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Definition &
epidemiology
Causes of
dyspepsia
Diagnosis
Management
& referral
Prognosis
The author
Dyspepsia
DR ANNE DUGGAN,
gastroenterologist and associate
director, clinical governance,
Hunter New England Area
Health, and conjoint professor,
school of medical practice and
population health, The University
of Newcastle, NSW.
Background
DYSPEPSIA, from the Greek dys (bad)
and peptein (digest) is a common presentation in general practice and a source
of considerable morbidity and cost to
the community.
When William Brinton wrote in
1865 that dyspepsia is “not so much a
single and substantive disease as a variety of ailments ... characterised not so
much by the presence of certain symptoms as by the absence of structural
lesions” he was not to know that in
2009 his statement would have particular relevance.
In Western societies today, structural
lesions previously associated with dyspepsia, such as upper gastrointestinal
cancer and peptic ulcer disease, are far
less prevalent than in the late 19th and
20th centuries. Today, dyspepsia is more
commonly ‘dis-ease’ than a disease.
Definition
For the purposes of this review, dyspepsia is defined pragmatically as
upper abdominal or retrosternal pain,
discomfort, heartburn, nausea, vomiting or other symptoms considered
to be referable to the proximal alimentary tract.
Epidemiology
The overall incidence and prevalence
of dyspepsia is difficult to establish
because of the different definitions
used but appears to be unchanged
over recent years. This is probably
due to the ageing population and the
increasing prevalence of NSAID use
counteracting the effects of falling
prevalence of Helicobacter pylorirelated ulcers.
Other risk factors that influence
dyspepsia prevalence include:
• Smoking.
• Use of NSAIDs.
• Alcohol intake.
• Socioeconomic status.
• Obesity, particularly in relation to
gastro-oesophageal reflux disease
(GORD).1
General practice activity data estiwww.australiandoctor.com.au
mate that about 10% of patient
attendances in Australia are due to
GORD, the single most common
cause of upper GI symptoms. Estimates from these data suggest there
are more than two million Australians with GORD. We know that
only a proportion of those with dyspepsia will ever consult a GP, and
estimates from community studies in
a number of Western countries are
that up to 40% of the population
have upper GI symptoms.
Despite under-presentation to general practice, the cost to the PBS of
prescribed acid-suppression therapy
was more than $400 million, or
about 10% of our national drug
budget in 2007/08.
A US survey of 117,497 endoscopic reports involving 99,558
patients found that 43% of endoscopies were for dyspepsia and onethird of patients were under 50 and
had no alarm symptoms.1
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22 January 2010 | Australian Doctor |
17
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HOW TO TREAT Dyspepsia
Causes of dyspepsia
Peptic ulcer disease
About 5% of patients with
dyspepsia have peptic ulcer
disease. The association
between H. pylori and peptic
ulcer disease is well documented. More than 90% of
duodenal ulcers are associated
with the infection, as are a
similar proportion of nonNSAID-induced gastric ulcers.
As expected, with the fall in
prevalence of H. pylori infection there has been a marked
fall in peptic ulcer disease
prevalence. Over the 10 years
from 1970 some countries
reported an almost 10-fold
decline in hospitalisation rates
for peptic ulcer disease.
18
Table 2: Causes of H. pylori-negative peptic ulcers
Table 1: Endoscopic findings for patients with dyspepsia investigated in the
primary care setting
False-negative H. pylori diagnostic test
Findings
%*
NSAID use (recognised or unrecognised)
Normal findings
77%
Other ulcerogenic drugs
Reflux oesophagitis
15.5%
Smoking
Gastric ulcer
2.3%
Gastric hypersecretion (Zollinger–Ellison syndrome) (very rarely)
Gastric erosions
6.2%
Mucosal diseases (Crohn’s disease, lymphoma, neoplasm)
Duodenal ulcer
2.7%
Infection (CMV, herpes simplex virus)
Duodenal erosions
3.5%
Gastro-oesophageal malignancy
0.2%
Concomitant diseases (chronic renal failure, cirrhosis,
malignancy)
*Some patients had dual pathology
Figure 1: Age standardised incidence of oesophageal adenocarcinoma in NSW by gender,
1972-2005. Reproduced from Stavrou E, et al. Medical Journal of Australia 2009; 191:310-14, using NSW Central
Cancer Registry data.
Adenocarcinoma
Female
Male
JP female
JP male
Number of cases per 100,000
5
4
APC3 = 4.2%
3
2
APC1 = -6.6%
APC2 = 21.6%
APC4 = 4.3%
1
1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004
APC = annual percentage point change
JP = joinpoint analysis
Figure 2: Age-specific rates of oesophageal cancer, Australia 2001.
Source: Australian Institute of Health and Welfare.
200
160
Number per 100,000
• Transient lower-oesophageal
sphincter relaxation.
• Anatomical disruption of the
diaphragmatic sphincter.
• Free reflux across a hypotensive lower-oesophageal
sphincter.
Smoking, fats, caffeine, alcohol and a variety of drugs such
as theophylline and calciumchannel blockers decrease
lower-oesophageal sphincter
pressure and may precipitate
symptomatic reflux.
H. pylori infection is not a
cause of GORD and may even
be protective, by raising gastric pH.
Oesophageal
adenocarcinoma
0
120
80
40
0
20-24 25-29 30-34
35-39 40-44
45-49
50-54 55-59 60-64
65-69 70-74 75-79
80-84
85+
Age
Figure 3: Age-specific rates of gastric cancer Australia 2001.
GORD is a risk factor for adenocarcinoma of the oesophagus and its pre-cursor Barrett’s
oesophagus. A large study
from Sweden found patients
with oesophageal adenocarcinoma were more than seven
times more likely to have
symptomatic heartburn than
the background population.
The recent rise in the prevalence of adenocarcinoma in
Australia and elsewhere is
thought to be due to an
increase in the prevalence of
GORD (figure 1).
However, oesophageal adenocarcinoma remains a rare
cause of dyspepsia and may be
an incidental finding at
endoscopy. Figure 2 shows
age-specific
rates
of
oesophageal cancer.
Source: Australian Institute of Health and Welfare.
