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| Journal of the New Zealand Medical Association,
20-June-2003, Vol 116 No 1176
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Nurse-led dyspepsia clinic using the urea breath test for
Helicobacter pylori
Alan Fraser, Susan Williamson, Mark Lane and Brian
Hollis
The assessment of dyspepsia by symptoms alone is difficult.
Gastroscopy has been the main investigative tool to guide management. However,
there are limited resources for endoscopy for the investigation of dyspepsia.
There is, therefore, significant interest in non-invasive diagnostic tests and
empiric therapies for the initial management of dyspepsia. Symptoms can be
difficult to interpret and, in particular, have low discriminative value for
peptic ulcer disease.1–4 Testing for
Helicobacter pylori can be useful to
identify patients at higher risk of peptic ulcer disease. A previous
general-practice-based study using the urea breath test as the initial
assessment tool suggested that symptom relief (by
H. pylori eradication) and adequate
reassurance (if the treat was negative) was possible without gastroscopy in a
significant proportion of patients.5
The demand for gastroscopy is in excess of the resources
available at many New Zealand hospitals. We therefore decided to trial a
test-and-treat approach using a hospital-based, nurse-led clinic. Nursing
involvement in the consultation process had been successful in other areas of
the activities of the Gastroenterology Department at Auckland Hospital,
particularly in the management of patients with hepatitis C. Therefore, this
approach was chosen as the appropriate strategy for the dyspepsia clinic. This
study seeks to evaluate if this process was successful for the majority of
patients.
MethodsSelected referrals to the
Gastroenterology Department of patients with dyspepsia (usually including a
request for gastroscopy) were assessed in a dyspepsia clinic rather than
proceeding directly to gastroscopy. The selection was performed by consultant
staff and based only on data in the referral letter. There was some bias towards
selecting patients with ‘ulcer-type dyspepsia’ and/or any history of
peptic ulceration in the past. There was also some bias towards selection of
patients born outside New Zealand (including recent immigrants) in whom the
chance of finding H. pylori infection
was known to be greater.4,6 The intention of
the clinic was to select patients with uninvestigated dyspepsia who had not had
previous eradication treatment for H.
pylori.
Initial evaluation consisted of a consultation by the project nurse and a urea breath test (UBT). Data from the clinic were prospectively collected on ethnicity, place of birth, recent use of proton pump inhibitors, recent antibiotic use and previous attempts at eradication treatment. Symptom evaluation included selecting the dominant symptom – epigastric pain, reflux, both epigastric and reflux, bloating, abdominal pain – and a grading of severity – mild, moderate, severe. Interpreters were used whenever required. The breath test was performed using a method previously described and validated in our department.7 The appropriate cut-off point was determined from a long-term follow-up study. A negative breath test was defined as a delta (δ) 13CO2 value of 0–2, an indeterminate test had a δ 13CO2 value of 2–4 and a definite positive breath test had a δ 13CO2 value of >4.7 Patients were asked to stop using proton pump inhibitors prior to the urea breath test. Patients with a positive UBT were given eradication treatment for H. pylori. The main treatment used was ranitidine bismuth citrate (Pylorid, supplied by Glaxo), metronidazole and clarithyromycin. The results of an audit of this treatment have been previously reported.8 Patients were reviewed two months later for symptom assessment and a follow-up UBT. Patients with continuing symptoms were referred for gastroscopy at the discretion of the nurse. Patients were contacted by letter and telephone with the results and contacted again if they failed to attend appointments. The endoscopy database was searched at the end of the follow-up period to find any patients referred directly back to the Gastroenterology Department for gastroscopy without coming via the project nurse. Some patients were randomly selected to have a blood test for H. pylori serology collected at the time of initial assessment. This was stored at -80oC then analysed as a batch in the Microbiology Laboratory at Middlemore Hospital. The method used the Cobas Core Anti-H. pylori EIA quantitative test for IgG antibodies (Roche). A cut-off point of 6 U/ml was used as per manufacturer recommendations. Values within the range of 5.4–6.6 U/ml were considered indeterminate and the test was repeated. If the samples remained in the indeterminate range they were assigned to a positive or negative value using the 6 U/ml cut-off point. ResultsData were collected prospectively
for 226 patients who were seen for initial evaluation during the period November
1997 to August 2001. Fifty three patients had been given previous eradication
treatment and were excluded. Subsequent analysis was performed on the 173
patients who had not been given treatment (this was the group of uninvestigated
and untreated dyspepsia patients that was intended for the dyspepsia clinic).
