dentistry journal

Article
Pilot Study of a New Mandibular Advancement Device
Marzia Segù 1 , Giovanna Campagnoli 2 , Marco Di Blasio 1 , Antonio Santagostini 1, * , Matteo Pollis 3
and Luca Levrini 4

1 Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; [email protected] (M.S.);
[email protected] (M.D.B.)
2 Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Section of Dentistry of Pavia,
University of Pavia, 27100 Pavia, Italy; [email protected]
3 School of Dentistry, University of Siena, 53100 Siena, Italy; [email protected]
4 Department of Human Sciences, Innovation and Territory, Postgraduate School of Orthodontics,
School of Dental Hygiene, University of Insubria, 22100 Como, Italy; [email protected]
* Correspondence: [email protected]; Tel.: +39-3394538461

Abstract: This study was conducted to determine the efficacy of a customized mandibular advance-
ment device (MAD) in the treatment of obstructive sleep apnea (OSA). Eight patients (M = 3; F = 5;
mean age = 56.3 ± 9.4) with a diagnosis of OSA confirmed by polysomnography (PSG) were re-
cruited on the basis of the following inclusion criteria: apnea-hypopnea index (AHI) > 5, age between
18 and 75 years, body mass index (BMI) < 25, and PSG data available at baseline (T0). All were treated
with the new NOA® MAD by OrthoApnea (NOA® ) for at least 3 months; PSG with NOA in situ was
performed after 3 months of treatment (T1). The following parameters were calculated at T0 and T1:
AHI, supine AHI, oxygen desaturation index (ODI), percentage of recording time spent with oxygen
saturation <90% (SpO2 < 90%), and mean oxygen desaturation (MeanSpO2%). Data were submitted
for statistical analysis. The baseline values were AHI = 21.33 ± 14.79, supine AHI = 35.64 ± 12.80,
ODI = 17.51 ± 13.5, SpO2 < 90% = 7.82 ± 17.08, and MeanSpO2% = 93.45 ± 1.86. Four patients had
mild OSA (5 > AHI < 15), one moderate OSA (15 > AHI < 30), and three severe OSA (AHI > 30). After
treatment with NOA® , statistically significant improvements in AHI (8.6 ± 4.21) and supine AHI
Citation: Segù, M.; Campagnoli, G.;
(11.21 ± 7.26) were recorded. OrthoApnea NOA® could be an effective alternative in the treatment of
Di Blasio, M.; Santagostini, A.; Pollis,
OSA: the device improved the PSG parameters assessed.
M.; Levrini, L. Pilot Study of a New
Mandibular Advancement Device.
Dent. J. 2022, 10, 99. https://doi.org/
Keywords: obstructive sleep apnea; mandibular advancement devices; polysomnography
10.3390/dj10060099

Academic Editor: Nikolaos Gkantidis

Received: 7 April 2022 1. Introduction

Accepted: 17 May 2022 Obstructive sleep apnea (OSA) is a breathing disorder characterized by repeated
Published: 6 June 2022 collapse, total or partial, of the upper airway during sleep [1]. A recent systematic review
Publisher’s Note: MDPI stays neutral
indicated that OSA may affect nearly 1 billion adults aged 30–69 years, and the number
with regard to jurisdictional claims in with moderate to severe OSA was estimated to be almost 425 million [1]. However, most
published maps and institutional affil- cases of OSA remain undiagnosed and untreated [1].
iations. Treatments for OSA include the use of continuous positive airway pressure (CPAP)
devices that, by blowing air into the upper airway, reverse the collapse and end the apnea
event [2]. Although CPAP remains the gold standard treatment in moderate-to-severe
OSA, the use of a mandibular advancement device (MAD) is also considered effective,
Copyright: © 2022 by the authors. especially in mild-to-moderate OSA and in cases of low adherence to CPAP therapy [2].
Licensee MDPI, Basel, Switzerland. A MAD increases the upper airway space and reduces the risk of obstruction by pulling
This article is an open access article the jaw and tongue forward. The method has been shown to reduce by 50% the number of
distributed under the terms and PSG-detected apnea-hypopnea events per hour (i.e., the apnea-hypopnea index, AHI) and
conditions of the Creative Commons
achieve higher patient compliance compared with CPAP [3].
Attribution (CC BY) license (https://
A MAD can be prefabricated or custom-made. Customized devices are titratable and
creativecommons.org/licenses/by/
have been reported to show higher comfort and compliance [3–6]. They have also been
4.0/).