Adenocarcinoma of the
stomach
350
Number per 100,000
SINCE the publication of the
first Helicobacter pylori eradication trial in 1988 there has
been great enthusiasm for
attributing dyspepsia to H.
pylori infection, an enthusiasm
that was misplaced and is now
waning. It is now clear that in
most Western countries H.
pylori is responsible for only
a minority of the cases of dyspepsia. Infected individuals
have an estimated 1:4-1:10
lifetime risk of developing
ulcer disease and an increased
risk of gastric cancer.
As fewer people in the population acquire H. pylori in
their childhood, H. pyloriassociated ulcer disease is
becoming increasingly uncommon and gastric cancer is
becoming rare. In most Western countries young people are
more likely to stay uninfected
than infected with H. pylori.
In contrast, the elderly continue to carry much of the risk
of ulcer disease and the small
increased risk of gastric cancer
because a higher proportion of
them have acquired H. pylori
as a result of the poorer
domestic hygiene in their childhood.
The second reason for
attributing only a minority oof
dyspepsia cases to H. pylori is
that there is little evidence to
implicate this bacterium as a
cause for dyspepsia in the
absence of an ulcer. This is
clearly demonstrated by the
disappointing outcomes of H.
pylori eradication therapy for
GORD, gastritis and non-ulcer
dyspepsia.
As the prevalence of H.
pylori has fallen, so too has
the proportion of patients with
a lesion as a cause for their
dyspepsia. Recent endoscopic
studies demonstrate this and,
in particular, the marked
decline in the prevalence of
peptic ulcer disease and gastric cancer.
A recent study from 17
mainly Western countries
reviewed the endoscopic findings of patients aged 18-70
presenting to primary care
with dyspepsia without alarm
symptoms. Only 23% were
reported to have endoscopic
abnormalities. The most
common pathology found was
reflux oesophagitis (table 1).2
300
250
200
150
100
50
0
20-24 25-29 30-34
35-39 40-44
45-49
50-54 55-59 60-64
65-69 70-74 75-79
80-84
85+
Age
The second leading cause of
peptic ulcer disease in our
community is the use of
NSAIDs, including aspirin. A
recent meta-analysis showed
that the risk of GI complications from NSAIDs is 1.5-2%
per year in the average patient
and 10% per year in the highrisk patient. The risk of ulcer
complications from COX-2selective inhibitors is about
half that for naproxen.
It is worth noting that most
NSAID-induced erosions and
| Australian Doctor | 22 January 2010
ulcers are asymptomatic, with
GI haemorrhage often being
the first indication of an
NSAID-induced ulcer.
NSAIDS and H. pylori are
thought to induce ulcer disease
by different mechanisms but
with synergism between the
two risk factors. H. pylori
infection increases the risk of
bleeding from peptic ulceration twofold, NSAIDS fivefold
and together there is a sixfold
increase.
H. pylori-negative NSAID-
negative peptic ulcers do occur,
but true H. pylori-negative
NSAID-negative ulcers are
very uncommon and are a
diagnosis by exclusion (table
2).
Smoking increases the risk
of peptic ulcer disease in a
dose-dependent manner.
Gastro-oesophageal reflux
disease
The aetiology of GORD is
unknown but thought to
occur by three mechanisms:
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In the past, one of the main
arguments for investigating
dyspepsia was to avoid missing gastric cancer. Gastric
cancer is now known to have
a rare association with dyspepsia. In Australia the age-standardised rate of gastric cancer
is 9.7/100,000 in males, and
lower in females, with a
median age of diagnosis over
70 in both groups. As figure
3 shows, gastric cancer is rare
under the age of 50 years.
Functional dyspepsia
Functional dyspepsia is defined
as chronic dyspepsia in the
absence of a structural lesion
that may account for the
symptoms. The pathophysiology of this condition has been
poorly characterised.
Recently, Rome III, a meeting of GI experts, proposed
that functional dyspepsia be
divided into two groups: postprandial distress syndrome,
consisting of postprandial fullness and early satiety; and epigastric pain syndrome, with
more consistent and less mealrelated symptoms. While this
new classification may help
our future understanding of
the pathophysiology and ultimately lead to better treatment, its value for current
management is unclear.
A substantial proportion of
patients with functional dyspepsia also have irritable
bowel syndrome. The mechanism of both disorders may be
similar and be a clue to the
pathophysiology.
Dual pathology
It is important to recognise
that patients may have a combination of causes for dyspepsia, such as ulcer disease as
well as GORD. A patient with
peptic ulcer not improving
after H. pylori eradication may
have GORD requiring acidsuppression therapy.
Other
Drug therapy is often an
unrecognised cause of dyspepsia. Examples include NSAIDs,
digoxin, antibiotics (including
erythromycin), and iron therapy.
Ten to 20 per cent of
patients taking NSAIDs have
associated dyspepsia, with or
without an ulcer being present, and within six months of
starting NSAID therapy 515% of patients will discontinue it because of dyspepsia.
Patients taking COX-2
inhibitors such as celecoxib,
rofecoxib (withdrawn worldwide) and meloxicam have a
similar frequency of dyspepsia
to non-selective NSAIDS but
a lower risk of peptic ulcer
complications.
The contribution of biliary
pain and dysmotility to dyspepsia (including sphincter of
Oddi dysfunction) is unclear
but probably small.
Systemic disorders such as
diabetes and hypercalcaemia
may rarely cause dyspepsia.
There is debate as to
whether dyspepsia is more
common among patients with
undiagnosed coeliac disease.
The background prevalence of
coeliac disease is about one in
100 and so is not infrequently
found, including in patients
with GI symptoms.
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HOW TO TREAT Dyspepsia
Diagnosis
History
IT is important to assess the
timing of symptom onset in
relation to starting of new
medications and to ask about
alcohol and cigarette consumption. Specific questioning about weight loss, dysphagia, symptoms resistant to
acid-suppression therapy,
early satiety, melaena and
haematemesis are essential to
evaluate the likelihood of
upper GI malignancy.
A dietary history of known
precipitants of GORD may
be very important for future
management, as stopping
excessive consumption of caffeine, chocolate, alcohol or
fatty and spicy food may be
sufficient to prevent further
symptoms.