The mean age was 38 years; there were 91 males and 82 females.
Seventy three patients (42%) had a positive UBT. Two
patients had an intermediate result. Of these, one patient proceeded to
gastroscopy – this was normal and the biopsy tests negative for
H. pylori. The other patient had
eradication treatment and the follow-up UBT was negative. A positive UBT was
significantly associated with place of birth. Of patients born in New Zealand or
Western Europe 16% had a positive UBT compared with 60% positivity for patients
born in other parts of the world combined (p = 0.001, Table 1). Of those with
epigastric pain as the dominant symptom 54% had a positive UBT compared with 29%
if the dominant symptom was reflux or bloating (p = 0.005). UBT positivity was
not related to age or gender.
Table 1. Urea breath test results according to place of
birth
*two patients had intermediate urea breath test results
and were excluded
Forty nine patients who had been given eradication treatment
returned for symptom review and a follow-up UBT. Successful eradication was
confirmed in 43 patients (88%). Data on symptom response were available for 40
patients. For patients with successful eradication, 40% had an excellent
response with no or minimal symptoms, 38% had improved, and 22% had not improved
(same symptoms or worse, Table 2). Patients with a negative UBT were usually
referred back to the general practitioner. Many patients had a treatment trial
with a proton pump inhibitor following the negative UBT result.
Table 2. Symptom response assessed at two months after
eradication treatment
*data on symptom response not available for three
patients
Forty two patients were referred for gastroscopy (24%),
either directly by the project nurse or later by referral from the general
practitioner over a mean period of follow up of 3.3 years (range 1–4.8
years). Thirty of the 100 patients who were breath-test negative (including two
patients with intermediate results) had a gastroscopy – 16 were normal, 13
showed reflux oesophagitis, and one had duodenitis.
H. pylori tests (CLO and histology)
were negative in all patients. Twelve of the 73 patients (16%) with a positive
breath test were referred for endoscopy after eradication treatment had been
given. Nine of these patients had
successful eradication – eight were normal, one had pylori stenosis. Three
had persisting H. pylori infection
– two had a normal gastroscopy and one had a gastric ulcer (Table
3).
Table 3. Summary of endoscopy findings for the 42
patients (24%) referred for gastroscopy during the follow-up period (mean 3
years)
*number of patients initially
H. pylori positive who had successful
eradication treatment; †two patients with
intermediate results included with negative breath test patients
H.
pylori serology One hundred and
thirteen patients also had H. pylori
serology performed on a blood sample taken at the initial visit (random
selection for serology). The comparison with the UBT results is shown in Table
4. There were three false negatives (quantitative IgG levels of 5.3, 4.1 and 3.0
U/ml) giving a negative predictive value (NPV) of 94% (51/54). There were 7
false positives (quantitative IgG levels of 6.2, 6.3, 7.4, 8.9, 9.1, 12.0 and
83.9 U/ml). (Two patients had reasons for falsely negative UBT – one
patient was on Denol and one was taking Augmentin. These patients were excluded
from analysis.) The adjusted positive predictive value (PPV) of
H. pylori serology was 88% (52/59). The
cut-off point of 6 U/ml was found to be appropriate. The accuracy of the
H. pylori serology test could not have
been improved with any alternative cut-off point.
