminghamMr Kenneth Park Consultant Surgeon, Aberdeen Royal Infirmary Dr Andrew Power Head of Medicines Management Team,

Gartnavel Royal Hospital, Glasgow Ms Patricia Purton Director, Royal College of Midwives, Edinburgh

Dr Alan Shepherd Consultant Physician and Gastroenterologist,Perth Royal Infirmary Dr Hamish Simpson General Practitioner,West Kilbride, AyrshireDr Philip Shorvon Consultant Radiologist, Central Middlesex Hospital, LondonMr Alistair Thompson Consultant Surgeon, Ninewells Hospital, DundeeDr Sander Veldhuyzen Consultant Gastroenterologist, Dalhousie University, Halifax, Canada

Van ZantenDr Marten Walker General Practitioner, Stornoway Dr Hugh Whyte Senior Medical Officer, Primary Care Directorate,

Scottish ExecutiveMs Kerry Yuill Dietitian, Royal Infirmary, Edinburgh

8.4.3 EDITORIAL GROUP

As a final quality control check, the guideline is reviewed by an Editorial Group comprising therelevant specialty representatives on SIGN Council to ensure that the peer reviewers� commentshave been addressed adequately and that any risk of bias in the guideline development process asa whole has been minimised. The Editorial Group for this guideline was as follows:

Dr David Alexander British Medical Association Scottish General Practice CommitteeDr Douglas Harper Royal College of Surgeons of EdinburghProfessor Gordon Lowe Chairman, SIGN; Co-EditorDr Lesley MacDonald Faculty of Public Health MedicineMs Fiona McMillan Lead Pharmacist, North Glasgow NHS TrustDr Safia Qureshi Programme Director, SIGNDr Bill Reith Chairman, Royal College of General Practitioners, EdinburghDr Sara Twaddle Director, SIGN; Co-Editor

ANNEX 1

8/3/2019 Sign 68 Full


Annex 1

SIGN guideline number 7 produced in 1997 and the update to this published in 1999 eachcontained a table detailing the evidence for H. pylori eradication in duodenal ulcer, gastric ulcerand gastric lymphoma.1,2 This evidence has been updated by the dyspepsia guideline developmentgroup (see below).

1.1 WHICH PATIENTS WITH H. PYLORI SHOULD RECEIVE ERADICATION THERAPY?

1.2 H. PYLORI ERADICATION OPTIONS

The evidence base for H. pylori eradication options has also improved since the previous SIGNguidelines were published. An update of the numbers of medicines to use, the duration of treatment and the influence of known antimicrobial resistance are given below.

Dual therapies eradicate H. pylori from fewer people than triple therapies114

n

Triple therapies including PPIs and two antibiotics give consistently high eradication ratesn Metronidazole or clarithyromycin resistance established by laboratory testing is associated

with reduced eradication of H. pylori by regimens including these antibiotics

n Two weeks of triple therapy versus a one week regimen does not increase the eradication rate.

Eradicate?Grade of

RecommendationLevel of Evidence

Yes A 1+Duodenal ulcer111

Yes A 1+Gastric ulcer111

Yes B 2+Low grade gastric MALTLymphoma112,113

ANNEX 1

DYSPEPSIA

8/3/2019 Sign 68 Full


DYSPEPSIA

Annex 2

Selection of Diagnostic Tests

When considering how useful diagnostic tests are in differentiating people with disease fromhealthy people reference is frequently made to the sensitivity, specificity, positive predictivevalue, and negative predictive value of a test. These terms are defined as follows:

From this the following can be calculated:

Positive Predictive value (PPV) is a function of the True and False positive values. If there wereno false positives, the PPV would be TP/TP or 100%. In the real world this is rarely the case aslaboratory results usually fall on a continuous scale and a cut off has to be selected to separatepositive from negative results. As such there is some degree of overlap between results fromnormal and affected patients.

