Evaluation of the efficacy of two potassium nitrate bioadhesive gels (5% and 10%) in the treatment of dentine hypersensitivity. A randomised clinical trial.

Abstract

A randomised clinical trial was designed to compare the immediate efficacy (48-96 h) of two treatments with bioadhesive gels with different concentrations of potassium nitrate (NK 5% versus NK 10%) on dentine hypersensitivity (DH). We evaluated DH by means of the use of the evaporative stimulus (ES), as the main outcome, using a placebo control group as reference.
Forty-five consecutive patients who, after stimulation with a blast of air, had at least one tooth with DH > or = 2 according to the verbal ratings scale (VRS) scale were selected. They were randomly treated with a bioadhesive gel with 5% NK, 10% NK or a placebo gel without NK. The DH was evaluated at baseline, days 2, 4, 7 and 14 by an examiner blind to the procedure. The response to the ES with a blast of air, to the tactile stimulation with a probe and the subjective evaluation of the patient measured on the VRS scale were recorded. Statistical analysis was made using the Kruskal-Wallis test.
A greater reduction of DH after ES was observed after 48 h of treatment in the NK10% group (35.8%) compared to the NK5% group and placebo group (11.8% and 13.4%, respectively). This difference increased significantly at 96 h (p=0.003). No significant differences were observed for the other variables. These preliminary results may support the usefulness of an NK 10% gel to reduce the DH after stimulation with a blast of air during the first 4 days of its appearance.

Full text

Page 1

Evaluation of theefficacy of two
potassium nitrate bioadhesive
gels (5% and 10%) inthe
treatment of dentine
hypersensitivity. Arandomised
clinical trial
Susana Cuesta Frechoso,
Manuel Mene ´ndez, Cristina
Guisasola, Ignacio Arregui,
Jose ´ M Tejerina
and Alberto Sicilia
University of Oviedo, School of Stomatology,
Section of Periodontics, Oviedo, Spain
Cuesta Frechoso S, Mene ´ndez M, Guisasola C, Arregui I, Tejerina JM, Sicilia A:
Evaluation of the efficacy of two potassium nitrate bioadhesive gels (5% and 10%) in
the treatment of dentine hypersensitivity. A randomised clinical trial. J. Clin.
Periodontol 2003; 30:315–320. r Blackwell Munksgaard, 2003.
Abstract
Aim: A randomised clinical trial was designed to compare the immediate efficacy
(48–96 h) of two treatments with bioadhesive gels with different concentrations of
potassium nitrate (NK 5% versus NK 10%) on dentine hypersensitivity (DH). We
evaluated DH by means of the use of the evaporative stimulus (ES), as the main
outcome, using a placebo control group as reference.
Patients and Methods: Forty-five consecutive patients who, after stimulation with a
blast of air, had at least one tooth with DH X 2 according to the verbal ratings scale
(VRS) scale were selected. They were randomly treated with a bioadhesive gel with
5% NK, 10% NK or a placebo gel without NK. The DH was evaluated at baseline,
days 2, 4, 7 and 14 by an examiner blind to the procedure. The response to the ES with
a blast of air, to the tactile stimulation with a probe and the subjective evaluation of
the patient measured on the VRS scale were recorded. Statistical analysis was made
using the Kruskal–Wallis test.
Results: A greater reduction of DH after ES was observed after 48 h of treatment in
the NK10% group (35.8%) compared to the NK5% group and placebo group (11.8%
and 13.4%, respectively). This difference increased significantly at 96 h (p50.003).
No significant differences were observed for the other variables. These preliminary
results may support the usefulness of an NK 10% gel to reduce the DH after
stimulation with a blast of air during the first 4 days of its appearance.
Key words: bioadhesive gel; dentine
hypersensitivity; potassium nitrate
Accepted for publication 4 April 2002
Dentine hypersensitivity (DH) is a
painful response of the tooth to different
stimuli such as dental brushing, food or
thermal changes. The most common
complaint mentioned by the patient
is sensitivity to thermal stimuli, which
has been traditionally evaluated by
the use of a blast of air (Kanapka
1990). This is a threat to the dental
health of people who suffer this problem
as the pain can interfere with their
oral hygiene (Wycoff 1982). Numerous
agents have been used in DH therapy.
Potassium nitrate (NK), which was
introducedby Hodosh
accepted by the ADA (1986), is one of
the most frequently used agents at
present.
The mechanism of action of NK,
which is still unknown, appears to be of
(1974)and
neural type (Pashley 1986). The potas-
sium cation, which is the active part
(Kim 1986), tends to concentrate in the
interior of the dentinal tubules, causing
a depolarisation of the cellular mem-
brane of the nerve terminal and a
refractory period with decreased sensi-
tivity (Pashley et al. 1984, Markowitz &
Kim 1992). However, the role of its
occlusivecapacity ofthedentinal
J Clin Periodontol 2003; 30: 315–320
Printed in Denmark. All rights reserved
Copyright r Blackwell Munksgaard 2003