Dent. J. 2022, 10, 99. https://doi.org/10.3390/dj10060099 https://www.mdpi.com/journal/dentistry

Dent. J. 2022, 10, 99 2 of 10

shown to be more effective and stable [3,7,8]. Vanderveken et al., comparing the efficacy of a
customized versus a prefabricated device, found greater compliance and effectiveness with
the custom-made appliance, while the thermoplastic MAD did not obtain a therapeutic
effect due to lack of retention and lower comfort for the patients [4].
In the present study, a new MAD is evaluated. MAD is a custom-made, two-piece
device designed using CAD-CAM technology to be smaller and less cumbersome than ex-
isting devices. It is designed for the individual patient on the basis of a detailed mandibular
kinematic evaluation. It allows titration of the protrusive movement and can be reinforced
for patients with bruxism. Since the relationship between the degree of mandibular pro-
trusion and mouth opening influences the efficacy of this treatment, MAD is designed to
ensure effective protrusion associated with reduced muscular discomfort.
This study aims to evaluate the effectiveness of new MAD in the treatment of OSA.
The null hypothesis is that the new appliance is not associated with a significant
improvement of the selected PSG parameters.

2. Materials and Methods

2.1. Patient Selection
The study was approved by the Unit Internal Review Board (17-1023).
All the patients involved in the study were selected by a dentist with expertise in
sleep medicine on the basis of medical, psychological, and dental criteria. Individuals
aged between 18 and 75 years with a body mass index (BMI) < 25, an AHI > 5, and a
PSG-confirmed diagnosis of mild to severe OSA were eligible; all had previously refused
CPAP treatment [9].
All prospective participants underwent a complete history and physical examination.
Those with an unsuitable stomatognathic situation (fewer than 8 teeth per arch, temporo-
mandibular disorder, periodontitis), central sleep apnea, or cardiovascular diseases were
excluded. Pregnancy (from the third month of pregnancy to three months after delivery)
was a further exclusion criterion.
In order to evaluate patient satisfaction, each step of the protocol was followed by
the administration of a detailed questionnaire collecting information about symptoms,
perception of treatment efficacy, side effects (rated in terms of frequency and severity), and
adherence to the treatment. The questionnaire also included the Epworth Sleepiness Scale
and the Berlin Questionnaire to assess snoring, daytime sleepiness, fatigue, hypertension,
and BMI.
Baseline PSG (T0) was compared with PSG after 3 months with the appliance in situ
(T1), focusing on the following PSG respiratory parameters: AHI (mean number of apnea
and hypopnea events per hour of sleep), supine AHI (mean number of apnea and hypopnea
events per hour of sleep in the supine position), oxygen desaturation index (ODI), mean
oxygen saturation (MeanSpO2), and hypoxemia index, i.e., the percentage of recording
time spent with oxygen saturation <90% (SpO2 < 90%).
Patients read and signed an informed consent document prior to being enrolled in
this study.
Sample: Eight patients with symptomatic OSA met the study criteria and were en-
rolled. They were prevalently females (5 females, 3 males) and generally middle aged
(mean age: 56.25 ± 9.75 years). OSA was mild (5 ≥ AHI < 15), moderate (15 ≥ AHI < 30),
and severe (AHI ≥ 30) in 4, 1, and 3 patients, respectively. At T0, the patients’ mean res-
piratory variables were AHI: 21.33 ± 14.79, Supine AHI: 35.64 ± 12.80, ODI: 17.51 ± 13.5,
SpO2 < 90%: 7.82 ± 17.08, MeanSpO2: 93.45 ± 1.86.

2.2. Device
The oral appliance chosen for this study was NOA® by OrthoApnea, a new titratable,
custom-made, two-piece MAD with interconnected vertical extensions. The appliance
comprises a maxillary bite and several mandibular bites that allow for sequential degrees
of protrusion. The device is made of polyamide-12 through 3D printing with CAD-CAM
Dent. J. 2022, 10, x FOR PEER REVIEW 3 of 10

Dent. J. 2022, 10, 99 3 of 10

of protrusion. The device is made of polyamide-12 through 3D printing with CAD-CAM

technology, which allows reducing its size. NOA® allows the patient a wide range of jaw
technology, which allows reducing its size. NOA® allows the patient a wide range of jaw
movements (Figure 1).
movements (Figure 1).

Figure1.1.The
Figure Thedevice
deviceworn
wornbyby the
the patient.
patient.