A history of predominant
heartburn or reflux is useful
for the diagnosis of GORD.
However, up to one in five
patients are unable to decide
on their most bothersome
symptom.
A variety of respiratory
and laryngeal symptoms has
been attributed to GORD.
These include cough, wheeze,
and hoarse voice or sore
throat, and may occur in the
presence or absence of dyspepsia. Water brash (stimulation of salivation by the presence of gastric acid in the
lower oesophagus) also rarely
occurs. Dysphagia and
odynophagia may result from
altered oesophageal peristalsis, stricture or increased sensitivity. These symptoms
should be treated with potent
acid-suppression therapy, but
the response is often slow and
may be poor.
Despite traditional teaching, the clinical diagnosis of
peptic ulcer disease is difficult.
Fewer than 25% of ulcers are
diagnosable on history. The
accuracy of clinical diagnosis
can be increased by considering risk factors (table 3).
Family history is a risk
factor for peptic ulcer disease,
with twin studies showing
this to be due to both genetic
and environmental factors.
Smoking and a history of
pain on an empty stomach
have been shown to increase
the likelihood of ulcer disease
as the cause of dyspepsia.
In the elderly, a history of
aspirin and NSAID consumption is particularly important.
The risk for NSAID complications increases with
advanced age, H. pylori infection, smoking, previous ulcer
history, concurrent anticoagulant and prednisone use.
SSRIs also slightly increase
the risk of peptic ulcer disease. Comorbidities such as
cardiac failure and diabetes
increase the risk of peptic
ulcer bleeding.
The importance of a past
history of peptic ulcer disease
cannot be sufficiently emphasised. A recent survey in a
NSW hospital found that
85% of patients admitted
20
Table 3: Clues to peptic
ulcer disease as a cause
for dyspepsia
Table 4: Investigation of dyspepsia
Past history of peptic ulcer disease
Family history of peptic ulcer
disease
Strategy
Advantages
Disadvantages
Empirical therapy
Diagnostic of acid-related disorder;
does not require specialist referral
Does not cure peptic ulcer disease; adequate patient/GP
reassurance?; misses the rare early malignancy
Gastroscopy
Diagnosis of curable disease;
diagnosis of H. pylori infection;
patient reassurance
Expensive; poorly predictive of response to acidsuppression therapy; inconvenient; results often normal
H. pylori test
and treat
Cures H. pylori-associated disease;
does not require specialist referral
Requires access to ‘good’ H. pylori diagnostic methods;
unnecessary exposure to antibiotics; promotes
antibiotic resistance; adequate patient/GP reassurance?
H. pylori test
and refer
Selective treatment of H. pyloriassociated disease
Misses H. pylori-negative peptic-ulcer disease; requires
access to ‘good’ H. pylori diagnostic methods;
adequate patient/GP reassurance?
Smoking
Periodicity of symptoms
History of pain on an empty
stomach
Use of NSAIDs, SSRIs, COX-2
inhibitors, prednisone
Table 5: Advantages and disadvantages of different tests for H. pylori diagnosis
ENDOSCOPIC TESTS
Advantages
All
Microbial culture
Histology
Urease test
• Useful pre- and post-treatment
• High specificity
• High specificity
• High specificity
• Allows determination of
• Permanent record
• Rapid
• Inexpensive
antibiotic resistance
Disadvantages • Expense of endoscopy
• Sampling-error-dependent
sensitivity
• Time consuming
• Preparation dependent
• Observer dependent
• Does not allow determination
of antibiotic resistance
Does not allow determination of
antibiotic resistance
NON-INVASIVE TESTS
Advantages
All
Urea breath test
Serology
Rapid serology
(near-patient tests)
Non invasive
• High sensitivity and specificity
• Can confirm efficacy of
•
•
•
•
•
•
•
•
eradication using 13C testing
• Can be performed at
a distance from the centre
performing the analysis
Disadvantages • No diagnostic information on
H. pylori-induced disease
• Do not allow determination
of antibiotic resistance
with a past history of peptic
ulcer disease denied previous
treatment with H. pylori eradication therapy and had positive H. pylori serology indicative of ongoing infection.3
These patients should be
offered H. pylori eradication
therapy without further
investigation. The benefits are
threefold:
• A substantially reduced
ulcer risk with or without
NSAIDS.
• Improved quality of life for
those who become asymptomatic.
• Savings from avoided treatment.
Trial of acid-suppression
therapy
For most patients a trial of
acid-suppression therapy is
usually diagnostic of an acidrelated disorder and is safe.
Rapid symptom recurrence
on stopping acid-suppression
therapy is virtually diagnostic of GORD. Patients should
be advised to present again if
symptoms do not resolve following 2-4 weeks of acid-suppression therapy
Gastroscopy
Gastroscopy is indicated if
malignancy is suspected
because of the presence of
alarm symptoms such as
weight loss, dysphagia, early
satiety,
haematemesis,
melaena, anaemia and bloody
stools, or if dyspeptic symptoms are unresponsive to 2-4
| Australian Doctor | 22 January 2010
• 13C urea and isotope ratio mass
spectrometry are expensive
Endoscopic
diagnosis is
unnecessary for
most patients
with dyspepsia.
Inexpensive
Quick
Easy to perform
Requires no specialised
equipment
• Need local validation — accuracy
depends on purification of strains
and suitability of strain types for
group being tested
weeks of acid-suppression
therapy. Gastroscopy in the
latter instance should be performed after PPIs have been
ceased.
Early investigation — why
not initial endoscopy?
Endoscopic diagnosis is
unnecessary for most patients
with dyspepsia because of its
low yield, particularly in
those under 50 (table 4). The
most frequent abnormal finding at endoscopy is erosive
oesophagitis, which responds
to empirical therapy, making
endoscopy unnecessary.
Fewer than 50% of patients
with GORD have endoscopic
evidence of oesophagitis.
Multiple studies have
shown that few treatable cancers are detected by early
endoscopy. A recent large
study in primary care in 17
mostly Western countries
provides a useful summary of
the role of endoscopy in diagnosing cancer in countries
like Australia.2 In this study
2741 patients aged 18-70
with dyspepsia and without
alarm symptoms had
endoscopy. Upper GI cancer
was found in two per 1000
patients (0.22%).