Page 2

tubules, although not very probable,
cannot be ruled out (Markowitz &
Kim 1992).
Several clinical studies have endorsed
the efficacy of NK, in toothpastes or
mouthwashes, as a desensitising agent
(Hodosh 1974, Green et al. 1977, Blong
et al. 1985, Nagata et al. 1994), with
significant results between the second
and fifth weeks (Reinhart et al. 1990,
Echeverrı ´a et al. 1991, Schiff et al. 1994,
Sicilia et al. 1996). Nevertheless, a few
studies exist which report contradictory
results (Green et al. 1977, Manoucher-
Pour et al. 1984).
According to these results, a need
exists for treatment, which relieves the
symptoms of DH in the first days of its
presentation (48–96 h). A little studied
presentation of NK has been in a gel
(Reinhart 1990). The gel containing
10% NK is a novel presentation about
which we have very little information.
The aim of the present study was to
compare, by means of a randomised,
triple blind, parallel, placebo controlled
study, the immediate efficacy (48–96 h)
of two types of NK gels (5% and 10%)
in the treatment of DII stimulated by a
blast of air, and to evaluate the fre-
quency of appearance of adverse effects
of these treatments.
Patients and Methods
A consecutive sample of 45 patients was
selected from the Section of Period-
ontics, School of Estomatology, Uni-
versity of Oviedo (Asturias, Spain)1and
two private clinics in the region. All
patients had to meet the following
inclusion criteria:
? Patients of either gender and over 18
years of age.
? DH in at least one tooth, with a
degree X2 on the verbal rating scale
(VRS), after stimulation with a blast
of air.
? All patients were adequately in-
formed and voluntarily agreed to
participate in the study.
Exclusion criteria were:
? The presence of caries or restoration
of any type in the tooth to be studied.
? The presence of occlusal overload or
occlusal adjustment recently made in
the tooth to be studied.
? Periodontal surgery in the area of the
tooth to be studied during the pre-
vious 3 months.
? Treatment with any product that
could influence the DH of the patient
in the 30 days prior to baseline.
? Previous history of hypersensitivity
reactions or specific oral allergy to
any of the components of the medica-
tions to be evaluated.
? Treatment with any of the medica-
tions to be evaluated in the 30 days
prior to baseline.
? Pregnancy or lactation.
? Systemic diseases that can interfere
with the collection of representative
data of the pathology to be studied.
A randomised, triple blind, parallel,
placebo controlled study was designed
(ADA 1986). The mean age of the
selected subjects was 47 years (range
23–76 years). Eighty-two percent (37)
were females. Ninety-one percent (41)
of the participants included citrus fruits
in their daily diet.
All patients who met the inclusion
criteria were randomly assigned to one
of three treatment groups: 10% NK
bioadhesive gel, 5% NK bioadhesive
gel and a placebo group (placebo
bioadhesivegel).
namely the one found to be the most
sensitive to the evaporative stimulus,
was selected by the examiner for each
patient (Fig. 1).
Participants were instructed to apply
the gel, using a cannula in order to
cover the area of exposed root. Applica-
Only onetooth,
tion was made twice a day, only on the
chosen tooth, immediately after dental
brushing, with a soft filament tooth-
brush and an experimental toothpaste
devoid of active principles. Participants
were also informed that they could not
use other products of oral hygiene or
treatment.
Neither the participants in the study
nor the investigators or the personnel
who made the statistical analysis knew
which of the three groups each patient
belonged to. The follow-up protocol of
each patient lasted 14 days, beginning
with a baseline clinical examination,
controls on days 2, 4 and 7, and a final
evaluation on day 14.
The procedures employed to compare
the clinical efficacy of the two treat-
ments were:
? The main outcome variable was to be
considered the evaporative stimulus
(ES), that is, the degree of sensitivity
perceived by the patient, when the
examiner applied a blast of air to the
tooth isolated with cotton wool rolls,
from a distance of 1 cm for 1 s
(Tarbet et al. 1979, Collins et al.
1984). The following VRS scale was
used: 05absence of pain, but per-
ceiving stimulus,
25pain during application of stimu-
lus, and 35pain during application
of stimulus and immediately after.
15slightpain,
Fig.1. Teeth selected by the examiner.
316
Cuesta Frechoso et al.

