public health, prevention, dentistry

1. RANDOMIZED CLINICAL TRIAL OF A TOPICAL
BOTANICAL PATCH FOR THE ADJUNCTIVE
MANAGEMENT OF PERIODONTITIS
Rebecca Wilder/William Levine/David W
Paquette
Oral Health Prev Dent 2022; 20: 253-262
Doi: 10.3290/j.ohpd.b3147141
By
Dr. Souma Shankar Mukherjee

2. TABLE OF CONTENTS
PROLOGUE
01
ABSTRACT
02
METHODOLOGY
03
DISCUSSION
04
LIMITATIONS
05
CONCLUSIONS
06

3. PROLOGUE
01

4. INTRODUCTION
Periodontitis is a common
condition in human population
and is initiated by a dysbiosis of
the oral microbiome , leading to
inflammatory events and the
destruction of tooth supporting
tissues (alveolar bone,
periodontal ligament and
connective tissue) [Curtis 2000]

5. Host Modulation Therapy
Host is defined as the organism
from which the parasite derives
its nourishment
Modulation is defined as the alteration
of function or status of something in
response to a stimulus or an altered
chemical or physical environment
Williams and Golub et al
introduced the concept of host
modulation in dentistry.

6. Host Modulation Therapy
BASIC CONCEPT
Most of the destruction of
periodontium is due to pro-
inflammatory mediators of the host.
The main causes are:
MMP-Host derived destructive
enzyme
Cytokines and prostanoids-Causes
changes in osteoclast activity
Increase the protective or anti-
inflammatory mediators

7. Host Modulation Therapy
DRUGS USED
LOCALLY
SYSTEMICALLY

8. Host Modulation Therapy
SYSTEMIC
NSAIDS
BISPHOSPHONATES
SDD- Sub Antimicrobial Dose
Doxycycline
20mg dose of doxycycline used
as an adjunct for SRP-Periostat
Inhibition of MMP, Cytokines and
Osteoclast activity but not
antimicrobial.
Only Systemic HMT approved by
US FDA and accepted by ADA

9. Host Modulation Therapy
LOCAL
• NSAIDs
• Enamel Matrix Proteins
• Growth Factors
• Bone Morphogenic Proteins

10. Host Modulation Therapy
LDD

11. Host Modulation Therapy
LDD

12. Host Modulation Therapy
LDD

13. Host Modulation Therapy
LDD

14. Host Modulation Therapy
PERIO PATCH
• The patch is a Class I medical device consisting of two layers: the outer backing and the gel
layers.
• Both layers provide protection from irritation that can occur from eating and speaking.
• PerioPatch® (Izun Pharmaceuticals© Ltd., Jerusalem, Israel) is a topical hydrogel patch that
adheres and immediately conforms to the shape of the soft tissues.
• The physical barrier created by PerioPatch® absorbs wound exudates and protects the oral
mucosa from trauma and possible irritants that could aggravate the wound, thus, improving
patients’ comfort.
• This hydrogel patch is composed of an absorptive polymolecular matrix based on natural
plant extracts.

15. Host Modulation Therapy
PERIO PATCH
Centella asiatica, commonly known
as brahmi,is native to tropical
regions of Africa, Asia, Australia, and
islands in the western Pacific
Ocean.It is consumed as a
culinary vegetable and is used
in traditional medicine.
Echinacea purpurea, the eastern
purple coneflower is a North
America Species of flowering
plant in the family Asteraceae. It
is native to parts of eastern North
America
Sambucus nigra is a species
complex of flowering plants in
the family Adoxaceae native to
most of Europe.

16. Host Modulation Therapy
PERIO PATCH

17. Host Modulation Therapy
PERIO PATCH

18. Host Modulation Therapy
PERIO PATCH

19. Staistical Tests
ANOVA
• ANOVA tests three or more groups for mean differences of continuous
response variable
• One Way ANOVA compares levels (i.e. groups of a single factor)
• Two way ANOVA compares levels of two or more factors

20. Staistical Tests
ANOVA

21. Staistical Tests
ANOVA

22. Staistical Tests
ANCOVA
• C stands for co-variance
• Like ANOVA, ANCOVA has a single continuous response variable
• Unlike ANOVA, ANCOVA compares a response variable by both a factor
and a continuous independent variable.
• The continuous independent variable used in ANCOVA is known as
“covariate”