2.3.
2.3. Study
StudyDesign
Design
The
Thefirst
firststep
stepofofthe
theprotocol
protocolconsisted
consisted of all thethe
of all preliminary
preliminary medical, dental,
medical, and and
dental,
neurological analyses, including evaluation of baseline PSG data and administration of
neurological analyses, including evaluation of baseline PSG data and administration of
questionnaires. TMJ clinical examination according to DC/TMD Axis I was performed [10].
questionnaires. TMJ clinical examination according to DC/TMD Axis I was performed
Disease severity was defined by the AHI.
[10].InDisease severity
the second step,was defined
eligible by the
patients wereAHI.
treated with NOA® to test their tolerance of
the device and, therefore, their likely response totreated
In the second step, eligible patients were this MAD with NOA® to test their tolerance of
therapy.
the device and,
An initial therefore,period
habituation their likely responseduring
was envisaged to thiswhich
MAD the therapy.
patient kept the device
Anmouth
in their initial habituation periodofwas
for short periods timeenvisaged
while awake.during which thethe
Thereafter, patient kept
device wastheput
device
in at
in their mouthand
bedtime for worn
short periods
throughout of time while awake.
the night. Thereafter,
Advancement the device
(titration was was
protocol) put in at
bedtime and activated
progressively worn throughout the night.
by the dentist Advancement
until clinical resolution(titration protocol)
of subjective was progres-
symptoms [11].
®
sively activated PSG
A follow-up by the dentist
with NOA until clinical
in situ resolutionafter
was performed of subjective
3 months ofsymptoms [11].
treatment [12,13].
Statistical
A follow-up analysis: Descriptive
PSG with NOA®statistics (mean,
in situ was standard after
performed deviation, median,
3 months mini-
of treatment
mum and maximum values) were calculated. The normality of the data was calculated
[12,13].
usingStatistical
the Kolmogorov-Smirnov test. Subsequently,
analysis: Descriptive to analyze
statistics (mean, standardthe results obtained
deviation, withmini-
median,
the NOA ® , paired Student t-tests were performed to compare AHI, supine AHI, ODI,
mum and maximum values) were calculated. The normality of the data was calculated
SpO2 < 90%, and MeanSpO2% between T0 and T1. For all tests, the level of significance
using the Kolmogorov-Smirnov test. Subsequently, to analyze the results obtained with
was set at p® < 0.05.
the NOA , paired Student t-tests were performed to compare AHI, supine AHI, ODI,
SpO2 < 90%, and MeanSpO2% between T0 and T1. For all tests, the level of significance
3. Results
was set at p < 0.05. ®
Efficacy of the OrthoApnea NOA Device
Eight patients (3 males, 5 females; mean age: 56.25 ± 9.75 years) consented to use the de-
3. Results
vice. Their respiratory index values at T0 were AHI: 21.33 ± 14.79, supine AHI: 35.64 ± 12.80,
Efficacy
ODI: of the
17.51 OrthoApnea
± 13.5, NOA7.82
SpO2 < 90%:
® Device
± 17.08 and MeanSpO2: 93.45 ± 1.86. Four had mild
(5 ≥ AHI
Eight patients
< 15), (3 males,(15
one moderate ≥ AHI <mean
5 females; age:three
30), and 56.25 ± 9.75
severe ≥ 30)
years)
(AHI consented to use
OSA (Table 1). the
device. Their respiratory index values at T0 were AHI: 21.33 ± 14.79, supine AHI: 35.64 ±
12.80, ODI: 17.51 ± 13.5, SpO2 < 90%: 7.82 ± 17.08 and MeanSpO2: 93.45 ± 1.86. Four had
mild (5 ≥ AHI < 15), one moderate (15 ≥ AHI < 30), and three severe (AHI ≥ 30) OSA (Table
1).
Dent. J. 2022, 10, x FOR PEER REVIEW 4 of 10

Dent. J. 2022, 10, 99 4 of 10

Table 1. Characteristics of the whole population at baseline (T0).

Number of patients of the whole population at baseline (T0).

