Kyrrolos Hanna - single EBP case study

Kyrrolos Hanna, Latrobe university of Bendigo, 2015

Evidence Based Practice

Contents

Abstract………………………………………………………………………………………………3

Introduction………………………………………………………………………………………4-6

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31st/05th/2015


Materials and methods……………………………………………………………………………6-7

Results………………………………………………………………………………………….8-10

Discussion…………………………………………………………………………………….11-12

Conclusion…………………………………………………………………………………….12

References…………………………………………………………………………………….12-13

Appendix………………………………………………………………………………………13-18

The effectiveness of Chlorhexidine in combination with

Hydrogen peroxide in treating Necrotizing Ulcerative

Gingivitis: a case study

Abstract

Aims: This before and after study aimed to assess and compare the relative clinical success of Chlorhexidine in

combination with hydrogen peroxide in effectively treating the signs and symptoms of Necrotizing ulcerative

gingivitis at 9 day intervals over a one month period.

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Methods: a Patient presenting with Necrotizing Ulcerative Gingivitis (n=1) was subject to an antimicrobial

regime consisting of 10ml of chlorhexidine gluconate (2%) and 10ml of hydrogen peroxide (1.5%), twice daily, in

9 day cycles, over the length of 1 month. This was evaluated by comparing intra oral photographs and pain

scales taken at the first and last visit. Frequency was assessed with the use of a chart and compliance was

evaluated by comparing this chart with standardized measurements of weight. Pertinent literature was reviewed

to select articles according to previously defined inclusion criteria.

Results: chlorhexidine gluconate (2%) and hydrogen peroxide (1.5%) significantly reduced the clinical

characteristics of Necrotizing Ulcerative Gingivitis in the patient with regards to inflammation and associated

pain.

Conclusion: although the outcome of this study showed a positive reduction in the severity of the signs and

symptoms of Necrotizing Ulcerative Gingivitis, the clinical significance of chlorhexidine and hydrogen peroxide

is inconclusive. However it may have implications in the management of such periodontal conditions.

Academic databases: Expanded Academic ASAP, EBSCO - Dentistry & Oral Sciences Source, Whiley online

library, Science direct, Cochrane library, Elsevier Journals and PubMed

Key words: Necrotizing Ulcerative Gingivitis, chlorhexidine, hydrogen peroxide, treatment, signs, symptoms,

pain, mechanisms, effects, etc.

Abbreviations: NUG (Necrotizing Ulcerative Gingivitis), CHX (chlorhexidine), H2O2 (hydrogen Peroxide).

Periodontal disease is a term used to describe

inflammation of the periodontal tissues and can

present in many forms (1). Studies show that it is

mostly caused by the accumulation of bacterial

plaque and poor oral hygiene where other factors

such as environmental, genetic and systemic

factors can contribute to periodontal disease

pathogenesis (2-4).

Necrotizing Ulcerative Gingivitis

The 5th classification of periodontal disease is NUG

which is different from other periodontal diseases in

that it presents with necrosis of the gingival tissues

(2, 5). This is a rare disease and has been shown

that its prevalence is higher in patients with poor

oral hygiene (2, 3, 5, 6). The cause of NUG is

similar to other periodontal diseases in that it is

mainly cause by bacterial plaque, although

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additional dynamics can contribute to its

pathogenesis such as stress, socioeconomic status,

smoking, and an altered host resistance (1, 2, 5).

Recent studies have found that there are specific

bacteria involved in NUG including fusiform

bacteria, Prevotella intermedia, and spirochetes (1,

5, 6).

The clinical signs of NUG can be generalized or

localized with rapid or sudden onset but is more

common in the anterior region of the mouth (2, 5). It

is characterized by a crater-like or “punched out”

interdental papilla, gingival bleeding and intense

pain where features including a fetid breath and a

grayish pseudomembranous film covering an

ulcerated papilla are common clinical appearances

(2, 5, 6). This condition can be accompanied by

secondary conditions such as lymphadenopathy,

fever and malaise which reflects a systemic aspect

to the incidence of NUG (2, 5). It is important to

note that severity can vary from case to case and

diagnosis of NUG should be based on specific

clinical examinations and investigations (see

Appendix 1 table 6) (2, 5). There can also be

differential diagnosis of NUG (see Appendix 2

table 7) (2, 5). The current literature states that the

reduction of oral bacteria, pain management and

providing the patient with specific oral hygiene

instructions are essential in achieving optimum

treatment outcomes (1, 2, 5). Professional removal

of calculus produces a rapid response and is aimed

primarily at reducing etiological factors to reduce or

eliminate inflammation, thereby promoting

periodontal healing (1, 2, 5).