It is theoretically possible that everyone in the population has a disease. In this case everypositive result would be a true positive and the PPV would be 100%. Conversely, if no one inthe population had the disease, every positive result would be a false positive. There could be notrue positives, and the PPV would be 0%. This makes it clear that the prevalence of a disease inthe population has an important influence on the positive predictive value of a diagnostic test.With decreasing disease prevalence, the less likely it becomes that a person with a positive testresult has the disease, and the more likely it becomes that the positive result is a false positive.The diagnostic accuracy of a test therefore depends upon the prevalence of the disease in thepopulation. The table below outlines how the positive and negative predictive values of allcommonly used diagnostic tests vary by prevalence, using the published sensitivity and specificities

quoted in the text (see section 4) for each test.Serology tests

Primary Care

Laboratory based

serology tests

Prevalence of

H. pylori

PPV

CUBTFaecal

antigen tests

NPV PPV NPV PPV NPV PPV NPV

0.1% 15% 99% 0.5% 99% 2% 99% 1% 00%

5% 43% 99% 21% 99% 55% 99% 33% 99%

Test Positive Test Negative

True Positive (TP) False Negative (FN)Patient with diseaseFalse Positive (FP)Normal patient True Negative (TN)

CalculationValue

TP/(TP+FN)Sensitivity

TN/(TN+FP)Specificity

TP/(TP+FP)Positive predictive value (PPV)

TN/(TN+FN)Negative predictive value (NPV)

REFERENCES

8/3/2019 Sign 68 Full


9 References

1 Scottish Intercollegiate Guidelines Network (SIGN). Helicobacter pylori:eradication therapy in dyspeptic disease. Edinburgh: SIGN; 1997. (SIGNpublication no.7).

2 Scottish Intercollegiate Guidelines Network (SIGN). Helicobacter pylori:eradication therapy in dyspeptic disease. Update. Edinburgh: SIGN; 1999.(SIGN publication no.7).

3 Jones RH, Lydeard SE, Hobbs FD, Kenkre JE, Williams EI, Jones SJ, et al. Dyspepsiain England and Scotland. Gut 1990;31:401-5.

4 Penston JG, Pounder RE. A survey of dyspepsia in Great Britain. AlimentPharmacol Ther 1996;10:83-9.

5 Stanghellini V. Three-month prevalence rates of gastrointestinal symptoms andthe influence of demographic factors: results from the Domestic/InternationalGastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol Suppl1999;231:20-8.

6 NHS Scotland. Information and Statistics Division. Prescription cost analysisfor Scotland. Edinburgh: The Division; 2002. [cited 20 Nov 2002]. Availablefrom url: http://www.show.scot.nhs.uk/isd/primary_care/pservices/ pcare_spa_data.htm

7 Haycox A, Einarson T, Eggleston A. The health economic impact of upper gastrointestinal symptoms in the general population: results from the Domestic/ International Gastroenterology Surveillance Study (DIGEST). Scand JGastroenterol Suppl 1999;231:38-47.

8 Talley NJ, Weaver AL, Zinsmeister AR. Impact of functional dyspepsia on qualityof life. Dig Dis Sci 1995;40:584-9.9 Enck P, Dubois D, Marquis P. Quality of life in patients with upper

gastrointestinal symptoms: results from the Domestic/InternationalGastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol Suppl1999;231:48-54.

10 Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN.Functional gastroduodenal disorders. Gut 1999;45:II37-42.

11 The Proprietary Association of Great Britain. Annual report 2001. UK Marketsize statistics 1999/2000. London: The Association; 2001. [cited 26 Aug 2002].Available from url: http://www.pagb.co.uk/src/About_PAGB/ Annual_Report_01/section05.htm

12 Krishnan HS, Schaefer M. Evaluation of the impact of pharmacist�s advice

giving on the outcomes of self-medication in patients suffering form dyspepsia.Pharm World Sci 2000;22:102-8.

13 Krska J, John DN, Hansford D, Kennedy EJ. Drug utilization evaluation of nonprescription H2-receptor antagonists and alginate-containing preparationsfor dyspepsia. Br J Clin Pharmacol 2000;49:363-8.

14 Hansen JM, Bytzer P, Schaffalitzky De Muckadell OB. Management of dyspepticpatients in primary care. Value of the unaided clinical diagnosis and of dyspepsiasubgrouping. Scand J Gastroenterol 1998;33:799-805.