23. Staistical Tests
ANCOVA

24. ABSTRACT
02

25. ABSTRACT

26. METHODOLOGY
STUDY DESIGN
RCT (PARALLEL, SINGLE CENTRE, SINGLE
BLINDED)
SAMPLING TECHNIQUE CONVENIENCE SAMPLING
(HOSPITAL BASED STUDY)
STUDY SETTING UNC-CH ADAMS SCHOOL OF DENTISTRY
STUDY DURATION 3 MONTHS

27. METHODOLOGY
SAMPLE SIZE ESTIMATION
• Formula for normally
distributed means
• P value-0.05
• Power-80%
• Mean – 0.6mm PD
• SD-0.9
INCLUSION CRITERIA
• Dentate Individual (>=12)
• Medically healthy or stable
• Two sites >6mm
• BOP at baseline
EXCLUSION CRITERIA
• Anti-inflammatory drugs
• Antibiotics (within 3 months
of screening)
• Drugs affecting periodontal
status(phenytoin, calcium
agonists, cyclosporin)
• Allergies to botanical
products

28. METHODOLOGY
• Examiners trained on measuring outcomes prior to the study in order to
achieve > 90% inter and intra examiner agreement for primary study
outcome
• Periodontal probing measurements – UNC 15 probe – All teeth except third
molars – 6 sites.
• PD, CAL, BOP,PI and GI
• PD/Cal between 2 mm reading – rounded down and took the lower reading
Multiple pass probing measurements
• Two to four treatment sites with mean PD>=6mm and BOP at baseline.

29. METHODOLOGY
• Randomization was done by treating clinicians
• Evaluaters (calibrated) were blinded
• Botanical patch group instructed on patch application
• Not to brush or floss on the area and not to eat for 1 hour after placement.
• Reapplication on days 0 (6-h apart)
• Once per day on days 1-6
• Patient recalled at 1, 2 and 3 months

30. RESULT

31. RESULT

32. RESULT

33. RESULT

34. RESULT

35. DISCUSSION
Aims and Objectives Results Inference
• A study was conducted by
Williams et al in the year 2001
• Examine the efficacy of adjunct
(minocycline microspores).
Significantly improved PD at 1, 3, 6
and 9 months as compared to SRP
alone.
SIMILAR

36. DISCUSSION
Aims and Objectives Results Inference
• A study was conducted by
Jeffcoat et al in the year 2001
• Examine the efficacy of adjunct
(chlorhexidine chips).
Significantly improved PD at only 6
weeks and significant CAL gains at
3 and 6 months as compared to
SRP alone.
SIMILAR

37. CROSS REFRERENCE

38. LIMITATIONS
• Sample size (Generalizability)
• Short Trial Duration
• Stratification strategies during randomization
• Clustering of smokers in the control group

39. CONCLUSION
• Botanical patch device resulted in short term improvements when
used as an adjunct with SRP especially in non-smoking periodontitis
patients.

40. CRITICAL EVALUATION
SOURCE OF THE ARTICLE: ORAL HEALTH AND
PREVENTIVE DENTISTRY

41. ABOUT THE JOURNAL
Peer Reviewed
Publisher: Quintessence Publishing
Editor: Prof. Dr. med. dent. Dr. hc Anton Sculean MSc, Dr. Poul Erik
Petersen, Prof. Dr. Avijit Banerjee
Section Under Which Article Was Published: Original Article
Publication Frequency: Irregular

42. DOI:DOI: 10.3290/j.ohpd.b3147141
Submitted: 21/11/18
Accepted: 26/04/22
Year of publication: 2022
Volume : 20
Impact factor: 1.595

43. About the Authors
Author name and institutional attachment mentioned
Designation mentioned for the authors
Department mentioned
Correspondence address and mail access mentioned

44. Rebecca Wilder
• Associate Dean for Professional Development and faculty affairs, Adams
School of Dentistry, University of North Carolina
• 61 Publications
AREA OF INTEREST
• Devices to treat dentinal hypersensitivity, plaque
accumulation and inflammation.

45. William Levine
• Chief Scientific Officer, Izun Pharmaceuticals, Jerusalem, Israel.

46. David Paquette
• Associate dean of research, School of Dental Medicine, East Carolina
University, Greenville.
AREA OF INTEREST
• Risk factors of periodontitis (Smoking and diabetes)

47. CONSORT Guidelines
1. Title and abstract
(a) Identification as a randomised trial in the title Mentioned
(b) Structured summary of trial design, methods,
results, and conclusions
Mentioned

48. TITLE
● Short and Meaningful
● Reflects the aim of the study.
● Study design is mentioned.
● Study population is not mentioned.
● Study location is not mentioned.

