The Effects of Using the Nursing Clinical
Guideline in Treating Aphthous Stomatitis
Background 1.1
Recurrent Aphthous Stomatitis (RAS) are also
known as canker sores, and this condition is one
of the most common oral mucosa inflammatory
ulcerative diseases worldwide. The aphthous ulcer
condition is characterised by localised, shallow,
rounded, painful, small, clean borders, a
peripheral erythematous halo, and a yellow or
grayish base.
(Porter SR, Hegarty A, Kaliakatsou F, Hodgson TA, Scully C. Recurrent aphthous stomatitis. Clinics in
Dermatology. 2000;18:569-78; Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Critical
Reviews in Oral Biology & Medicine. 1998;9:306–321; Ship JA, Chavez EM, Doerr PA, Henson BS,
Sarmadi M. Recurrent aphthous stomatitis. Quintessence International. 2000;31:95-112.)
Background 1.2
Aphthous ulcers are painful sores
that can occur anywhere inside the
mouth including the skin covering
the inside of the lips and cheeks, the
floor of the mouth, the tip or
underside of the tongue, the soft
palate, and the tonsilar areas. (Field EA,
Longman LP. Tyldesley’s Oral Medicine, 5th edn. Oxford: Oxford University Press,
2003. )
Background 1.3
Aphthous ulcers are painful oral
mucosal inflammatory ulcerative
conditions and frequently impact on
daily life especially activities such as
eating, swallowing and speaking.
(Tabolli S, Bergamo F, Alessandroni L, Di Pietro C, Sampogna F, Abeni D.
Quality of life and psychological problems of patients with oral mucosal
disease in dermatological practice. Dermatology (Basel, Switzerland).
2009;218(4):314-320.; Miller MF, Ship II. A retrospective study of the
prevalence and incidence of recurrent aphthous ulcers in a professional
population,1958-1971. Oral Surgery, Oral Medicine, Oral Pathology, Oral
Radiology, and Endodontology. 1977;43(4):532-7. )
Background 1.4
The symptoms of aphthous ulcers
can present in three main forms:
1. minor aphthous ulcers
2. major aphthous ulcers
3. herpetiform ulcers
Background 1.5
Minor aphthous ulcers the most
common form which appear as
small (less than 10 mm in
diameter), round, clearly defined,
painful ulcers. Healing occurs in
10 to 14 days without scarring.
EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children-a review.
International Journal Of Paediatric Dentistry 1992;2:1-10. )
Background 1.6
Major aphthous ulcers lesions
are larger (greater than 1 cm in
diameter). Healing of this form
of ulcer may take 20 to 30 days
or longer than minor aphthous
ulcers, and frequently results in
(Wray D, Ferguson MM, Mason DK, Hutcheon AW, Dagg JH.
Recurrent aphthae: treatment with vitamin B12, folic acid, and iron. British Medical Journal.
1975;2:490–3. )
Background 1.7
The least common variety of RAS
are herpetiform ulcers, which
present with multiple small and
painful ulcers, together with
clusters of pinpoint lesions which
often occur in multiples from 1 to
100, each being 2–3 mm. The ulcers
tend to fuse, producing large
irregular ulcers.
(Lehner T Progress report: oral ulceration and
Behgets syndrome. Gut. 1977;18:491-511.; Scully C, Porter S. Recurrent aphthous stomatitis:
urrent concepts of aetiology, pathogenesis and management. Journal of Oral Pathology &
Medicine. 1989;18:21-27.; Porter SR, Scully C. Aphthous stomatitis-an overview of
aetiopathogenesis and management. Clinical and Experimental Dermatology. 1992;16:235-243.)
Background 1.8
The cause of aphthous ulcers remains
unknown. Studies have found that
RAS patients who present to
physicians for treatment for
deficiencies of iron, folate, and
vitamin B12, record a 71%
improvement in aphthous ulcer
following replacement therapy for
these deficiencies.
(Olsen A, Feinberg I, Silverman S, Abrams D, Greenspan JS.
Serum vitamin B12 folate, and iron levels in recurrent oral ulceration. Oral Surgery, Oral Medicine, Oral Pathology, Oral
Radiology, and Endodontology.. 1982;54:517-520.; Piskin S, Sayan C, Durukan N, Senol M. Serum iron, ferritin, folic
acid, and vitamin B12 levels in recurrent aphthous stomatitis. Journal of the European Academy of Dermatology and
Venereology. 2002;16:66-7.)