The authors concluded that
if endoscopy were limited to
only dyspeptic patients 50
years and over, one
oesophageal cancer and no
gastric cancer would have
been missed. If endoscopy
cost $500 it would cost about
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Inexpensive
Quick
Easy to perform
Requires no specialised
equipment
• Need local validation
• Operator dependent
$82,900 (between $35,714
and $250,000) to detect that
2
cancer.
Up to 40% of patients
diagnosed with oesophageal
adenocarcinoma have no
prior history of dyspepsia.
Endoscopy has had little
impact on gastric cancer survival because most cancers
are advanced when diagnosed
and treatment options are
limited. Current five-year survival for gastric cancer is
25% compared with 58% for
cancer overall and 61% for
colonic cancer. As 37% of
oesophageal adenocarcinoma
in Australia is attributable to
poor physical activity and
obesity, the logical management strategy for its prevention is promoting exercise
and appropriate dietary
intake.4
Advocates of endoscopy
argue that initial empirical
therapy may miss Barrett’s
oesophagus. The risk of Barrett’s oesophagus increases
with duration of reflux and is
least likely to be found at the
time of onset of symptoms.
It is important to distinguish
endoscopy before starting
acid-suppression therapy from
endoscopy after a trial of acidsuppression therapy. A study
of the effect of time between
withdrawing PPIs and gastroscopy showed a greater
diagnostic yield the longer the
time gap. A course of PPI therapy will heal more than 60%
of peptic ulcers in two weeks
and 94% within a month.
PPIs should be stopped for at
least four weeks before
endoscopy is performed.
H. pylori testing
H. pylori testing and eradication should be offered to
patients with peptic ulcer disease or those starting NSAID
therapy, as it is of proven
benefit for these conditions.
The yield from H. pylori testing has fallen as a result of
its decreasing prevalence.
The main methods for
detecting H. pylori are shown
in table 5. Serology remains
the most readily available,
inexpensive and accurate test
for detection. To confirm
eradication, the urea breath
test is the best non-invasive
option, as serology may
remain positive for up to 12
months.
pH monitoring
pH monitoring involves
inserting a pH probe into the
distal oesophagus and recording of the proportion of time
pH falls below 4 over a 24hour period. It has a limited
role in the diagnosis and
management of dyspepsia but
can be useful to assess the
adequacy of therapy if a
patient is still symptomatic
on maximal acid-suppression
therapy, or, off therapy, to
assess symptom correlation.
Patients can have GORD
symptoms despite a normal
pH study.
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Management
UNDERSTANDING why people
present may be the key to effective
management. An Australian population-based survey found that only
56% of people with dyspepsia had
ever consulted about their symptoms.
Consultation seems not just related
to age or the severity or duration of
symptoms, but also to more complex issues such as anxiety, including fear of serious disease and stressful life events. Patients concerned
about the possibility of cancer are
unlikely to have symptom resolution
without appropriate counselling.
Remove the cause
It is important to see the patient’s
current symptoms in the context of
their overall health.
It is therefore logical to address
lifestyle factors known to promote
dyspepsia and to impact on health
in general by taking a comprehensive dietary and drug history and
providing appropriate counselling
(table 6). Frequent dietary components associated with reflux include
coffee, orange juice, alcohol and
fatty and spicy foods.
Patients with suspected reflux
should also be advised to avoid
eating large meals just before going
to bed and to avoid tight-fitting
clothes after meals. A wedge pillow
or elevation of the head of the bed
can help to reduce nocturnal symptoms. Up to 20% of patients will
respond to lifestyle intervention
alone.
NSAID therapy should be
reviewed and stopped if possible.
Patients in the high-risk group for
peptic ulcer complications should
be offered concurrent proton-pump
inhibitor therapy and be prescribed
the least-toxic NSAID (either
ibuprofen or diclofenac), unless they
are also high risk for cardiovascular
disease, in which case NSAIDs
should be avoided, or, if an NSAID
is needed, naproxen with a PPI is
the preferred choice. Consensus
guidelines for management with
NSAIDs are now well established
(figure 4).5
It is clear that patients who are
H. pylori positive are at higher risk
of NSAID-associated ulcer complications and that H. pylori eradication before starting NSAIDs reduces
that risk. The data on eradication
after an NSAID ulcer complication
has occurred are less clear.
Another group of patients of particular concern are those with coronary artery stents who are often
receiving aggressive antithrombotic
therapy with both aspirin and clopidogrel to prevent stent blockage.
The GI bleeding risk increases with
the number of antithrombotic
agents used. Clopidogrel synergistically causes GI bleeding in patients
using aspirin, non-selective NSAIDs
or anticoagulants and increases the
blood loss caused by NSAIDs.
There has been recent concern
over whether PPIs decrease effectiveness of clopidogrel if concomitantly prescribed. In November
2008 the American Heart Association, the American College of Cardiology and the American College of
Gastroenterology issued a joint
statement concluding that there was
no definite evidence to justify changing clinical practice. A clinical trial is
under way to provide more data.
Figure 4: Algorithm for managing patients requiring NSAIDs.
Table 6: Modifiable
dyspepsia-related risk factors
Drugs, eg, NSAIDs, COX-2
inhibitors
Patient
requires
NSAIDs
Smoking
Excess alcohol
High fat intake
Obesity
Hi GI risk
Large meals
Low GI risk
Low fruit intake (may be a factor)
Source: Rostom, 2009.5
Hi CV risk
(on aspirin)
Avoid NSAID
if possible
Can’t avoid
NSAID
Very high CV risk is
primary concern
Naproxen + PPI
Acid-suppression therapy
A proportion of patients will
respond to an initial 1-2-week trial of
acid-suppression therapy without further need for medication, at least for
a number of months. A single daily
standard dose of a PPI results in a
gastric pH >4 about 67% of the time
and is sufficient for most patients
requiring daily therapy, with a few
requiring a twice-daily dose.
