系統文獻查證 398 (五) Effectiveness of Vitamin B12 on Recurrent Aphthous Stomatitis in long term care: a Systematic Review Centre conducting review The Taiwan Joanna Briggs Institute Collaborating Centre : A Collaborating Centre of the Joanna Briggs Institute, National Yang-Ming University, Taipei, Taiwan Primary reviewer/contact Hsin-Li Liu, RN, MSN. 1.2 Contact: [email protected]Reviewer panel: Ruo-ping Han, PhD. 1 Yueh-Juen Hwu, PhD. 1.2 Shu Chin Chiu, RN. 2.3 Kai-Yu Tseng, PhD. 1.2 Lee-Wen,Pai RN, MSN. 1.2 1. Central Taiwan University of Science and Technology. 2. A Collaborating Centre of the Joanna Briggs Institute, National Yang-Ming University, Taipei, Taiwan 3. Feng-Yuan Hospital Department of Health Background Recurrent Aphthous Stomatitis (RAS) also known as canker sores, is one of the most common oral mucosa inflammatory ulcerative diseases worldwide. RAS is also an idiopathic condition in most patients. 1 The Aphthous ulcer condition is characterized by localized, shallow, rounded, painful, small, clean borders, a peripheral erythematous halo, and a yellow or grayish, base. Aphthous ulcers usually occur in recurrent bouts at intervals of a few days to a few months. 1.2.3 Aphthous ulcers are painful sores that can occur anywhere inside the mouth, include 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 tonsillar areas. 4 It is one of the most painful oral mucosal
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系統文獻查證
398
(五) Effectiveness of Vitamin B12 on Recurrent Aphthous Stomatitis in long term care: a Systematic Review
Centre conducting review
The Taiwan Joanna Briggs Institute Collaborating Centre : A Collaborating Centre of the
Joanna Briggs Institute, National Yang-Ming University, Taipei, Taiwan
medications, and human immunodeficiency virus infection and environment. 1.2.Nutritional
deficiencies or hemotologic diseases have been documented in 20% of patients with RAS. 45.46 When Studies have found that patients to physicians for treatment for deficiencies of iron,
folate, and vitamin B12, record a 71% improvement in aphthous ulcer following replacement
therapy. 47.48 The lack of clarity regarding the aetiology of aphthous ulcers has resulted in
treatments that are largely empirical. A medline search, starting at the year 1951, found 578
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articles related to the treatment of RAS, including 110 clinical trials. Medical preparations
from Licorice herbs 49.50.51 Myrtus communis (myrtle) herbs 52 and multivitamins, 53 adhesive
pastes, 54 local antiseptics, 55 local and systemic antibiotics, 56 topical non-steroidal
anti-inflammatory drugs, 57 topical corticosteroids, 58 and even topical and systemic
immunomodulators, immunosuppressants, and corticosteroids 59.60.61 were among the
treatments given to patients with RAS.
Several Vitamin B12 (cobalamin) treatment for RAS have addressed this, the goals
being to decrease pain, healing time, number and size of the ulcer, and to increase disease-free
periods, vitamin B12may play an important role for Aphthous ulcers. A study by Brachmann
(1954) first suggested Vitamin B12 deficiency could be associated with Aphthous ulcers.
62 The most common etiology of Vitamin B12 deficiency is food-cobalamin malabsorption
resulting from gastric dysfunction. 63 Studies which examined the impact of age suggest a
high prevalence of subnormal cobalamin concentrations, 64 and in some reports, an inverse
relationship between age and serum cobalamin concentrations. 65.66 Burgan and colleagues, in
their study of 143 patients experiencing recurrent aphthous stomatitis, found that 26.6% of
aphthous subjects demonstrated B12 deficiency in contrast to 12.6% of the controls. 67 Piskin
et al. found 35 patients with RAS who have vitamin B12 levels were found to be significantly
lower than 26 healthy controls, while significant differences were not found for the other
assessed hematological factors. 48 Volkov et al. was used a randomized, double-blind,
placebo-controlled trial to confirmed the vitmin B12 in the RAS of treatment. Study suggests
that daily 1000mcg vitamin B12 under the tongue may be preventive for Aphthous ulcers after
5 and 6 months of use, 68 it was found that high levels of vitmin B12 seemed to reduce the
incidence of ulcers. 69
Burgress and Haley suggest that 500mcg Vitamin B12 30 discs with instructions to use
two initially and then one each succeeding day, placing into saliva via adherent discs adhered
to the buccal side of a tooth and disc dissolved over 20 to 40 minutes, it near an ulcer when
present. All were instructed to make careful observations of their ulcers and report their
observations at least once each week over a 30-day period. can result in the seven subjects
who received the active discs, all seven (100%) reported a benefit. Six out of seven reported
reduced duration of each ulcer, four out of seven reported less peak pain from each ulcer, and
four out of seven reported lower frequencies of ulcers. This initial data suggested that the
discs might reduce frequency of minor RAU and reduce duration and peak pain levels of
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ulcers. 67
Treatment with vitamin B12 by oral supplementation is safe, inexpensive and effective
for RAS. 36.37.38 Nonetheless, despite the results of the above studies, the potential effect of
Vitamin B12 on Aphthous ulcers is not well established. The purpose of this review was to
study whether the daily used Vitamin B12 via oral supplements may be an effective strategy
for reducing the number, duration, and pain of Aphthous ulcers.