It has been well established that mechanical plaque

removal in adjunction with antimicrobial mouthwash

is effective in inhibiting or reducing supra gingival

plaque formation, especially when mechanical oral

hygiene is difficult or impossible (1, 3, 7-10).

As suggested in the literature, chemotherapeutic

agents can be utilized in not only achieving and

maintaining optimum periodontal health but in

treating NUG(2). This consists of the bactericidal

and bacteriostatic properties of CHX and the

oxygenating effects of H2O2 (3, 9).

Chlorhexidine Gluconate

CHX is classified as a cationic antiseptic and is

found in mouthwash, gels, sprays, varnish and

toothpastes (3, 4, 11-13). This product has a wide

antimicrobial spectrum which effects gram positive

and negative bacteria, resulting in inhibition of

plaque formation (7, 9, 11, 14). It also comes in

varying concentrations where levels of 0.12% and

0.2% have been effective in significantly reducing

plaque and resolving gingivitis (3, 7-11, 14-16). The

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Table 1 Treatment of NUG (1, 2, 5, 6)

Control painPrescribe antibiotics if patient is immunocompromisedAmoxicillin, 250 mg 3 x daily for 7 days and/or Metronidazole, 250 mg 3 x daily for 7 daysPerform debridement

Local anesthesia Use of the ultrasonic for irrigation properties

Provide patient with specific oral hygiene instructionsMeticulous plaque controlAntibacterial mouthwash: chlorhexidine 0.12% in combination with hydrogen peroxide 1.5% twice dailySmoking cessationPatient counsellingFollow up with a comprehensive periodontal evaluation


recommended dosage of CHX is 10 ml of a 0.2%

solution, twice daily and has been shown to reduce

plaque by approximately 60% and reduce the

severity of gingivitis by 50–80% (3, 5, 7, 9, 10, 12,

14).

CHX acts on the bacterial cell wall by changing the

osmotic equilibrium in the cells membrane (9, 11).

This inevitably leads to cell lysis by precipitation of

bacterial contents (9, 11). The advantages of CHX

are essentially in its substantive abundance in the

mouth due to its binding effect on the hard and soft

tissues, allowing it to accumulate over a long period

after application (3, 9, 11, 14, 17). Studies show

that its effectiveness has been proven many times

over and this is why CHX is widely known as the

gold standard in plaque control (3, 4, 9, 11, 13, 14,

17). Disadvantages to the use of CHX is not only in

its bitter and unpleasant taste, but that repeated use

often produces stains and taste disturbances (4, 9-

11, 13, 16). It is also for this reason that the use of

CHX should be limited to no more than 2 weeks at a

time to reduce the accompanying side effects (9,

10, 13).

Hydrogen Peroxide

H2O2 is classified as an oxygenating, being known

for its use in the management of NUG (2, 4, 9-11).

Studies have demonstrated the efficacy of 1.5%

H2O2 in reducing plaque in the way that it

introduces oxygen to an anaerobic environment and

consequently disrupts the function of anaerobic

bacteria such as those found in the case of NUG (4,

9, 10). In addition, several studies have indicate that

the use of H2O2 can be helpful in controlling dental

stains associated with the use of CHX (4, 10, 11).

This occurs due to oxidation and reduction

reactions incorporated in the mechanisms of H2O2

which release by products that break the alkene

double bonds responsible for tooth discoloration(4).

This essential reduces plaque scores and prevents

stains, thus facilitating the effects of CHX and

assisting in the treatment of NUG(4).

Furthermore, a combination of CHX and H2O2, as

an adjunct to routine mechanical tooth cleansing

can be perceived as a rational implementation in

reducing the clinical signs and symptoms of

necrotizing periodontal diseases(9). This

combination enhances the efficacy of CHX in

reducing plaque formation and therefore

compliments the treatment of NUG(9).