15 Bytzer P, Moller Hansen JM, Schaffalitzky De Muckadell OB, Malchow-Moller A. Predicting endoscopic diagnosis in the dyspeptic patient. Scand. JGastroenterol 1997;32:118-25.

16 Mann J, Holdstock G, Harman M, Machin D, Loehry CA. Scoring System to

improve cost effectiveness of open access endoscopy. BMJ 1983;287:937-40.17 Holdstock G, Harman M, Machin D, Patel C, Lloyd RS. Prospective testing of

a scoring system designed to improve case selection for upper gastrointestinalinvestigation. Gastroenterology 1986;90:1164-9.

18 American Gastroenterological Association medical position statement:evaluation of dyspepsia. Gastroenterology 1998;114:579-81.

19 Department of Health. Referral Guidelines for suspected cancer. London:The Department; 2000 [cited 26 Aug 2002] Available from url: http://

27 Gilbert FJ, Park KGM, Thompson AM, editors. Scottish Audit of Gastric andOesophageal Cancer. Report 1997-2000. A prospective audit. Edinburgh:Scottish Executive Health Department; 2002. [cited 25 Nov 2002]. Availablefrom url: http://www.show.scot.nhs.uk/crag/committees/CEPS/reports/ 0_prelims.pdf

28 Talley NJ, Axon A, Bytzer P, Holtmann G, Lam SK, Van Zanten S. Managementof uninvestigated and functional dyspepsia: a Working Party report for theWorld Congresses of Gastroenterology 1998. Aliment Pharmacol Ther 1999;13:1135-48.

29 Ofman JJ, Rabeneck L. The effectiveness of endoscopy in the management of dyspepsia: a qualitative systematic review. Am J Med 1999;106:335-46.

30 Shaw PC, van Romunde LK, Griffioen G, Janssens AR, Kreuning J, Lamers CB.Detection of gastric erosions: comparison of biphasic radiography withfiberoptic endoscopy. Radiology 1991;178:63-6.

31 Stevenson GW, Norman G, Frost R, Somers S. Barium meal or endoscopy? A

prospective randomised study of patient preference and physician decisionmaking. Clin Radiol 1991;44:317-21.

32 Simpkins KC. What use is barium? Clin Radiol 1988;39:469-73.33 Royal College of Radiologists. Making the best use of a department of clinical

radiology. Guidelines for doctors. 4th ed. London: The College; 1998.34 The ionising radiation (medical exposure) regulations 2000. London: The

Stationery Office; 2000. (Statutory instruments no. 1059). [cited 27 Aug 2002].Available from url: http://www.hmso.gov.uk/si/si2000/20001059.htm

35 Stevens R, Baxter G. Benefit of Helicobacter pylori eradication in the treatmentof ulcer-like dyspepsia in primary care [abstract]. Digestive disease week. AGA(American Gastroenterological Association). Atlanta, 19-23 May 2001.Congress Review en Gastroenterología y Hepatología; 2001.[cited 20 Nov 2002]. Available from url: http://www.congressreview.com/ gastro/aga-01/42.htm

36 Hentschel E, Brandstatter G, Dragosics B, Hirschl AM, Nemec H, Schutze K,et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradicationof Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med1993;328:308-12.

37 Axon AT, O�Morain CA, Bardhan KD, Crowe JP, Beattie AD, Thompson RP,et al. Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection. BMJ1997;314:565-8.

38 Delaney B, Moayyedi P, Deeks J, Innes M, Soo S, Barton P, et al. Themanagement of dyspepsia: a systematic review. Health Technol Assess 2000;4.[cited 4 Sep 2002]. Available from url: http://www.hta.nhsweb.nhs.uk/

fullmono/mon439.pdf 39 Delaney BC, Innes MA, Deeks J, Wilson S, Cooner MK, Moayyedi P, Oakes

R, Hobbs FDR, Forman D. Initial management strategies for dyspepsia(Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford: UpdateSoftware.

40 Delaney BC, Wilson S, Roalfe A, Roberts L, Redman V, Wearn A, et al.Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care. BMJ 2001;322:898-901.