Page 3

? The subjective global evaluation of
the intensity of the episodes experi-
enced by the patient (GSE) (Tarbet et
al. 1980, Silverman 1986, Clark et al.
1987, Minkoff & Axelrod 1987), that
is, the degree or intensity of sensitiv-
ity experienced in their daily life
against usual stimuli, was evaluated
on a scale of 0–5 points (0 referring
to the absence of sensitivity and 5 to
maximum sensitivity).
? The tactile stimulation (TACS) (Col-
lins et al. 1984, Manoucher-Pour et
al. 1984, Silverman 1986), that is, the
sensitivity perceived by the patient
according to the above-mentioned
VRS scale, when the examiner lightly
touches the exposed radicular surface
of the tooth under study with a
periodontal probe.2The terms slight,
moderate or intense were used to
describe the maximum intensity of
adverse effects. The degree of treat-
ment compliance was evaluated by
means of the control of the volume of
gel consumed by each patient accord-
ing to the following scale:
? Correct (acceptable): real consump-
tion approximately greater than 80%
of the expected (weight of the tube at
the end of the studyo61.4 g).
? Regular (acceptable): real consump-
tion approximately from 60% to 80%
of the expected (weight of tube
between 61.4 and 62.8 g).
? Insufficient (not acceptable): real
consumptionapproximately
than 60% of the expected (weight of
tube greater than 62.8 g).
lower
Statistical Analysis
The relation observed between the re-
duction of DH evaluated by means of
ES, TACS and type of treatment was
analysed using the Kruskal–Wallis test.
The relation observed between DH
measured using subjective global evalua-
tion (GSE) and the type of treatment was
studied using the ANOVA test, when
normality of variables and homogeneity
of the variances could not be ruled out.
Results
In the analysis of the results obtained
after ES, clear reduction of symptoms in
the NK 10% group could be seen as
compared with the NK 5% group and
placebo group. This effect was more
marked in the 48–96 h after initiation of
treatment, with a 35.8% reduction in the
NK 10% group after the first 48 h of
treatment, a figure three times greater
than the NK 5% (11.8%) and placebo
groups (13.4%). At 96 h, the reduction
in the NK 10% group reached 66%, 2.3
times greater than the control group
treated with NK 5% (28.6%) and 1.9
times greater than the placebo group
(34.4%) (Fig. 2). These differences in
the scoring of the VRS reached 0.6
points at 48 h and range from 0.87 to
0.93 points at 96 h, these being
statistically significant (Table 1).
After 96 h the degree of DH in the
NK 10% group remained stable, the
gain achieved remaining the same for
up to 2 weeks (Fig. 2). The placebo and
NK 5% groups showed a reduction of
0.06 points and reached the values of
the NK 10% group at 2 weeks. At the
end of the study, noticeable differences
did not exist among the three groups,
although it was observed that NK 10%
reduced DH to a greater percentage
(Table 1, Fig. 2).
In relation to TACS and GSE, no
significant differences were seen after
48 h from the initiation of treatment in
the NK 10%, 5% and placebo groups
(Tables 2 and 3, Figs. 3 and 4). The
degree of compliance with treatment
was evaluated at the final visit, by
calculating the quantity of product
remaining. This was acceptable in the
majority of cases. In the NK 10% group,
compliance was correct
regular in 6.6% and insufficient in the
same percentage of patients (6.6%). In
the NK 5% group, compliance was
correct in 80%, regular in 13.4% and
insufficient in 6.6%. Compliance was
correct in 100% of the placebo group.
Two slightly adverse effects were
found: one in the subjects of the NK
10% group and the other in the placebo
group. These consisted of the appear-
ance of small irritations in the area of
the treated tooth, which disappeared
spontaneouslywithout
treatment.
in86.6%,
interrupting
Fig.2. Evolution of dentine hypersensitivity (DH) in the evaporative stimulus (ES)
evaluated according to the degree of sensitivity perceived on the VRS in the three groups
(NK 10%, NK 5% and placebo).
Table1. Reduction in the VRS for the evaporative stimulus (ES) in the three treatment groups
GroupnRed 1–2 Red 1–3Red 1–5
XðSDÞ
0.93 (0.60)
0.33 (0.81)
0.33 (0.62)
XðSDÞ
1.73 (0.70)
0.80 (0.77)
0.86 (0.74)
XðSDÞ
1.66 (1.11)
1.40 (0.98)
1.46 (0.74)
NK 10%
NK 5%
Placebo
15
15
15
Kolmogorov–Smirnov
Kruskal–Wallis test
p50.002
X257.872
gl52
p50.019
0.02
11.544
2
0.003
0.016
1.211
2
0.546
Red 1–2: Reduction of the ES response after 48 h from initiation of treatment. Red 1–3: Reduction
of the ES response after 96 h from initiation of treatment. Red 1–5: Reduction of the ES response at
the end of treatment.
DH treatment with NK gel
317