Others can be well controlled with,
and may prefer, ‘on demand’ therapy with acid-suppression therapy or
antacids. On-demand therapy has
been shown to be effective for a large
proportion of patients with GORD,
with similar levels of patient satisfaction to those taking regular acid-suppression therapies.
For patients with evidence of
oesophagitis on endoscopy, severity
of disease can determine treatment
needs. Patients with severe
oesophagitis are more likely to
develop local complications such as
stricturing and bleeding. They should
be maintained on PPI therapy to
avoid these complications.
The expected success rates for
medical treatment of GORD vary
widely. Recognised approaches, from
the most successful to the less successful, are as follows:
• Increased daily dose PPI (100%
success).
• Single daily dose PPI (80%).
• Cisapride (50%).
• H2-receptor agonists (50%).
• Antacids (20%).
• Lifestyle modification (20%).6
There are few data showing a
step-down approach to be more cost
effective than a strategy of targeting
therapy to symptoms.
Prokinetic therapy may be useful
for patients with dyspepsia unresponsive to acid-suppression therapy.
Options include domperidone and
metaclopramide.
Treatment for functional dyspepsia
is difficult. Initial therapy should
comprise acid suppression, with sub-
Low CV
risk
High CV risk
(on aspirin)
Low CV
risk
COX-2 alone or
traditional
NSAID + PPI
Naproxen
+ PPI
Traditional
NSAID
Very high GI risk is
primary concern
Cox-2 + PPI
GI = gastrointestinal
PPI = proton-pump inhibitor
CV = cardiovascular
sequent use of prokinetic agents, antispasmodics, antidepressants and
behavioural therapy or psychotherapy considered for resistant symptoms.
Is long-term acid-suppression
therapy safe?
Postmarketing surveillance data for
use of H2-receptor antagonists compared with community controls show
them to be relatively safe. Long-term
postmarketing surveillance data for
PPIs are not yet available despite the
first PPI being released in 1988.
The most common side effects of
PPIs are headache and diarrhoea and
they are uncommon. Other rarer but
serious reported side effects are interstitial nephritis, which is not always
reversible and, hypomagnesaemia.
PPIs act by reducing gastric acid
production. Reduced gastric acid promotes the growth of enteric and swallowed flora in the proximal gut and
leads to a small increased risk of community-acquired pneumonia and of
enteric infection.
An acid environment is also needed
for calcium absorption, and longterm PPI use may predispose to osteoporosis-associated hip fracture. The
medications appear to be safe in pregnancy.
cation strategy is based on the principle that H. pylori eradication will
cure non-NSAID ulcer disease, and
acid-suppression therapy most of the
remainder.
Antibiotic intolerance, side effects
and the impact of inappropriate use
of antibiotics on community antibiotic resistance are some of the disadvantages of H. pylori-eradicationbased strategies.
A meta-analysis of H. pylori-eradication studies in patients with nonulcer dyspepsia concluded that H.
pylori eradication therapy has a small
but statistically significant effect in H.
pylori-positive non-ulcer dyspepsia.
The number needed to treat to cure
one case of dyspepsia was 14. The
number needed to harm was not calculated.7
The benefits of secondary prevention of gastric cancer through H.
pylori eradication are theoretical,
although biologically plausible, but
there are no data to indicate optimal
time for treatment to be effective.
It is reasonable to offer H. pylorieradication therapy to patients with
dyspepsia and a family history of gastric cancer, as a history of a firstdegree relative with gastric cancer
increases the risk threefold.
Treatment of H. pylori
Which H. pylori treatment
option?
Two H pylori-post-testing treatment
strategies have been recommended:
• H. pylori-negative patients:
treatment with a PPI.
• H. pylori positive patients: either
— referral for endoscopy, or
— H. pylori eradication treatment,
with subsequent referral only of
those who have persistent symptoms after a trial of acid-suppression therapy (see table 4).
The strategy of referral for
endoscopy is based on the association between H. pylori infection and
peptic ulcer and gastric cancer, and
increases the diagnostic yield of selective endoscopy. The H. pylori eradi-
For H. pylori infection the main
issues surrounding treatment are
which regimen to use and whether
eradication of infection needs to be
confirmed.
Controversy remains as to the preferred combination of antibiotics to
use for eradication therapy. PPI-based
therapies have been shown to have a
higher efficacy and to be better tolerated than bismuth-based therapies.
The main PPI-based combination
packs are Nexium Hp7 and Klacid
Hp7, seven-day regimens of twicedaily clarithromycin 500mg, amoxycillin 1g and esomeprazole 20mg or
omeprazole 20mg.
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In the event of allergy or resistance
to either of these antibiotics, a second
prescription for metronidazole 400mg
twice daily can be written and the
offending antibiotic substituted.
All regimens involve antibiotics to
which H. pylori has been demonstrated to develop resistance. Australian studies show resistance for
clarithromycin is about 6%. In vitro
metronidazole resistance has been
shown to be up to 40%.
The need to confirm the success of
eradication therapy has been questioned because of the high efficacy of
eradication therapies and the cost
involved detecting few failures. A
pragmatic approach is to confirm
eradication for patients who have had
complicated ulcer disease, and who,
because of comorbidity, would poorly
tolerate ulcer complications.
Options to detect failed eradication
are limited to endoscopic methods
(which are invasive), and urea breath
testing. There is a prolonged antibody
response to infection, making serology unhelpful.
Patients failing H. pylori eradication can be referred to a gastroenterologist to determine the most
appropriate antibiotic combination
or for consideration of H. pylori culture and sensitivities, if the initial indication for H. pylori eradication was
justified. After eradication, the risk
of re-infection is small (of the order of
0.5-1% per annum).
In the absence of aspirin or NSAID
use, eradication therapy virtually
cures H. pylori-associated peptic
ulcer disease without any further
treatment. After successful eradication, about 5% of ulcers recur over a
6-12-month period, compared with
25% of those given H2-receptor
antagonists, and just under 75% of
those untreated.
It needs to be remembered that a
proportion of patients will have concurrent GORD and may therefore
need treatment for this.
Anti-reflux surgery
Effective acid-suppression therapy
has meant that surgery is rarely indicated for ulcer disease except in the
presence of complications. Indications for anti-reflux surgery (fundoplication) include:
• Refractory reflux disease or
oesophagitis.