41 Heaney A, Collins JS , Watson RG , McFarland RJ, Bamford KB, Tham TC. Aprospective randomised trial of a �test and treat� policy versus endoscopybased management in young helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic. Gut 1999;45:186-190.

42 Patel P, Khulusi S, Mendall MA, Lloyd R, Jazrawi R, Maxwell JD, et al. Prospectivescreening of dyspeptic patients by Helicobacter pylori serology. Lancet1995;346:1315-8.

43 Lassen AT, Pedersen FM, Bytzer P, Schaffalitzky de Muckadell OB. Helicobacter pylori test-and-eradicate versus prompt endoscopy for management of dyspeptic patients: a randomised trial. Lancet 2000;356:455-60.

44 Jones R, Tait C, Sladen G, Weston-Baker J. A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice. Int J ClinPract 1999;53:413-6.

C S

DYSPEPSIA

8/3/2019 Sign 68 Full


52 Scottish Executive Department of Health. Scottish referral guidelines for suspected cancer. Edinburgh: The Department; 2002. [cited 27 Aug 2002].Available from url: http://www.show.scot.nhs.uk/sehd/cancerinscotland/

DocumentsScottish%20Referral%20Guidelines%20for%20Suspected%20Cancer.pdf 53 Chiba N, Van Zanten SJ, Sinclair P, Ferguson RA, Escobedo S, Grace E. Treating

Helicobacter pylori infection in primary care patients with uninvestigateddyspepsia: the Canadian adult dyspepsia empiric treatment-Helicobacter pyloripositive (CADET-Hp) randomised controlled trial. BMJ 2002;324:1012-6.

54 Laheij RJ, Severens JL, Van de Lisdonk EH, Verbeek AL, Jansen JB. Randomizedcontrolled trial of omeprazole or endoscopy in patients with persistentdyspepsia: a cost-effectiveness analysis. Aliment Pharmacol Ther 1998;12:1249-56.

55 McNulty CA, Wyatt JI. ACP Best practice no 154. February 1999. Helicobacter pylori. J Clin Pathol 1999;52:338-44.

56 Klein PD, Malaty HM, Martin RF, Graham KS, Genta RM, Graham DY.

Noninvasive detection of Helicobacter pylori infection in clinical practice: the13C urea breath test. Am J Gastroenterol 1996;9:690-4.

57 El-Nujumi A, Hilditch TE, Williams C, McColl KE. Current or recent protonpump inhibitor therapy markedly impairs the accuracy of the [14C]urea breathtest. Eur J Gastroenterol Hepatol 1998;10:759-64.

58 Loy CT, Irwig LM, Katelaris PH, Talley NJ. Do commercial serological kits for Helicobacter pylori infection differ in accuracy? A meta-analysis. Am JGastroenterol 1996;91:1138-44.

59 Stevens M, Livsey S, Swann RA, Rathbone BJ. Evaluation of sixteen EIAs for thedetection of antibodies to Helicobacter pylori. London: Medical DevicesAgency; 1997.

60 Roberts AP, Childs SM, Rubin G, de Wit NJ. Tests for Helicobacter pyloriinfection: a critical appraisal from primary care. Fam Pract 2000;17:S12-20.

61 Laheij RJ, Straatman H, Jansen JB, Verbeek AL. Evaluation of commerciallyavailable Helicobacter pylori serology kits: a review. J Clin Microbiol1998;36:2803-9.

62 Vaira D, Vakil N. Blood, urine, stool, breath, money, and Helicobacter pylori.Gut 2001;48:287-9.

63 Oksanen A, Veijola L, Sipponen P, Schauman KO, Rautelin H. Evaluation of Pyloriset Screen, a rapid whole-blood diagnostic test for Helicobacter pyloriinfection. J Clin Microbiol 1998;36:955-7.

64 Duggan AE, Hardy E, Hawkey CJ. Evaluation of a new Near Patient Test for thedetection of Helicobacter pylori. Eur J Gastroenterol Hepatol 1998;10:133-6.

65 Ishihara S, Kaji T, Kawamura A, Rumi MA, Sato H, Okuyama T, et al. Diagnostic

accuracy of a new non-invasive enzyme immunoassay for detectingHelicobacter pylori in stools after eradication therapy. Aliment PharmacolTher 2000;14:611-4.