Page 4

Discussion
DH is a very common painful sensation,
difficult to solve, in spite of the fact that
a large variety of treatments exist. In
order for a product that has been
designed to reduce DH to be used in
clinical practice, it must be perceived by
both the professional and the patient as
being successful.
Neither the former will prescribe, nor
the latter will continue, a treatment that
does not relieve the discomforts or pain
experienced in an everyday situation.
One of the therapeutic agents more
frequently employed is NK. Its efficacy
as a desensitising agent, both in tooth-
pastes and in mouthwashes, has been
endorsed in numerous studies (Hodosh
1974, Green et al. 1977, Tarbet et al.
1982, Blong et al. 1985, Reinhart et al.
1990, Echeverrı ´a et al. 1991, Nagata et
al. 1994, Sicilia et al. 1996), showing a
significant reduction between the sec-
ond and fifth weeks of treatment.
There is a need to develop new
treatments or products, which permit
the relief of the symptoms of DH from
the first days of their appearance. Thus,
one of the fields to explore is the use of
bioadhesive gels, as in their pharma-
ceutical form these allow maximum
adherence to the oral surfaces, and
provide total precision in their applica-
tion. They could also be an ideal vehicle
for prolonging the gradual liberation
(substantivity) of NK in the area to be
treated.
In studies of this type, it is important
to bear in mind that tolerance to the
same pain can vary considerably among
different people, and even in the same
person depending on the time and
circumstances, since the perception of
pain depends on individual factors such
as personality, psychological factors
and educational level (Kanapka 1990).
Pain associated with DH has been
difficult to quantify and reproduce
(Blong et al. 1985). The threshold of
pain can vary by suggestion and by
changes in the emotional state of the
subject (Hodosh 1982). A series of
norms have been followed throughout
the study in order to minimise the
possible discrepancies introduced by
the above-mentioned factors in relation
to the results. However, it is impossible
to avoid their influence completely
(Echeverrı ´a et al. 1991).
Comparing the effect of the 10% NK
bioadhesive gel observed in our study
with the results obtained in other
studies, which have employed NK in
toothpastes and mouthwashes, it can be
seen that the reduction achieved in the
latter is much slower in time. With the
ES test the improvement became notice-
able with a 1% NK mouthwash in 14
days (Sicilia et al. 1996), obtaining a
reduction of 43.4%, which is compar-
able with the reduction we obtained at 2
days in this study with the 10%
bioadhesive gel (35%). With similar
methodology, in studies testing a 5%
NK toothpaste the improvement was
only obvious after 5 weeks of use with
respect to placebo (Echeverrı ´a et al.
1991) and after 6 weeks using NK
Table2. Reduction in the VRS for tactile stimulation (TACS) in the three treatment groups
Groupn Red 1–2Red 1–3Red 1–5
XðSDÞ
0.26 (1.1)
0.66 (0.61)
0.66 (0.61)
XðSDÞ
0.66 (1.17)
0.93 (0.7)
0.86 (0.74)
XðSDÞ
0.93 (1.03)
1.13 (0.91)
1.26 (0.8)
NK 10%
NK 5%
Placebo
15
15
15
Kolmogorov–Smirnov
Kruskal–Wallis test
p50.007
X251.778
gl52
p50.411
0.009
0.599
2
0.741
0.070
1.127
2
0.569
Red 1–2: Reduction of the TACS response after 48 h from initiation of treatment. Red 1–3:
Reduction of the TACS response after 96 h from initiation of treatment. Red 1–5: Reduction of the
at the response TACS at the end of treatment.
Fig.3. The evolution of dentine hypersensitivity (DH) in the tactile stimulation (TACS)
evaluated according to the degree of sensitivity perceived on the VRS in the three groups
(NK 10%, NK 5% and placebo).
Fig.4. Evolution of the global subjective evaluation (GSE) evaluated according to the VRS
in the three groups (NK 10%, NK 5% and placebo).
318
Cuesta Frechoso et al.