Background 1.9
Several vitamin B12 (cobalamin)
treatments for RAS have addressed
the goals of decreasing pain, healing
time, number and size of the ulcer,
and to increase the number and
length of disease-free periods.
Vitamin B12 may play an important
role for aphthous ulcers. (Brachmann F. treatment of
chronically recurrent aphthae with vitamin B12. Zohnarztl welt. 1954;9:58-59.;
Dholakia KR, Dharmarajan TS, Yadav D, Oiseth S, Norkus EP, Pitchumoni CS. Vitamin
B12 deficiency and gastric histopathology in older patients. World Journal of
Gastroenterology. 2005;11:7078-83.; Dali-Youcef N, Andrès E. An update on cobalamin
deficiency in adults. Oxford Journals Medicine: Monthly Journal of the Association of
Physicians. 2009;102(1):17-28. )
Step 1. Systematic review
A Systematic Review for the vitamin
B12 in treating AS: randomized
controlled trials (RCT) of vitamin B12
treatment compared to placebo on adult
patients with recurrent AS, reported in
either the English or Chinese languages.
Search strategy
The Cochrane Central Register Controlled Trials
(CENTRAL), Database of Abstracts of Reviews of
Effectiveness, CINAHL, PubMed, ScienceDirect,
EBSCOhost and Chinese Electronic Periodicals
Service (CEPS) were searched from their inception
1970-date to April 2010, as well as reference lists
from relevant trials.
Search term and keywords included:
Vitamin B12,
Recurrent Aphthous Stomatitis
Mouth sore
Canker sore
Oral ulcer
Assessment of Methodological
Papers selected for retrieval were assessed
by two independent reviewers for
methodological validity prior to inclusion in
the review using a standardised critical
appraisal instrument from Joanna Briggs
Institute Meta-Analysis of Statistics
Assessment and Review Instrument (JBIMAStARI). Any disagreements that arose
between the reviewers were resolved
through discussion, or with a third reviewer
Data Extraction
Data was extracted from papers included in
the review using a standardised data
extraction tool from JBI-MAStARI. Data
extracted from included studies were
specific details about the interventions,
populations, study methods, patient
numbers in the treatment group, patient
numbers in the placebo group and
outcomes of significance to the review
question and specific objectives.
Data Synthesis
RCT reports were assessed for study details such as
the types of participants, methods, outcomes
measured, timing of the intervention and data
collection. The Cochrane Collaboration Review
Manager software was used for statistical pooling of
the data in meta-analysis (this was a deviation from
the protocol in which it was specified that JBIMAStARI would be used). Odds ratio (OR) for
categorical data and their 95% confidence interval
(CI) were calculated for analysis. Heterogeneity of
data was assessed using the standard Chi-square test.
Results of the review
These three RCTs used vitamin B12 improving
RAS as an outcome measure of the subject
perception of benefit, i.e. personal report to
their study clinics the individual feeling of
improvement, and homogeneity hypothesis was
not rejected (Chi2=1.17, p=0.56 and I2=0%).
This meta-analysis showed significant
improvement of RAS in intervention group
compared with control group (OR 0.16; 95%
CI (0.07, 0.37); p<0.0001).
Treatments for Vitamin B12 treating
Study or Subgroup
Vitamin B12
Odds Ratio
Odds Ratio
Events Total Events Total Weight M-H, Fixed, 95% CI
Bugress and Haley 2008
26 31.9%
0.25 [0.07, 0.87]
Volkov et al. 2009
27 43.6%
0.16 [0.05, 0.55]
Zhong, Mao and Li 2010
20 24.4%
0.04 [0.00, 0.83]
73 100.0%
0.16 [0.07, 0.37]
Total (95% CI)
Total events
Heterogeneity: Chi² = 1.17, df = 2 (P = 0.56); I² = 0%
Test for overall effect: Z = 4.37 (P < 0.0001)
M-H, Fixed, 95% CI
0.01 0.1
10 100
Favours experimental Favours control
Results of the review
Both studies in Burgess and Haley and in
Zhong, Mao and Li recorded their patient’s
pain relief.