• Recurrent oesophageal strictures.
• Recurrent aspiration due to
GORD.
• Recurrent bleeding from either
oesophageal or associated gastric
(Cameron’s) ulcers.
Up to 80-90% of patients have
good to excellent outcomes at 10 or
more years. Laparoscopic fundoplication has less short-term morbidity
than open surgery.
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HOW TO TREAT Dyspepsia
from previous page
Psychological interventions
Despite reports of benefits for both
psychotherapy and hypnotherapy for
functional dyspepsia, this is not confirmed in formal studies.
Meeting patient expectations
Some patients are dissatisfied out of
proportion to their residual symptoms
after treatment. A major cause of dissatisfaction is unmet expectations. A
US survey of patients visiting primary
care physicians for various reasons
found 98% had at least one pre-visit
expectation.8 The most frequent expectations were:
• A diagnosis (81%).
• An estimate of how long the symptom would last (63%).
• A prescription (60%).
• A diagnostic test (54%).
• A subspecialty referral (45%).
Resurvey immediately after their
visit found the most common unmet
expectations were prognostic information (51%) followed by diagnostic
information (33%). Of note, patients
with no unmet expectations had less
worry about serious illness (54% vs
27%), significantly greater satisfaction
(59% vs 19%) and were more likely to
have symptom alleviation.
A study of 91 patients starting PPI
therapy for gastro-oesophageal reflux
symptoms found that patients
expected:
• Improvement (61%).
• Return to normal daily life (46%).
• Improved quality of life (44%).
• No further treatment after the initial
treatment (36%).
• For the PPI to have no side effects
(34%).
• Elimination of symptoms (33%).9
Only four patients had no real expectations of the medication.
There are clearly common themes in
regard to what patients want to know
and most patients want to be involved
in their care.
Who and when to refer
All patients with alarm symptoms and
those who, on clinical grounds, are
suspected of having peptic ulcer disease should be referred for endoscopy
before acid-suppression therapy. It is
also not unreasonable to refer the elderly patient with new-onset dyspepsia
The future
Prognosis
in the absence of a medication change.
Whether to refer the patient with
longstanding symptoms of GORD for
screening for Barrett’s oesophagus
remains controversial. The higher-risk
group are male smokers with longstanding and severe symptoms. If
referred for surgery, these patients
should be fit enough for the procedure.
The largest referral group will be those
who have not responded to high-dose
acid-suppression therapy, and these can
be the most difficult group to treat.
A major role for the gastroenterologist is to exclude other pathology and
to document oesophageal acid exposure by pH testing. For some patients,
concern about the significance of their
symptoms may only be allayed by
referral to a specialist.
References
Available on request from
julian.mcallan@reedbusiness.
com.au
Online resources
• Gastroenterological
Society of Australia:
www.gesa.org.au/pdf/
Healthy_Gut_2nd_03.pdf,
www.gesa.org.au/pdf/
Heartburn_3Ed_07.pdf,
www.gesa.org.au/pdf/
H_Pylori_2nd_03.pdf
Summary
• Dyspepsia is commonly due to GORD or functional symptoms and
Does dyspepsia get worse over time?
GORD
THE natural history of GORD is not well
documented. Most data come from
patients with symptoms severe enough to
warrant referral to secondary care. Some
community-based longitudinal studies
report a steady prevalence, with the proportion of affected individuals having
symptom resolution being matched by a
similar proportion becoming symptomatic.
These studies also report “poorer quality of
life”. A systematic review of patient outcomes for GORD found 40% of those
taking prescription medications reported
residual symptoms.10
SEVERAL endoscopic anti-reflux techniques are under evaluation and may
obviate the need for surgery in people
with severe GORD. This is unlikely to
have a major impact at a population
level.
In contrast, the rise in obesity — a
risk factor for reflux — may result in a
substantial rise in the number of consultations for GORD in the future and
in turn the incidence of oesophageal adenocarcinoma. Whether the fall in H.
pylori prevalence can be implicated in
these events remains to be determined.
rarely due to upper GI malignancy.
• Acid-suppression therapy is both a diagnostic and therapeutic
strategy for most patients with dyspepsia.
• Patients should be questioned about alarm symptoms and referred
for endoscopy if any are present.
• For patients with uncomplicated GORD, therapy should be tailored
to achieve symptom control.
• Endoscopy should be considered for patients who fail to respond
to acid-suppression therapy.
• H. pylori testing and eradication should be offered to patients with
peptic ulcer disease or those starting NSAID therapy, as it is of
proven benefit for these conditions.
A guide to the management of dyspepsia
Peptic ulcer disease
Dypepsia history:
• Alarm symptoms
• Peptic ulcer disease risk factors
H. pylori eradication virtually cures duodenal ulcer disease, with relapse rates at one
year of about 5%. Without treatment, about
40% of duodenal ulcers and about 30% of
gastric ulcers heal at four weeks, but 5080% recur in the subsequent 6-12 months.
It is controversial whether recurrences continue indefinitely.
No
Yes
• Remove risk factors
• Lifestyle modification
• Acid-suppression therapy according to
symptom severity
• Consider other diagnoses
Endoscopy
Functional dyspepsia
Functional dyspepsia has a high placebo
response of up to 50%, consistent with a
generally good prognosis for this disorder.
Longitudinal studies of functional dyspepsia
that have followed patients for more than a
decade show a large amount of overlap with
IBS and a high rate (up to 40%) of change
of predominant symptomatology from the
upper to lower gut, and vice versa.
Carcinoma
Peptic ulcer
Response
No cause found
Yes
No
H. pylori testing
Refer
Treat
Continue current management
Endoscopy
Author’s case study
MR RL, 52, has been troubled by knee pain not responsive to intermittent paracetamol. He recently started a
“health kick” because a friend
of similar age suffered a fatal
MI. He presented to a colleague 10 days ago because
his knee pain was limiting his
weight-loss program. He is
100kg and 165cm. He was
prescribed indomethacin but
found he developed nausea,
upper abdominal pain, burning and intermittent belching.