Materials and method

Case description

A 19 year old female studying beauty therapy at

Bendigo TAFE presents to the student clinic for

routine examination. The patient reports that she

smokes 10 cigarettes a day and is concerned about

swollen and bleeding gums with accompanied pain.

Clinical examination shows generalized severe

inflammation of the gingiva, punched out papilla and

a greyish film along the cervical margins which is

descriptive of Type 5 A Necrotizing Ulcerative

Gingivitis.

Intervention

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The patient was given instructions to rinse with a

capful (10ml) of Colgate Savacol (alcohol free) for 2

minutes, 30 minutes after brushing and half a capful

(10ml) of Colgate Peroxyl for 1 minute after

Savacol. The patient was also instructed to limit

their use to twice a day for 9 day cycles due to

availability of appointment scheduling and evidence

based recommendations. Intra-oral photographs

were taken of the frontal view of the anterior teeth

for baseline characteristics and stored onto Digora

imaging software. A pain scale was provided to the

patient to illustrate sensitivity and intensity of

associated pain. The patient was requested to

supply a chart entailing the frequency of use for the

9 day intervals which was tallied upon final

evaluation.

Assessment

The effectiveness of the use of CHX and H2O2 was

evaluated by assessing visual characteristics and

recording pain expressed by the patient in the form

of a second pain scale. Intra oral photographs were

taken for a second time and compared with the

initial intra oral photographs. Observation of

characteristics such as inflammation, punched out

papilla and greyish film along the cervical margin

were key criteria in the comparison of the before

and after photos.

Fig 1 Colgate Savacol, alcohol free and Colgate Peroxyl utilized in the combination of Chlorhexidine and Hydrogen peroxide

Patient compliance

Validity of the patient’s compliance to this regime

was tested by gaining set values of weight and

using simple conversions to solve the rate of

frequency. The standardized weights for both

Savacol and Peroxyl that needed to be solved

included the original weight of the bottle (where vs is

360g and vp is 295g), the weight of the bottle alone

(where bs is 38g and bp is 36g), the weight of the

cap alone (where cs is 11g and cp is 6g) and the

weight of 10ml of solution (where ws is 11g and wp

is 11g).

Note: Lower case scripts illustrate the bottle in

question, (i.e.) ‘s’ for Savacol and ‘p’ for Peroxyl.

The bottles were then weighed at the 9th and 27th

day in the regime and deducted from the original

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standard weights to establish how much solution

was actually removed from the bottle. The

difference was then divided by the suggested

volumes of 10ml to figure out how many times this

specific dosage was taken. The results were then

cross referenced with the chart provided by the

patient in order to investigate credibility of the chart

(see table 5).

The following formulations were developed in order

to calculate the exact amount of Savacol and

Peroxyl used during the 1st and 2nd cycles.

f s=(vs−bs−cs )−(xs−bs−cs)

w s

f p=(v p−bp−c p )−(x p−bp−c p)

wp

f❑=number of×used

v❑=origionalweight of bottle

x❑=current weight of bottle

c❑=weight of cap alone

b=weight of bottle alone

w=weight of 10mlof solution

Results

The results showed a significant

reduction in the clinical

characteristics of NUG. The

contrast between the Intra oral

photographs taken at the first visit

compared to the one taken at the

last visit showed a noteworthy

improvement with regards to the

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Table 2 Clinical comparison of intra oral photographs before and after implementation of

CHX H2O2

Before After

Fig 2 Intra oral photograph depicting

the frontal view of the Anterior teeth

taken at the first visit

Fig 3 Intra oral photograph depicting the

frontal view of the anterior teeth, taken at

the final visit

Clinical characteristics

Inflamed gingivae Reduction in inflammation

Red gingivae Pink gingivae

Cratered papilla Firm papilla

Grayish film Absence of grayish film


inflammation of the gingivae, color of the gingivae, physical appearance of the papilla and presence of a grayish

film along the cervical margin.

In addition, the associated pain expressed by the patient at the initial examination compared with the pain

expressed at the final visit was substantially reduced.