Page 5

toothpaste with a copolymer of methox-
yethylene and maleic acid and sodium
fluoride versus a placebo (Schiff et al.
1994). No information of the 48–96-h
results is available, as in these studies
the reduction of the levels of pain were
only evaluated after the first week of
treatment.
A previous study (Reinhart et al.
1990) has evaluated the efficacy of NK
10% gel and glycerine (a glycerine-
based 10%potassium
although important methodological dif-
ferences exist, which make the compar-
ison with our study difficult. The
response to the thermal stimulation with
cold water was evaluated in 12 patients
with generalised DH, in whom the gel
was applied with soft acrylic trays for 5
mins a day. A significant improvement
was not detected, a fact contrary to the
findings in our study, until the second
week in the NK 10% group. It is
important to emphasise the improve-
ment observed in the third week of the
group treated with placebo gel (glycer-
ine) in relation to the patients without
treatment. In our study we have ob-
served a positive response in the group
similar to that detected in the 5% NK
group, which, as no fourth group of
patients without treatment exists, pre-
vents us from ruling out the possible
therapeutic effect of the placebo in the
control group, or the real absence of the
effect of the NK 5% gel.
Studies have been made with stan-
nous fluoride gel, but the efficacy of
10% NK gel as an initial treatment of
DH appears to be greater, since the
former showed only a satisfactory effect
in the long term (Blong et al. 1985,
Thrash et al. 1994) while the 10% NK
gel reduced DH after 48 h of treatment.
The selection criterion of patients
was to have at least one tooth with
nitrate gel),
DH42 on the VRS. However, this can
produce a bias in the selection process,
which can justify the baseline differ-
ences observed in relation to the values
of other secondary variables studied.
Thus, we have found baseline differ-
ences in the degree of DH evaluated by
means of TACS between groups. This
together with the possible methodologi-
cal errors related to the test (Council of
Dental Therapeutics 1982, Collins et al.
1984) make the results of treatment
evaluated with TACS difficult to inter-
pret in our study. In the same way, on
selecting and treating only one tooth it
is difficult to evaluate the response to
treatment by means of one variable such
as GSE, which subjectively registers the
general perception that the patient has
of his/her mouth.
A placebo effect, similar to that
observed in other studies of DH (Pearce
et al. 1994, Silverman et al. 1996), was
also seen in our patients. Such an effect
must be justified with the natural
tendency toward spontaneous remission
of DH (Hodosh 1974). This preliminary
study appears to confirm the usefulness
of a 10% NK bioadhesive gel as a
treatment to reduce the DH stimulated
by a blast of air, in the 48–96 h of its
appearance, as it was more effective in
less time than the 5% NK gel and
placebo. However, its efficacy in a
medium term of 4 to 6 weeks needs to
be established in other studies.
Acknowledgments
We wish to thank LACER S.A. for
sponsorship and technical support. We
are also grateful to the dental hygiene
team fortheircooperation
study (Almudena Mene ´ndez, Luis Sua ´r-
ez, CatalinaGarcı ´a,
Carmen delRı ´o,
in the
AnaZapico,
Lozano, Begon ˜a
Rosario Prieto, Dolores Gonza ´lez, Ma
Jose ´ Buznego) and to David H. Wallace