66 Manes G, Balzano A, Iaquinto G, Ricci C, Piccirillo MM, Giardullo N, et al.Accuracy of the stool antigen test in the diagnosis of Helicobacter pyloriinfection before treatment and in patients on omeprazole therapy. AlimentPharmacol Ther 2001;15:73-9.

67 Weijnen CF, Hendriks HA, Hoes AW, Verweij WM, Verheij TJ, de Wit NJ.New immunoassay for the detection of Helicobacter pylori infection comparedwith urease test, 13C breath test and histology: validation in the primary caresetting. J Microbiol Methods 2001;46:235-40.

68 Vaira D, Malfertheiner P, Megraud F, Axon AT, Deltenre M, Gasbarrini G. etal. Noninvasive antigen-based assay for assessing Helicobacter pylorieradication: a European multicenter study. The European Helicobacter pyloriHpSA Study Group. Am J Gastroenterol 2000;95:925-9.

69 Gisbert JP, Blanco M, Benito LM, Pajares JM. Value of quantitative serology for confirmation of Helicobacter pylori eradication: an 18-month follow-up study.Clin Infect Dis 2000;30:976-80.

70 Lydeard S, Jones R. Factors affecting the decision to consult with dyspepsia:comparison of consulters and non-consulters. J R Coll Gen Pract 1989;39:495-8.

78 Stanghellini V. Relationship between upper gastrointestinal symptoms andlifestyle, psychosocial factors and comorbidity in the general population: resultsfrom the Domestic/International Gastroenterology Surveillance Study

(DIGEST). Scand J Gastroenterol Suppl 1999;231:29-37.79 Woodward M, Morrison CE, McColl KE. The prevalence of dyspepsia and

use of antisecretory medication in North Glasgow: role of Helicobacter pylorivs. lifestyle factors. Aliment Pharmacol Ther 1999;13:1505-9.

80 Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ 3rd. Smoking, alcohol andanalgesics in dyspepsia and among dyspepsia subgroups: lack of an associationin a community. Gut 1994;35:619-24.

81 Hamilton J, Guthrie E, Creed F, Thompson D, Tomenson B, Bennett R, et al.A randomized controlled trial of psychotherapy in patients with chronicfunctional dyspepsia. Gastroenterology 2000;119:661-9.

82 Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D. Psychologicalinterventions for non-ulcer dyspepsia. (Cochrane Review). In: The Cochrane

Library, Issue 3 2002. Oxford: Update Software.83 Blum AL, Talley NJ, O�Morain C, van Zanten SV, Labenz J, Stolte M, et al. Lack

of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxicillin Effect One Year after Treatment (OCAY) Study Group. N Engl J Med 1998;339:1875-81.

84 Talley NJ, Vakil N, Ballard ED 2nd, Fennerty MB. Absence of benefit of eradicating Helicobacter pylori in patients with nonulcer dyspepsia. N Engl JMed 1999;341:1106-11.

85 McColl K, Murray L, El-Omar E, Dickson A, El-Nujumi A, Wirz A, et al.Symptomatic benefit from eradicating Helicobacter pylori infection in patientswith nonulcer dyspepsia. N Engl J Med 1998;339:1869-74.

86 Talley NJ, Janssens J, Lauritsen K, Racz I, Bolling-Sternevald E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebocontrolled trial with 12 months� follow up. The Optimal Regimen CuresHelicobacter Induced Dyspepsia (ORCHID) Study Group. BMJ1999;318:833-7.

87 Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes M, et al. Systematicreview and economic evaluation of Helicobacter pylori eradication treatmentfor non-ulcer dyspepsia. BMJ 2000;321:659-64.

88 Laine L, Schoenfeld P, Fennerty MB. Therapy for Helicobacter pylori in patientswith nonulcer dyspepsia. A meta-analysis of randomized, controlled trials.Ann Intern Med 2001;134:361-9.

89 Danesh J, Lawrence M, Murphy M, Roberts S, Collins R. Systematic review of the epidemiological evidence on Helicobacter pylori infection and nonulcer or uninvestigated dyspepsia. Arch Intern Med 2000;160:1192-8.