As suggested by the chart supplied, the patient reported that there was a steady intake of Savacol and Peroxyl

in the first cycle whereas there was two evening sessions that were not recorded in the second cycle.

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Table 3 Comparison of pain scale supplied at the initial examination to pain scale supplied at the final appointmentBefore After

Fig 4 Pain pre-scale reflecting the patients perception of the

associated pain as Intense, dreadful, horrible pain

Fig 5 Pain post-scale reflecting how the patient no longer feels the so

called associated pain

Statistical tests

According to table 6 the frequency

reported by the patient in their chart did

not correlate with the results of the

volumes measured in the first cycle but

was more accurate at the following

cycle. The readings obtained show that

by the 9th day reported usage was <

the exact usage and

that by the 27th day reported usage

was more or less the same.

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Fig 6Fig 7 Structural formulation of Chlorhexidine Gluconate

Table 4 A chart demonstrating the frequency of intake of CHX and H2O2 as reported by the patient

AM PMCycle 1 Savacol Peroxyl Savacol Peroxyl

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Cycle 2

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Table 5 Comparison of reported frequency to exact frequency and specific formulations / calculations conducted

Evaluation

Mouth wash

Reported frequency

Calculations Measured use

Exact frequency

Validity Amount of times missed

Cycle 1

9 days

Savacol 18

f s=(360−38−11 )−(x s−38−11)

11

xs=154 g f s=14The Reported amount of usage did not match the measured amount of usage

4

Peroxyl 18

f p=(295−36−6 )−(x p−36−6)

11

x p=110 g f p=10The reported amount of usage did not match the measured amount of usage

8

Cycle 2

27 days

Savacol 16

f s=(360−38−11 )−(x s−38−11)

11

xs=176 g f s=16The reported amount of usage did match the measured amount of usage

None

Peroxyl 16

f p=(295−36−6 )−(x p−36−6)

11

x p=165 g f p=15The reported amount of usage slightly varied from the measured amount of usage

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Discussion

Qualitative data analysis was interpreted by

comparing the results observed with the use of the

pain scale and intraoral photographs. Validity and

reliability of the implementation of these products

was conducted through analysis of charts and

volumetric measurements. The results gathered

supported the evidence that the combination of

CHX and H2O2 is effective in treating NUG (2, 4, 5,

10, 14, 18, 19). It was clear that there had been

improvement in regards to visual signs associated

with NUG with regards to inflammation and redness

of the gingivae. Similarly the results showed a

distinctive reduction in the severity of pain

expressed by the patient and this in turn endorses

the current views of studies in this area (2).

Limitations

Upon further assessment of the patient’s medical

history it was revealed that the patient had

undertaken a course of antibiotic therapy

(Metronidazole) during the period of

implementation. This has been identified as an

extraneous variable that could have affected the

results of this intervention and essentially renders

the effect of the chemical aids as partially

inaccurate (1, 2, 5). Although the current literature

suggests that antibiotic therapy is recommended in

the case of systemic toxicity (1, 2, 5), this additional

variable could have taken part in the reduction of

the clinical signs and symptoms of NUG. Hence the

true success of these aids is questionable due to

the potential interference of the course of antibiotic

therapy.

With regards to credibility of the reported use, it was

observed that there was a noteworthy difference

between the first and second cycle. The statistical

tests in place were developed in order to ensure

patient compliance and ensure adherence to the

instructions provided. However this only had a

direct effect after the first test was conducted after

the first cycle. It can be established that this

assessment provided the patient with the directive

for stringent adherence to the regime and therefore

the results may not decipher if these chemical aids

were effective with regards to user-friendliness

aspects.

In light of the large discrepancy between the

reported usage and measured usage in the first

cycle, the results up to that point were not reflective

of one another and therefore a detailed picture of

intake cannot be made. With regards to the two

sessions missed in the second cycle, it could not be

established as to whether the times were forgotten

or that the patient simply did not record them for

those intervals.

In addition, the results of the measured use of

Peroxyl was 1 capful less than the reported use of

Peroxyl in the second cycle. In retrospect,

consideration of spillage must be taken into account

when equating these two measurements. However,

in view of the remarkable effect of this combination

this variable has been deemed insignificant in

tarnishing the validity of the recognized outcomes.