The Cochrane Library, Joanna Briggs Institute (JBI) database and CINAHL databases have
been searched and no previous systematic reviews on this specifc topic were identified as
being published or underway.
REVIEW QUESTION(S)/OBJECTIVES
The review objective is to synthesize the best available evidence on the effectiveness of
daily orally taken vitamin B12 on the incidence, duration or severity of Recurrent Aphthous
Stomatitis RAS.
Inclusion criteria
Types of Studies
The review will consider any randomized controlled trials undertaken in in-patient and
out-patient settings. In the absence of RCTs, other research study designs, such as
non-randomized or quasi-randomized controlled trials and before-and-after studies, will be
considered for inclusion.
Types of Participants
Adults 18 + years old With Recurrent Aphthous Stomatitis RAS of either gender will be
considered eligible.
Types of Interventions
daily orally taken vitamin B12
Types of Outcome measures
The outcome measures will include:
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(1) Incidence of RAS expressed as the proportion of participants experiencing one or more
Aphthous ulcers or expressed as number and size of the ulcer during the study period
(2) Duration of RAS episodes expressed as the average number of days of RAS episodes.
(3) Severity of these RAS episodes
Search strategy
The search strategy is designed to identify all published and unpublished papers in
English language from 1970 to present. The search will proceed in three stages, as follows;
An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis
of the text words contained in the title and abstract, and of the index terms used to describe
article. A second search using all identified keywords and index terms will then be undertaken
across all included databases.
The databases to be search include:
Cochrane Central Register Controlled Trials (CENTRAL),
Joanna Briggs Institute Library of Systematic Reviews
Database of Abstracts of Reviews of Effectiveness.
CINAHL
PubMed
ScienceDirect
MEDNAR
Dissertation International
Conference Proceedings
The specific disease descriptor to be added to the search strategy for each database is
1.Recurrent Aphthous Stomatitis
2.Canker sore
3.Oral ulcer
4.Mouth sore
5.cobalamin
Search term and keywords included
1.Vitamin B12
2.Recurrent Aphthous Stomatitis
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3.Mouth sore
4.Aphthae
5.Canker sore
6. cobalamin
7. Vitamin B12 RCT
8. cobalamin RCT
9. Combine 1 or 2
10. Combine 3 or 4
11. Combine 5 or 6
12. Combine 2 or 7
13. Combine 2 or 8
14. Combine 7 and 8
15. Combine 2 or 3 or 7
16. Combine 2 or 3 or 8
Assessment of Methodological Quality
Papers selected for retrieval will be assessed by two independent reviewers for
methodological validity prior to inclusion in the review using two standardized critical
appraisal instruments from the JBI-MAStARI (Joanna Briggs Institute-Meta-Analysis of
Statistics Assessment and Review Instrument) (Appendix I) will be used. Any disagreements
that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Data Collection/Extraction
Data will be extracted from papers included in the review using standardized data
extraction tools from the JBI-MAStARI. (Appendix II) Data extracted from
experimental/observational studies will include specific details about the interventions,
populations, study methods and outcomes of significance to the review question and specific
objectives.
Data Synthesis
Quantitative papers will, where possible, be pooled using the JBIMAStARI. All results
will be subject to double data entry. Odds ratio (for categorical data) and weighted mean
differences (for continuous data) and their 95% confidence intervals will be calculated for
analysis. Heterogeneity will be assessed using the standard Chi-square. Where statistical
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pooling is not possible the findings will be presented in narrative form.
Potential Conflict(s) of Interest
No conflict of interest.
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References
1. Porter SR, Hegarty A, Kaliakatsou F, Hodgson TA, Scully C.Recurrent aphthous
stomatitis. Clin Dermatol 2000;18:569-78
2. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med