49. ABSTRACT
● Structured and Informative
● Primary aim is mentioned
● Study population is not mentioned
● Study design is mentioned
● Methodology has been mentioned.
● Statistical tests are mentioned; p-value is
mentioned
● Conclusion is in line with the aims.
● Information given in the abstract matches with
the text.

50. INTRODUCTION
Introduction
2. Background
and Objectives
(a)Scientific background and explanation
of rationale
Mentioned
(b)Specific objectives or hypotheses Mentioned

51. ● Seminar approach
● It conveys the need for study
● Meaningful and comprehensive
● Aim is mentioned
● Citations are relevant

52. METHODOLOGY
Methods
3. Trial Design (a) Description of trial design (such as parallel,
factorial) including allocation ratio
Mentioned
(b) Important changes to methods after trial
commencement (such as eligibility criteria), with
reasons
No changes
were made
4. Participants (a) Eligibility criteria for participants Mentioned
(b) Settings and locations where the data were
collected
Mentioned

53. 5. Intervention The interventions for each group with sufficient details to
allow replication, including how and when they were
actually administered
Mentioned
6. Outcomes (a) Completely defined pre-specified primary and
secondary outcome measures, including how and when
they were assessed
Mentioned
(b) Any changes to trial outcomes after the trial
commenced, with reasons
No
changes
7. Sample size (a) How sample size was determined Mentioned
(b) When applicable, explanation of any interim analyses
and stopping guidelines
-

54. Randomization
8. Sequence
generation
(a) Method used to generate the random allocation
sequence
Not mentioned
(b) Type of randomisation; details of any restriction
(such as blocking and block size)
Not mentioned
9. Allocation
concealment
mechanism
Mechanism used to implement the random allocation
sequence (such as sequentially numbered
containers), describing any steps taken to conceal the
sequence until interventions were assigned
Not mentioned
10. Implement-
ation
Who generated the random allocation sequence, who
enrolled participants, and who assigned participants to
interventions
Partially
Mentioned

55. 11. Blinding (a) If done, who was blinded after assignment to
interventions (for example, participants, care
providers, those assessing outcomes) and how
Investigator at
baseline
(b) If relevant, description of the similarity of
interventions
-
12. Statistical
methods
(a) Statistical methods used to compare groups for
primary and secondary outcomes
ANOVA,
ANCOVA
(b) Methods for additional analyses, such as
subgroup analyses and adjusted analyses
Logistic
Regression

56. RESULTS
13. Participant
flow (a diagram is
strongly
recommended)
(a) For each group, the numbers of participants
who were randomly assigned, received intended
treatment, and were analysed for the primary
outcome
Flow diagram not
mentioned
(b) For each group, losses and exclusions after
randomisation, together with reasons
Mentioned

57. 14. Recruitment (a) Dates defining the periods of recruitment and
follow-up
Mentioned
(b) Why the trial ended or was stopped -
15. Baseline data A table showing baseline demographic and clinical
characteristics for each group
Mentioned
16. Numbers
analysed
For each group, number of participants (denominator)
included in each analysis and whether the analysis
was by original assigned groups
Mentioned

58. 17. Outcomes
and estimation
(a) For each primary and secondary outcome,
results for each group, and the estimated effect
size and its precision (such as 95% confidence
interval)
CI Not mentioned
(b) For binary outcomes, presentation of both
absolute and relative effect sizes is
recommended
-

59. 18. Ancillary
analysis
Results of any other analyses
performed, including subgroup
analyses and adjusted analyses,
distinguishing pre-specified from
exploratory
Smokers, Non-
smoker, >7mm
pocket depth
19. Harms All important harms or unintended
effects in each group
Mentioned

60. • Results are presented in a logical and comprehensive
manner.
• Presented in table and text form, and both the data
match
• Tables and figure are numbered and titled properly.
• Accompanied by footnotes.
• Results are based on the objectives of the study.

61. CONCLUSION
● Conclusion is mentioned
● It is in line with the aim of the study

62. Other information
● Acknowledgement- Mentioned
● Conflict of Interest- Not mentioned
23. Registration Registration number and name
of trial registry
Not mentioned
24. Protocol Where the full trial protocol can
be accessed, if available
Not mentioned
25. Funding Sources of funding and other
support (such as supply of
drugs), role of funders
Mentioned

63. references
● 26
● Vancouver style of referencing

64. CRITICAL REFLECTION
PRESENT
STUDY
GENERALIZABILITY
PUBLIC
HEALTH
SIGNIFICANCE
REPRODUCIBILITY

65. THANK YOU