Table 4. Comparsion of
H. pylori serology with the urea breath
test (UBT)
PPV = postive predictive value; NPV = negative
predictive value
*two patients excluded – one was on Augmentin and the other Denol at the time of the UBT DiscussionThe study confirms good symptom
relief for H. pylori-positive patients
treated with eradication treatment. The potential benefit from
H. pylori eradication in patients with
uninvestigated dyspepsia largely depends on the proportion with peptic ulcer
disease. The symptomatic benefit gained from
H. pylori eradication where there is
not an ulcer is debatable but appears to be modest at
best.10,11 Many patients in this study had a
suggestive history of ulcer disease or some evidence of ulcer disease in the
past (the true proportion with ulcer disease cannot be determined with a
test-and-treat policy). The chance of finding a peptic ulcer disease in a
patient with dyspepsia and a positive UBT, if a prompt gastroscopy is performed
before any treatment is given, has been found to be surprisingly high in some
studies. A study from South Auckland showed that 47% of patients with
uninvestigated dyspepsia who had a positive breath test had evidence of current
or previous peptic ulcer disease.4 Similar
results have been reported in studies from Glasgow, London and
Denmark.12–14 The
H. pylori test-and-treat strategy is
likely to be more effective if patients with predominant reflux symptoms are
excluded. The relatively high proportion of patients with a positive test for
H. pylori reflects the ethnic
background of patients seen in Auckland. The result was similar to that observed
in a UBT study performed in general practices in South
Auckland.4 The data are likely to have been
very different if the study had been conducted in Christchurch or Dunedin where
the background prevalence of H. pylori
is much lower.9,15
Patients with a negative UBT were reassured and treated as
required based on symptoms. In this study, 24% of patients were referred for
gastroscopy after a mean follow up of 3.3 years. There is a possibility that
some patients obtained gastroscopy outside of Auckland Hospital but the numbers
are likely to be small. The reasons for referral for gastroscopy were individual
and varied. They related more to patient anxiety and the perceived inadequate
reassurance without a gastroscopy rather than the nature of the symptoms. Most
patients who eventually came to gastroscopy were
H. pylori negative and had
‘reflux-type’ symptoms. In the previous general-practice-based
breath test study H. pylori-negative
patients were followed up after a mean of 17 months and 20% had required a
gastroscopy at the time of follow up.4 It is
likely that the demand for gastroscopy was reduced by the test-and-treat
strategy but longer follow up will be required to determine whether or not this
effect is simply due to delayed referral. Other test-and-treat studies that have
follow up adequate to show the proportion of patients referred for gastroscopy
at a later date are summarized in Table 5 along with this
study.16–20 The location of breath test
facilities – hospital or primary care – does not appear to be
critical. Beshardas et al, in a similar hospital-based breath test clinic,
followed 190 patients who had been initially referred for gastroscopy and only
10.5% were referred back for gastroscopy after a two-year follow
up.18 The proportion of patients satisfied with
non-invasive testing depends on the level of follow up, the degree and type of
reassurance given, and the availability of endoscopy. In a randomized study by
Lassen et al, 500 primary care patients from 65 practices were randomized to a
test-and-treat strategy or prompt endoscopy. There were similar patient outcomes
at 12 months but there was a small difference in patient satisfaction in favour
of the prompt endoscopy strategy.13
Table 5. Summary of studies with follow-up on
subsequent need for endoscopy after urea breath testing
RDB = randomized double-blind; GP = general practice;
Hosp = hospital
*These studies were randomised trials of test-and-treat vs prompt endoscopy but the test-and-treat arm was not double-blinded. Patients knew the results of the urea breath test and eradication treatment was given open label. †A randomized, double-blind trial of patients with uninvestigated dyspepsia treated by H. pylori eradication in primary care. ‡Some of these patients had barium study rather than gastroscopy – these are grouped together to give a total of 24/142 (12%). §In this study all patients had regular follow up and were offered gastroscopy on a proctocol-driven basis. Lack of improvement, any NSAID use and lack of expected response to proton pump inhibitors mandated an endoscopy. A randomized trial of a test-and-treat policy versus early
endoscopy has been reported recently from Glasgow. Patients referred for
endoscopic investigation of dyspepsia were randomized to either a UBT alone or
gastroscopy with H. pylori
testing.19 In both treatment arms eradication
treatment was given to H.
pylori-positive patients (the eradication rate was approximately 80% for
both groups); 586 patients (83%) could be reviewed at 12 months. Both patient
groups had a similar fall in dyspepsia scores. Only 8.2% of the test-and-treat
group were referred for gastroscopy over the 12-month follow-up period. Patient
satisfaction was similar in both groups. The success of this approach may
reflect the high prevalence of H.