for the final correction of the manuscript.
Zusammenfassung
Untersuchung der Effektivita ¨t zweier bioadha ¨-
siver Kaliumnitrat-Gele (5% und 10%) zur
Behandlung derDentinu ¨berempfindlichkeit.
Eine randomisierte klinische Studie
Zielsetzung: Vergleich der unmittelbaren (48–
96 Stunden) Effektivita ¨t zweier bioadha ¨siver
Kaliumnitrat-Gele von unterschiedlicher Kon-
zentration (NK5% und NK10%) zur Behan-
dlung von Dentinu ¨berempfindlichkeit (DU¨) in
einer randomisierten plazebokontrollierten kli-
nischen Studie.
Patienten und Methoden: 45 konsekutive
Patienten, die nach Stimulation mit einem
Luftsto? (Verdunstungsstimulus [VS]) an zu-
mindest einem Zahn eine DU¨X2 auf einer
VRS-Skala zeigten, wurden fu ¨r die Studie
ausgewa ¨hlt. Diese Patienten wurden in rando-
misierter Reihenfolge mit einem der beiden
bioadha ¨siven Gele mit 5% NK, 10% NK oder
einem Plazebogel ohne NK behandelt. Die DU¨
wurde zu Beginn der Studie und nach 2, 4, 7
und 14 Tagen durch einen gegenu ¨ber der
Therapie verblindeten Untersucher bestimmt.
Die Reaktion der Patienten auf den Verdun-
stungsreiz durch einen Luftsto?, den taktilen
Reiz mit einer Sonde und deren subjektive
Empfindung gemessen auf einer VRS-Skala
wurden dokumentiert. Die statistische Auswer-
tung erfolgte mit dem Kruskal-Wallis-Test.
Ergebnisse: 48 Stunden nach Behandlung
wurde in der NK10%-Gruppe eine gro ¨?ere
Reduktion (35.8%) der DU¨nach VS beobachtet
als in der NK5%- (11.8%) und der Plazebo-
gruppe (13.4%). Dieser Unterschied vergro ¨?erte
sich signifikant nach 96 Stunden (p50.003).
Fu ¨r die anderen Variablen wurden keine
signifikanten Unterschiede beobachtet.
Schlussfolgerungen: Diese vorla ¨ufigen Ergeb-
nisse unterstu ¨tzen den Nutzen eines 10%igen
Kaliumnitrat-Gels zur Reduktion der DU¨ auf
Stimulation mit einem Luftsto? wa ¨hrend der
ersten 4 Tage nach deren Auftreten.
Re ´sume ´
Evaluation de l’efficacite ´ de deux gels bio-
adhe ´sifs de nitrate de potassium (5% et 10%)
pour le traitement de l’hypersensibilite ´ denti-
naire. Une e ´tude clinique randomise ´e.
But: Une e ´tude clinique randomise ´e fut mise au
point pour comparer l’efficacite ´ imme ´diate (48–
96 heures) de deux traitements a ` base de gels
bio-adhe ´sifs a ` diffe ´rentes concentrations de
nitrate de potassium (NK5% contre NK10%)
sur l’hypersensibilite ´ dentinaire (DH). Nous
avons e ´value ´ la DH au moyen de l’utilisation du
stimulus evaporatif (ES), en tant que conse ´-
quence principale et un groupe placebo comme
re ´fe ´rence.
Patients and Methods: 45 patients conse ´cutifs
qui, apre `s stimulation avec un jet d’air pre ´-
sentaient au moins une dent avec une DH
supe ´rieure ou e ´gale a ` 2 selon l’e ´chelle VRS
furent se ´lectionne ´s. Ils furent traite ´s au hasard
Table3. Dentine hypersitivity (DH) reduction among visits as measured by Global subjective
evaluation (GSE)
GroupnRed 1–2 (n)Red 1–3 (n) Red 1–5 (n)
XðSDÞ
1.0 (1.25)
0.73 (0.96)
1.13 (1.59)
XðSDÞ
2.2 (1.65)
1.93 (1.62)
1.73 (1.38)
XðSDÞ
2.53 (1.76)
2.06 (1.27)
2.60 (1.49)
NK 10%
NK 5%
Placebo
15
15
15
Kolmogorov–Smirnov
Kruskal–Wallis test
P50.004
X250.493
gl52
P50.782
0.118
0.684
2
0.710
0.187
1.531
2
0.465
nRed 1–2: Reduction of HD 48 hours after initiation of treatment as measured by GSE. Red 1–3:
Reduction of HD 96 hours after initiation of treatment as measured by GSE. Red 1–5: Reduction of
HD at the end of treatment as measured by GSE.
DH treatment with NK gel
319