Table 1. Characteristics 8
Males 3
Number of patients 8
Females 5
Males 3
Age, mean ± SD
Females 56.25 ± 9.755
OSAS
Age, severity,
mean ± SD number of patients 56.25 ± 9.75
OSAS
Mild (5 severity,
≥ AHI <number
15) of patients 4
Mild (5 ≥ AHI < 15) 4
Moderate (15 ≥ AHI < 30) 1
oderate (15 ≥ AHI < 30) 1
Severe
Severe(AHI
(AHI≥≥30)30) 3 3
AHI
AHI 21.33 ± 14.79
21.33 ± 14.79
SupineAHI
Supine AHI 35.6435.64 ± 12.80
± 12.80
ODI
ODI 17.51
17.51 ± 13.5± 13.5
SpO2 < 90% 7.82 ± 17.08
SpO2 < 90%
MeanSpO2%
7.82 ±93.45
17.08
± 1.86
MeanSpO2% 93.45 ± 1.86
Two patients considered the device uncomfortable and decided not to continue with
Two patients considered the device uncomfortable and decided not to continue with
the therapy.
the therapy.
The remaining six patients were analyzed both at T0, before the treatment started, and
afterThe remaining
a minimum six patients
3-month werewith
treatment analyzed both (T1)
the device at T0, before
(Table 2). the treatment started,
and after a minimum 3-month treatment with the device (T1) (Table 2).
Table 2. Short-term effects of the appliance on respiratory variables in the six patients who continued
Table 2. Short-term effects of the appliance on respiratory variables in the six patients who contin-
with the therapy.
ued with the therapy.
T0 T1 p
T0 T1 p
AHI
AHI 21.33 ±
21.33 9.75
±9.75 8.6 ±±4.21
8.6 4.21 0.008
0.008
Supine AHI
Supine AHI 35.64 ±±12.80
35.64 12.80 11.21 ±±7.26
11.21 7.26 0.002
0.002
ODI
ODI 17.51 ±±13.5
17.51 13.5 8.81 ±±4.59
8.81 4.59 0.07
0.07
SpO2
SpO2 <<90%
90% 7.82
7.82 ±±17.08
17.08 0.66
0.66 ±±1.43
1.43 0.17
0.17
MeanSpO2
MeanSpO2 93.45
93.45 ±1.86
± 1.86 93.66 ± 1.03
93.66 ± 1.03 0.82
0.82

Paired t-tests showed statistically significant differences in AHI at T0 vs. T1 (Figure

Paired t-tests showed statistically significant differences in AHI at T0 vs. T1 (Figure 2)
2) or in supine AHI at T0 vs. T1 (p < 0.05) (Figure 3). No statistically significant differences
or in supine AHI at T0 vs. T1 (p < 0.05) (Figure 3). No statistically significant differences
were found in ODI, SpO2, and SpO2 < 90%. Table 2 details the short-term effects of treat-
were found in ODI, SpO2, and SpO2 < 90%. Table 2 details the short-term effects of
ment with NOA® on the PSG respiratory parameters analyzed.
treatment with NOA® on the PSG respiratory parameters analyzed.

Figure 2. A paired data t-test showed a significant difference between AHI at T0 and T1 (p < 0.05)
when evaluating data from patients (PZ) treated with the OrthoApnea NOA® device.
Dent. J. 2022, 10, x FOR PEER REVIEW 5 of 10

Dent. J. 2022, 10, 99 Figure 2. A paired data t-test showed a significant difference between AHI at T0 and5 of
T110(p < 0.05)
when evaluating data from patients (PZ) treated with the OrthoApnea NOA device.
®

Figure 3. A paired data t-test showed a significant difference between supine AHI recorded at T0
Figure 3. A paired data t-test showed a significant difference between supine AHI recorded at T0
and T1 (p < 0.05) in patients (PZ) using the OrthoApnea NOA® device.
and T1 (p < 0.05) in patients (PZ) using the OrthoApnea NOA® device.
Regardless of the severity of their OSA, all six patients met the AHI and supine AHI
Regardless
criteria of the severity
defining treatment success.ofIntheir OSA,
supine allthey
AHI, six patients met the AHI
showed reductions and from
ranging supine AHI
criteria
−17% todefining
−86% and treatment success.
in AHI from −37%In tosupine AHI, 3).
−91% (Table they showed reductions ranging from
−17% to −86% and in AHI from −37% to −91% (Table 3).
Table 3. Short-term effects of the appliance: changes in AHI and supine AHI.
Table 3. Short-term effects of the appliance: changes in AHI andChanges
supine AHI.
in Supine AHI
Patients Changes in AHI T0–T1
T0–T1
Changes in Supine AHI
Patients1 Changes in AHI−T0–T1
46% −75%
T0–T1
2 −91% −86%
1 −46% −75%
3 −67% −17%
2 −91% −86%
4 −37% −46%
3 −67% −17%
4 5
−37% −68% −−46%
86%