90 Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes M, et al. Eradicationof Helicobacter pylori for non-ulcer dyspepsia (Cochrane Review). In: TheCochrane Library, Issue 3, 2001. Oxford: Update Software.

91 Talley NJ, Meineche-Schmidt V, Pare P, Duckworth M, Raisanen P, Pap A, etal. Efficacy of omeprazole in functional dyspepsia: double-blind, randomized,placebo-controlled trials (the Bond and Opera studies). Aliment PharmacolTher 1998;12:1055-65.

92 Halter F, Miazza B, Brignoli R. Cisapride or cimetidine in the treatment of functional dyspepsia. Results of a double-blind, randomized, Swiss multicentrestudy. Scand J Gastroenterol 1994;29:618-23.

93 Carvalhinhos C, Fidalgo P, Freire A, Matos L. Cisapride compared withranitidine in the treatment of functional dyspepsia. Eur J Gastroenterol Hepatol1995;7:411-7.

94 Farup P, Wetterhus M, Osnes M, Ulshagen K. Ranitidine effectively relievessymptoms in a subset of patients with functional dyspepsia. Scand JGastroenterol 1997;8:755-9.

95 Meineche-Schmidt V, Talley NJ, Pap A, Kordecki H et al. Impact of functionaldyspepsia on quality of life and health care consumption after cessation of antisecretory treatment. Scand J Gastroenterol 1999;6:566-74.

96 Shukla VK, Otten N, Dubé C, Moher D. Use of cisapride in patients with non-ulcer dyspepsia: a meta-analysis of randomized trials. Ottawa: Canadian

REFERENCES

8/3/2019 Sign 68 Full


103 Hausken T, Stene-Larsen G, Lange O, Aronsen O, Nerdrum T, Hegbom F, etal. Misoprostol treatment exacerbates abdominal discomfort in patients withnon-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-

controlled, multicentre study. Scand J Gastroenterol 1990;25:1028-33.104 Jackson JL, O�Malley PG, Tomkins G, Balden E, Santoro J, Kroenke K. Treatment

of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med 2000;108:65-72.

105 Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients withfunctional dyspepsia. Am J Gastroenterol 1998;93:160-5.

106 Tanum L, Malt UF. A new pharmacologic treatment of functional gastrointestinaldisorder. A double-blind placebo-controlled study with mianserin. Scand JGastroenterol 1996;31:318-25.

107 Lindell GH, Celebioglu F, Graffner HO. Non-ulcer dyspepsia in the long-termperspective. Eur J Gastroenterol Hepatol. 1995;7:829-33.

108 Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ 3rd. Dyspepsia and dyspepsiasubgroups: a population-based study. Gastroenterology 1992;102:1259-68.

109 Talley NJ, Boyce P, Jones M. Identification of distinct upper and lower gastrointestinal symptom groupings in an urban population. Gut1998;42:690-5.

110 Agreus L, Svardsudd K, Nyren O, Tibblin G. Irritable bowel syndrome anddyspepsia in the general population: overlap and lack of stability over time.Gastroenterology 1995;109:671-80.

111 Leodolter A, Kulig M, Brasch H, Meyer-Sabellek W, Willich SN, Malfertheiner P. A meta-analysis comparing eradication, healing and relapse rates in patientswith Helicobacter pylori-associated gastric or duodenal ulcer. AlimentPharmacol Ther 2001;15:1949-58.

112 Sackmann M, Morgner A, Rudolph B, Neubauer A, Thiede C, Schulz H, et al.Regression of gastric MALT lymphoma after eradication of Helicobacter pyloriis predicted by endosonographic staging. MALT Lymphoma Study Group.Gastroenterology 1997;113:1087-90.

113 Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, et al.Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue.An uncontrolled trial. Ann Intern Med 1999;131:88-95.

114 Delaney B, Moayyedi P, Forman D. Helicobacter pylori infection. In: Clinicalevidence. 8th ed. London: BMJ Publishing Group; 2002. p. 453-68.

8/3/2019 Sign 68 Full


Sign 68 Full

Documents

Transcript of Sign 68 Full