He comes to you requesting
treatment for his abdominal
symptoms. He reports he has
previously been well although
has not had a check-up for
years. He has a family history
of ischaemic heart disease and
peptic ulcer disease. He
smokes 20 cigarettes a day
and, with his job involving the
entertainment of clients,
drinks 50-60g of alcohol daily.
22
He is taking no regular medications.
Author comments
Mr RL’s dyspepsia follows the
prescription of an NSAID for
his knee pain and, if caused by
it, should resolve on stopping
the medication. His dyspepsia
may or may not be due to an
acute ulcer. NSAID-induced
ulcers can occur acutely and
are often silent. RL has risk
factors for ulcer disease, being
a smoker of 20 a day and
having a positive family history
for ulcer disease.
The diagnosis is relevant if
he is to continue an NSAID,
but the first question is whether
he needs an NSAID. He
requires a step-up approach to
the management of his knee
pain, including modification of
lifestyle factors, and if medication is required, this should
start with regular paracetamol.
| Australian Doctor | 22 January 2010
NSAID-induced
ulcers can occur
acutely and are
often silent.
Non-weight-bearing exercise
such as swimming may help
achieve his goal of weight loss
without exacerbating his knee
pain. If these measures fail, he
will need an NSAID and this
should be one with the least GI
toxicity, such as ibuprofen or
diclofenac, if he has a low risk
for cardiovascular events.
A COX-2 inhibitor has no
advantages in terms of symptoms, as it is associated with a
similar amount of dyspepsia.
He can reduce his ulcer risk
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and improve his cardiovascular
risk profile by stopping smoking.
It is important at this stage
to assess his cardiovascular risk
factors, in particular his blood
pressure, lipid profile and
blood sugar level, all of which
may improve with successful
weight loss. However, if he
does fall into the classification
of high risk of cardiovascular
disease (>15% risk of a major
cardiovascular event in the
next five years), he will need
to start aspirin.
In that case he should have
his H. pylori serology tested
and, if positive, be offered
treatment before starting
aspirin. Your choice of
NSAID, if required, would
then be guided by his greater
need for cardiovascular protection, and naproxen with a
PPI would be the better choice
of NSAID.
Practice points
• Establish patient drivers
for presentation.
• Address lifestyle factors
contributing to dyspepsia.
• Check for alarm
symptoms.
• Reassure patients about
the good prognosis for
dyspepsia.
• Use endoscopy
selectively.
• Consider H. pylori testing
when there is a history of
peptic ulcer disease or
when starting an NSAID.
• Assess both
cardiovascular and GI risk
when considering NSAID
therapy.
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HOW TO TREAT Dyspepsia
GP’s contribution
DR CAROLYN BLOCK
Rose Bay, NSW
Case study
IN many patients’ minds, a
medication that is available
over the counter is not truly a
medication and hence not
worth mentioning.
James requested I see his
mother as a patient, as he was
not happy with the care she
had been receiving. Mary came
to see me, an obese 77-yearold with severe OA who had
had bilateral knee replacements
and postoperative complications requiring two further
operations on the left knee.
She had an antalgic gait,
required a stick to walk, and
her mobility was extremely
limited. She was taking COX2s and Di-Gesic for pain relief,
an SSRI for depression and
Panadeine Forte when the pain
was very severe. She denied
any other medications even
with specific questioning about
over-the-counter ones.
On her second visit, for
review of blood tests I had
organised, she excused herself
after belching and reached into
her bag, popping an antacid
into her mouth. After I asked
her about this antacid use , its
frequency and any other
symptoms she had experienced, she stated that it was
just the “normal” amount of
heartburn she had on a daily
basis and was “nothing to
worry about”, as it had “been
this way for years”.
Endoscopy showed grade-4
reflux oesophagitis with Barrett’s oesophagus. PPIs were
prescribed and Mary is now
pain free. She can’t believe she
put up with the pain for so
long!
Questions for the author
What effects — both positive
and negative — do you feel
out a past history of peptic
ulcer disease.
will occur because of these
medications (ranitidine and
diclofenac) being available
OTC?
Clearly both drugs are effective for some symptoms, otherwise they would quickly go
off the shelf/market. Both have
a role and are quite effective
for patients with mild, rapidly
responding symptoms.’
The risks are when people
avoid appropriate treatment
of symptoms that do not
resolve with a trial of these
drugs, or when NSAIDs are
self-prescribed by patients
with severe comorbidities such
as heart disease with or with-
As many people now turn to
‘natural’ therapies, can you
comment on the efficacy of the
use of aloe, slippery elm, apple
cider vinegar, orange peel
extract and marshmallow
root?
There is no evidence for any
of these treatments for dyspepsia.
Feedback I received from
our drug information service
for interest is as follows.
Oral aloe vera is a popular
treatment for a variety of GI
disorders (improves colonic
bacterial activity, GI pH, stool
specific gravity and GI motility) and may be effective for
diarrhoea-predominant irritable bowel syndrome and ulcerative colitis. However, there is
no evidence for use in dyspepsia
Based on traditional evidence, slippery elm is taken
internally to relieve the symptoms of gastritis, acid dyspepsia, gastric reflux, peptic ulcers,
IBS, and Crohn's disease. Currently, clinical research is not
available to determine the
effectiveness of slippery elm in
these conditions; anecdotally
the treatment appears to be
successful and patients report
rapid improvement in upper
GI symptoms.
A search of available
resources failed to located evidence for the use of apple cider
vinegar in GI disorders.
Oral orange peel extract is
used for dyspepsia, GI disturbances, duodenal ulcers and
constipation. However, there
is insufficient reliable information about its effectiveness in
these conditions.
Traditionally, marshmallow
root has been used internally
for the treatment of inflammation of gastric mucosa, diarrhoea, peptic ulcers and constipation. Again, however, there
is insufficient reliable information available to rate its effectiveness for these conditions.
You mentioned the inhibition
of calcium absorption and
hence increased risk of osteoporotic hip fracture. Will regular blood tests help to determine who is at greater risk?
Do you suggest calcium supplementation for most patients
on PPIs?
The data are that PPIs may
predispose to osteoporosisassociated hip fracture. As
osteoporosis and hip fracture
is such a public health issue in
our community, particularly
among the elderly, I would recommend that all patients be
given advice about appropriate preventive strategies to
reduce the risk of these conditions, particularly adequate
calcium intake, weight-bearing
exercise and not smoking.