This meta-analysis showed significant
improvement in pain relief among patients
with RAS in intervention group (OR 0.14;
95% CI (0.04, 0.47); p=0.001), and the
homogeneity hypothesis was not be rejected
Pain relief
Study or Subgroup
Vitamin B12
Odds Ratio
Odds Ratio
Events Total Events Total Weight M-H, Fixed, 95% CI
Bugress and Haley 2008
7 22.1%
0.25 [0.03, 2.24]
Zhong, Mao and Li 2010
5 20
20 77.9%
0.11 [0.03, 0.46]
27 100.0%
0.14 [0.04, 0.47]
Total (95% CI)
Total events
Heterogeneity: Chi² = 0.37, df = 1 (P = 0.54); I² = 0%
Test for overall effect: Z = 3.21 (P = 0.001)
M-H, Fixed, 95% CI
0.01 0.1
10 100
Favours experimental Favours control
Discussion 1.1
From systematic review, research end
results of Burgess and Haley 2008 and
Zhong, Mao and Li 2010 - Vitamin B12
treating AS assessed by the subject
perception of benefit, i.e. personal report
on feeling of improvement to study
Both studies in Burgess and Haley (2008)
and in Zhong, Mao and Li (Zhong et al.,
2010)64 recorded their patients’ pain
Discussion 1.2
However, the systematic review were insufficient data
to determine which dose of vitamin B12 and which
formulation under schedule time frame by minutes or
by days would be most beneficial for individuals in AS
situations or with specific baseline vitamin B12 levels.
In summary, on the basis of our analysis, a focus on
vitamin B12 treatment may be beneficial for patients
with AS. Although the meta-analysis was significant,
we must interpret the results carefully because of the
small size and the fact that the studies were so
different with respect to B12 dosage, mode of delivery,
and length of the treatment.
Implications for research 1.1
Sufficient large number of patients, RCTs in AS field
can consolidate evidence of effectiveness.
Quality observational studies are needed reflecting
actual treatment conditions.
Further research into benefits dose and method of
offering orally taken vitamin B12 with medications
should be conducted.
Inclusion of intention to treat AS should recorded age,
gender, diagnosis oral ulcer, diagnostic criteria,
severity, co-morbidities, and previous treatments,
treated as covariates in analyses, introducing the
potential for accurate results
Conclusion 1.1
The results of this study supported that the utilization of a
clinical nursing practice guideline for oral care could
reduce pain and duration of oral ulcer days of oral health
status. However, the study as designed was unable to
effect a reduction in recurrent oral ulcer rate. Further
research should increase sample size and select more
participants who have been recurrent oral ulcer.
Further clinical trials are required to provide a more
robust evidence base on this topic. Further research into
the prescription, administration and effectiveness should
focus on the following for sufficient large number of
patients, RCTs in AS field can consolidate evidence of
Using the Nursing Clinical
Guideline in Treating Aphthous
Stomatitis 2.1
We invited five experts who used focused
interviews an oral ulcer clinical nursing
practice guideline in treating AS. We discussed
and obtained information from individuals and
interactions among individuals in a small
group setting. All instruments were reviewed
for content validity and appropriateness of
language by the five experts, including a
physician specialized in oral care, a dentist,
two nurses lecturer specialized in oral hygiene
and two nurses in respiratory care of critically
ill patients.
Through randomization, six patients were
assigned to the experimental group and seven
patients were assigned to the control group.
Experimental group: The average age was 41.9
years and range 34~54 years. The duration of
intubation before the experiment of all
participants was less than seven days. Control
group: The average age was 53.43 years and
range 39~71 years.
The comparison between the control and
experimental groups in the three main
study measurements for treatment
effectiveness. The average duration of
oral ulcer episode (number of days):
experimental group during mean±sd
3.83±0.65 days and control groups
during 6.29±2.11 days of treatment.
The subjective level of pain (according
to the pain scale self-report):
experimental group reported 1.17±0.17
days and control groups reported
1.57±0.20 of treatment.
From the step 2 findings, the mean
scores for average duration of oral ulcer
episode (number of days) of oral ulcer
and reduce pain after treating a clinical
nursing practice guideline with vitamine
B12 of in the experimental group were
lower than those in the control group.

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