It is important to note that the use of the pain scale

may limit the ability to assess the true reduction in

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pain intensity due to its subjective nature and so

marginal error is expected. This however was

slightly controlled by using the same operator and

surgery to produce a similar environment.

Another limitation is the fact that patient treatment

was undertaken during the implementation of these

aids. The variable of debridement in this given time

could have played a role in the reduction of the

signs and symptoms of NUG and therefore also

deems the results inaccurate.

Conclusion

The outcome of this study showed a positive

reduction in the severity of the signs and symptoms

of Necrotizing Ulcerative Gingivitis with the use of

chlorhexidine and hydrogen peroxide. However the

limitations of antibiotic therapy, spillage, periodontal

treatment and the subjective nature of the

expression of pain diminished conclusive evidence

for this intervention. Furthermore, a larger sample

size and an extended period of time would have

proved beneficial and produced a clear outcome on

the benefits of chlorhexidine and hydrogen peroxide

in the treatment of Necrotizing Ulcerative Gingivitis.

References1. Periodontology AAo. Treatment of Plaque-induced Gingivitis, Chronic Periodontitis, and Other Clinical Conditions. Pediatric Dentistry. 2010 10//2010 Reference Manual;32(6):290-9. PubMed PMID: 54737456.2. Alpagot T. Necrotizing Ulcerative Gingivitis and Periodontitis, and Chronic Periodontitis. People's Medical Publishing House USA Ltd (PMPH); 2003. p. 52-3.3. Cristian M, Luca R. UTILIZATION OF CHLORHEXIDINE IN PROPHILACTIC TECHNIQUES OF

PROFESSIONAL HYGIENIZATION. International Journal of Medical Dentistry. 2014 07//Jul-Sep2014;4(3):171-6. PubMed PMID: 99582769.4. Jhingta P, Bhardwaj A, Sharma D, Kumar N, Bhardwaj VK, Vaid S. Effect of hydrogen peroxide mouthwash as an adjunct to chlorhexidine on stains and plaque. Journal of Indian Society of Periodontology. 2013 07//Jul-Aug2013;17(4):449-53. PubMed PMID: 91265246.5. Atout RN, Todescan S. Managing Patients with Necrotizing Ulcerative Gingivitis. Journal of the Canadian Dental Association. 2013 03//;79(2):1-4. PubMed PMID: 88167399.6. Falkler WA, Jr, Martin SA, Vincent JW, Tall AA, Nauman RK, et al. A clinical, demographic and microbiologic study of ANUG patients in an urban dental school. Journal of Clinical Periodontology. 1987 07//;14(6):307-14. PubMed PMID: 13467446.7. Charles CH, Mostler KM, Bartels LL, Mankodi SM. Comparative antiplaque and antigingivitis effectiveness of a chlorhexidine and an essential oil mouthrinse: 6-month clinical trial. Journal of Clinical Periodontology. 2004;31(10):878-84.8. Garcia RI. Mouthrinses and Dentifrices are Effective Antigingivitis and Antiplaque Agents. Journal of Evidence Based Dental Practice. 2008 3//;8(1):13-4.9. Eley B. Antibacterial agents in the control of supragingival plaque -- a review. British Dental Journal. 1999 03/27/;186(6):286. PubMed PMID: 9354177.10. Gusberti FA, Sampathkumar P, Siegrist BE, Lang NP. Microbiological and clinical effects of chlorhexidine digluconate and hydrogen peroxide mouthrinses on developing plaque and gingivitis. Journal of Clinical Periodontology. 1988 01//;15(1):60-7. PubMed PMID: 13476974.11. Paraskevas S. Randomized controlled clinical trials on agents used for chemical plaque control. International Journal of Dental Hygiene. 2005;3(4):162-78.12. Ribeiro LGM, Hashizume LN, Maltz M. The effect of different formulations of chlorhexidine in reducing levels of mutans streptococci in the oral cavity: A systematic review of the literature. Journal of Dentistry. 2007 05//;35(5):359-70. PubMed PMID: 24711341.13. Wu CD, Savitt ED. Evaluation of the safety and efficacy of over-the-counter oral hygiene products for the reduction and control of plaque and gingivitis. Periodontology 2000. 2002;28(1):91-105.