In terms of blood tests I
think there should be a high
index of suspicion for coeliac
disease, which affects about
one in 100 of the population
and, if untreated, can be associated with calcium malabsorption. If coeliac disease is a
possibility, a transglutaminase
antibody test (TGA IgA/IgG)
should be ordered.
INSTRUCTIONS
How to Treat Quiz
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Dyspepsia — 22 January 2010
1. Which THREE of the following statements
are correct?
a) Dyspepsia includes upper abdominal or
retrosternal pain, discomfort, heartburn,
nausea, and vomiting
b) Gastro-oesophageal reflux disease (GORD) is
an uncommon cause of upper gastrointestinal
symptoms
c) Risk factors for dyspepsia include smoking,
use of NSAIDs, alcohol intake, socioeconomic
status, and obesity
d) GI alarm symptoms include anaemia, melaena,
bloody stools, dysphagia, jaundice, early
satiety, weight loss, and symptoms resistant to
acid-suppression therapy
2. Which TWO of the following statements are
correct?
a) Patients infected with Helicobacter pylori have
a 10-25% lifetime risk of developing peptic
ulcer disease, and are at an increased risk of
gastric carcinoma
b) The rates of infection with H. pylori in children
and adolescents are decreasing
c) Eradication of H. pylori in the absence of an
ulcer resolves dyspeptic symptoms
d) In Western countries H. pylori infection is the
most common cause of dyspepsia
3. Which TWO of the following statements are
correct?
a) Of patients with dyspepsia and no alarm
symptoms who have an endoscopy, >70% will
have normal endoscopic findings and about
15% will have reflux oesophagitis
b) 90% of duodenal ulcers and non-NSAID-
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induced gastric ulcers are associated with H.
pylori infection
c) Dyspepsia is a symptom associated with most
NSAID-induced gastric erosions and peptic
ulcers
d) Smoking is no longer regarded as a risk factor
for peptic ulcers
4. Which TWO of the following statements are
correct?
a) GORD is thought to result from acid reflux
across a lax lower-oesophageal sphincter
b) Calcium-channel blockers increase the tone of
the lower oesophageal sphincter
c) H. pylori may protect against GORD by raising
gastric pH
d) Smoking, fats, caffeine and alcohol are not
associated with GORD
5. Which THREE of the following statements
are correct?
a) GORD is a risk factor for adenocarcinoma of
the oesophagus and its precursor Barrett’s
oesophagus
b) Oesophageal cancer is a rare cause of
dyspepsia
c) Gastric cancer is commonly associated with
dyspepsia
d) Functional dyspepsia is defined as chronic
dyspepsia in the absence of a structural lesion
that may account for the symptoms
6. Which TWO of the following statements are
correct?
a) The urea breath test is a specific and sensitive
non-invasive test for H. pylori that also provides
information on the presence of ulcers
b) Antibiotic resistance has been identified for
combination therapies against H. pylori
c) Persistent dyspepsia after H. pylori eradication
in patients with a peptic ulcer may indicate
dual pathology
d) Patients taking COX-2-selective inhibitors have
a lower frequency of dyspepsia and peptic
ulcer complications compared with nonselective NSAIDs
7. Which TWO of the following statements are
correct?
a) Peptic ulcer disease may be associated with
cough, wheeze, hoarse voice or sore throat
b) Drugs associated with dyspepsia include
NSAIDs, COX-2-selective inhibitors,
prednisone, antibiotics and SSRIs
c) Clues to peptic ulcer disease include past or
family history of peptic ulcer disease, smoking,
periodicity of symptoms, history of pain on an
empty stomach, and use of NSAIDs, SSRIs or
COX-2 inhibitors
d) For patients with a high GI risk and a low
cardiovascular risk who require an NSAID,
naproxen is the recommended treatment
8. Which TWO of the following statements are
correct?
a) For patients with a high GI risk and a high CV
risk who require an NSAID, naproxen with a
PPI or COX-2 inhibitor with a PPI are the
recommended treatments
b) For those with a low GI risk and a low CV risk
who require an NSAID, a COX-2-inhibitor is the
recommended treatment
c) Patients with coronary artery stents who are
receiving aspirin and clopidogrel are not at
increased risk of GI bleeding
d) Rapid symptom recurrence on stopping acidsuppression therapy is virtually diagnostic of
GORD
9. Which TWO of the following statements are
correct?
a) Gastroscopy is indicated if malignancy is
suspected or dyspeptic symptoms are
unresponsive to acid-suppression therapy
b) On-demand therapy is ineffective compared
with regular acid-suppression therapies for
most patients with GORD
c) Patients with severe oesophagitis should be
maintained on PPI therapy to avoid
complications
d) Lifestyle modification or simple antacids are as
effective as single daily dose PPIs in the
management of GORD
10. Which TWO of the following statements
are correct?
a) Few treatable upper GI cancers are detected
by early endoscopy in patients with dyspepsia
b) Endoscopy after a trial of acid-suppression
therapy has a greater diagnostic yield than
endoscopy before or during acid-suppression
therapy
c) H. pylori-negative patients with dyspepsia
should have an endoscopy before treatment
with a PPI
d) H. pylori-positive patients should always be
referred for an endoscopy before being given
pharmacotherapy
CPD QUIZ UPDATE
The RACGP now requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2008-10 triennium. You
can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post
or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
HOW TO TREAT Editor: Dr Giovanna Zingarelli
Co-ordinator: Julian McAllan
Quiz: Dr Giovanna Zingarelli
NEXT WEEK Abdominal aortic aneurysms (AAAs) are silent time bombs, but the treatment of AAAs is not what it used to be — in particular, recent advances in endovascular surgery have dramatically
lowered the associated morbidity and mortality of elective aortic surgery. The next How to Treat focuses on detecting and managing AAAs. The authors are Dr Dom Simring and Dr Steven Dubenec, both of
Royal Prince Alfred Hospital, and Vascular Associates Camperdown, NSW.
24
| Australian Doctor | 22 January 2010
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