pylori (51%) and the high rate of peptic ulcer disease in Glasgow. The
overall health resource costs for the test-and-treat strategy were less than 50%
of those of the direct endoscopy strategy.20
The only truly double-blind study (where the patients were blinded as to whether
or not eradication treatment was given) comes from
Canada.21 This trial involved 36 primary care
centres that studied 294 patients positive for
H. pylori with symptoms of dyspepsia
(patients with predominant reflux symptoms were excluded). They were given
eradication treatment or one week of omeprazole and placebo (instead of
antibiotics). At 12 months’ follow up 50% of the eradication group had no
or minimal symptoms compared with 36% of the placebo group (p = 0.02). Patients
in the eradication group had less healthcare utilisation costs in the following
year.
Economic analysis of a test-and-treat policy compared with a
direct endoscopy policy depends on a wide range of assumptions (which may be
incorrect or not transferable to another country). Decision analysis does
suggest that a test-and-treat policy is cost effective, although the savings
(compared with the direct endoscopy strategy) have been reported to be
small.22–24 The test-and-treat policy is
more cost effective in areas of higher prevalence of
H. pylori, or where there is a targeted
approach to selection of patients more likely to be
H. pylori positive (that is, selection
by place of birth, ‘ulcer-type’ symptoms, and a past history of
ulcer disease). Cost estimations from the Scottish study may be applicable to
the New Zealand practice of medicine but will only be relevant to those parts of
New Zealand with a high prevalence of H.
pylori. The prevalence of H.
pylori at which the test-and-treat is no longer cost effective will
depend on local costs, but the suggestion from many studies and reviews is that
if the prevalence of H. pylori in
patients with dyspepsia is below 25% test-and-treat is no longer the most
cost-effective strategy.21–23 Many parts
of New Zealand have a prevalence of H.
pylori below 25%.9,15 Therefore, the
results from this study can not be generalized to all areas of New Zealand and
to all groups of dyspepsia patients. It should also be emphasized that some
caution is required in the use of a test-and-treat policy for older patients
given the increasing incidence of gastric cancer with age. Decision making needs
to be individualized rather than driven by protocol. For example, a Maori man
with dyspepsia who has a family history of gastric cancer should have early
endoscopy and biopsies rather than a test-and-treat approach.
H. pylori serology
may be an adequate replacement for the urea breath test and has advantages of
convenience and lower cost. A negative H.
pylori serology test is highly predictive of the absence of
H. pylori infection. A positive
serology test is less reliable but may be an adequate test upon which to base
the decision to treat with eradication treatment. An important caveat is that if
the underlying prevalence of H. pylori
in the community is low (ie, less than 20%) then the false positive rate (PPV)
for serology becomes unacceptable. It is also very important to carefully ask
the patient about previous eradication treatment because the serology test is
often persistently positive for many years after successful eradication
treatment.
The use of the nurse practitioner as the leader of the
dyspepsia clinic was a successful innovation. The nurse practitioner quickly
developed expertise in the evaluation of dyspepsia – in particular the
ability to distinguish typical reflux symptoms from ‘ulcer-type
symptoms’, and an understanding of H.
pylori diagnostic tests and the role of
H. pylori in gastroduodenal disease.
The nurse quickly developed an understanding of the nature of non-ulcer
dyspepsia and, in particular, the role of life stresses. A consultant was always
available for advice but a significant degree of independence was possible. The
clinic is no longer functioning because of the high level of
H. pylori testing in primary care and
the widespread adoption of a test-and treat strategy in our area. The
Gastroenterology Department at Auckland Hospital continues to offer a limited
service for breath testing post-eradication of
H. pylori.
Author information:
Alan G Fraser, Associate Professor of Medicine, Department of Medicine,
University of Auckland; Susan Williamson, Project Nurse; Mark Lane, Clinical
Associate Professor, Gastroenterology Department, Auckland Hospital, Auckland;
Brian Hollis, Medical Laboratory Scientist, Microbiology Laboratory, Middlemore
Hospital, Otahuhu, Auckland
Correspondence:
Associate Professor Alan G Fraser, Department of Medicine, University of
Auckland, Private Bag 92019, Auckland. Fax: (09) 373 7677; email: a.fraser@auckland.ac.nz
References:
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