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14. Van Strydonck DAC, Slot DE, Van der Velden U, Van der Weijden F. Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. Journal of Clinical Periodontology. 2012;39(11):1042-55.15. Gunsolley JC. A meta-analysis of six-month studies of antiplaque and antigingivitis agents. (cover story). Journal of the American Dental Association (JADA). 2006 12//;137(12):1649-57. PubMed PMID: 23501375.16. chlorhexidine Csoad, mouth rinses on the level

of dental staining and gingival indices{Najafi N, Mohammad Hassan, Taheri M, Mokhtari MR, Forouzanfar A, Farazi F, et al. Comparative study of 0.2% and 0.12% digluconate chlorhexidine mouth rinses on the level of dental staining and gingival indices. Dental

Research Journal. 2012 05//;9(3):305-8. PubMed PMID: 92014451.17. Tomás I, Cousido MC, García-Caballero L, Rubido S, Limeres J, Diz P. Substantivity of a single chlorhexidine mouthwash on salivary flora: Influence of intrinsic and extrinsic factors. Journal of Dentistry. 2010 07//;38(7):541-6. PubMed PMID: 51153652.18. Miyasaki KT, Genco RJ, Wilson ME. Antimicrobial Properties of Hydrogen Peroxide and Sodium Bicarbonate Individually and in Combination Against Selected Oral, Gram-negative, Facultative Bacteria. Journal of Dental Research. 1986 09//;65(9):1142-8. PubMed PMID: 36543720.19. Gunsolley JC. Clinical efficacy of antimicrobial mouthrinses. Journal of Dentistry. 2010 06/02/Jun2010 Supplement 1;38:S6-S10. PubMed PMID: 52243869.

Appendix

The following tools were utilized within the implementation and investigation outlined in the case study.

This consisted of:

Foundation knowledge in the form of tables

Additional diagnostic evidence in the form of intra oral photographs

Patient instructions in the form of pamphlets, charts and scales.

By incorporating these reusable tools into the implementation process, a rationalized approach to

patient instructions and analysis of the outcomes of this case were established.

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Appendix 1 (table 6) Investigations in assessing NUG (2, 5)

Medical historyNutrition and health habitsConsultation with a general practitioner if immunosuppressive disease is suspectedDental historyPainExtraoral examinationLymphadenopathy of the head and neckIntraoral examinationClinical features of NUG

Appendix 2 (table 7) Differential diagnosis of NUG (1, 2, 5)

Primary Herpetic GingivostomatitisDesquamative GingivitisAgranulocytosisCyclic NeutropeniaLeukemiaAscorbic Acid DeficiencyGingivitisAphthos Stomatitis


Fig 8 & 9 Colgate brochure implemented in the provision of CHX and H2O2

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Fig 10 Ethical clearance at the time of the initial intra oral photography

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Fig 11 Ethical clearance at the time of the final intra oral photography

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Patient pain scale Please discribe the pain associated with your condition based on the scale provided below. This

description is to compare the symptoms of your condition before the impementation of a combination

of chemical aids.

Please discribe the pain associated with your condition based on the scale provided below. This

description is to compare the symptoms of your condition after the impementation of a combination of

chemical aids.

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http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://homepage.cs.latrobe.edu.au/ypchen/APBC2012/&ei=4XVRVfXRHobs8gXB4YOQBQ&bvm=bv.92885102,d.dGc&psig=AFQjCNGpU3P6k9ldmCAeOkdISgCPA33X7A&ust=1431488341695915


Patient Hygiene chartPlease fill out this chart every time the chemical aids Savacol and Peroxyl are used.

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AM PMCycle 1 Savacol Peroxyl Savacol Peroxyl

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Cycle 2

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://homepage.cs.latrobe.edu.au/ypchen/APBC2012/&ei=4XVRVfXRHobs8gXB4YOQBQ&bvm=bv.92885102,d.dGc&psig=AFQjCNGpU3P6k9ldmCAeOkdISgCPA33X7A&ust=1431488341695915

Kyrrolos Hanna - single EBP case study

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