5 6 −68% −47% −−86%

57%

6 −47% −57%
One patient was reported to have AHI and supine AHI values < 5, which were
considered non-pathological.
One patient was reported to have AHI and supine AHI values < 5, which were con-
sidered non-pathological.
4. Discussion
Recent years have seen a growing interest in OSA in different fields of medicine due
4.
to Discussion
its considerable prevalence [14] and its important role as a risk factor for cardiovascular
and metabolic disorders
Recent years have[15].
seen a growing interest in OSA in different fields of medicine due
Although CPAP remains the gold standard treatment for OSA [16,17], MAD treatment
to its considerable prevalence [14] and its important role as a risk factor for cardiovascular
has emerged as an increasingly valuable alternative on account of its higher compliance and
and metabolic
remarkable disordersin[15].
effectiveness mild-to-moderate cases. MAD treatment is widely reported to
Although
reduce the severityCPAP remains
of several OSAthe gold standard
parameters treatment
in the long term, suchforasOSA [16,17],
the AHI, ODI,MAD
and treat-
ment
minimumhas emerged as an increasingly
oxygen saturation valuable alternative
[18–20]. Improvements in daytimeon accountand
sleepiness of its higher compli-
subjective
ance and remarkable
perception effectiveness
of snoring were reported inin mild-to-moderate
several cases.
studies [8,21–25]. MADCPAP
Although treatment
therapyis widely
was foundto
reported toreduce
be morethe
effective in reducing
severity daytime
of several OSAsleepiness
parameters in the
in long term term,
the long [24], MAD
such as the
treatment
AHI, ODI,achieved better therapeutic
and minimum compliance[18–20].
oxygen saturation [26–28]; instead, the two methods
Improvements proved
in daytime sleepiness
and subjective perception of snoring were reported in several studies [8,21–25]. Although
CPAP therapy was found to be more effective in reducing daytime sleepiness in the long
Dent. J. 2022, 10, 99 6 of 10

comparable in terms of improved quality of life, cognitive performance, and physical

function, also in the long term.
For these reasons, further research into MAD treatment appears warranted.
The wide variability in the response to treatment needs a strict control in each phase
of the therapy [29–31]. The literature proposes different methods to distinguish responders
and not responders, among which DISE-SAM protocol [32] and trial MAD [13]. Adequate
follow-up [20,33,34] is essential for evaluating the efficacy of the therapy as well as for
monitoring side effects related to long-term MAD use. The present study aims to test
a definitive MAD that introduces the concept of maximum customization. NOA® , by
OrthoApnea, is a two-piece, custom-made device designed using CAD-CAM technology.
The appliance offers the possibility to titrate the protrusive movement, which is crucial
for maximizing the therapeutic effect; furthermore, NOA® is designed for the individual
patient on the basis of a detailed mandibular kinematic evaluation in order to achieve
maximum comfort and compliance.
The results of our study showed statistically significant changes in AHI and supine
AHI values at T1 compared with T0 (p < 0.05). Conversely, no statistically significant
changes were found in ODI scores (p > 0.05), SpO2 < 90%, or MeanSpO2% (p > 0.05)
(Table 2).
According to the literature, a MAD can be considered effective if it leads to an at least
50% reduction in the AHI [21,35]. The NOA® by OrthoApnea met this criterion, leading to
statistically significant improvements (reductions) of around 59% in both AHI and supine
AHI. A review by Marklund et al. [21] found that MAD treatment reduced AHI values by
at least 50%: the treatment was deemed successful (success being defined as an AHI < 5) in
17–75% of patients, while AHI values < 10 were reported in 30–94% of the patients in all the
studies considered. De Britto Texeira and colleagues [36] reported that thanks to the use of
a suitably modified twin block device, 47% of their OSA sample obtained a 50% reduction
in AHI, while in 26%, the parameter returned to normal values. In a study conducted by
Duràn-Cantolla [24], 47% of the sample obtained a significant reduction in AHI. Overall,
the patients in this study quickly adapted to the NOA® ; in one case, treatment adherence
was undermined by discomfort associated with the device, while a further patient used the
device incorrectly and therefore failed to follow the therapeutic protocol. These findings
underline the importance of considering the influence of patient-dependent variables,
above all compliance, which is decisive in achieving therapeutic success.
The literature agrees that the side effects initially associated with MAD use are mostly
transient and can be resolved simply by modifying certain features of the device. In several
studies, the side effects associated with the initial phase of MAD therapy did not lead to
discontinuation of the treatment by the patient. In the sample examined by Milano and
colleagues [25], for example, some patients experienced side effects in the first month of
treatment, such as temporomandibular joint discomfort, difficulty chewing in the morning,
and dental tenderness; however, none of these problems precluded continued use of
the device.
The literature shows that personalized devices, such as NOA® by OrthoApnea, are
associated with greater patient-perceived comfort and better therapeutic outcomes than
prefabricated devices, these better outcomes being a result of greater adherence to the
treatment. According to an AADMS (American Academy of Dental Sleep Medicine) report,
systematic reviews have shown that personalized devices compare better to prefabricated
non-customizable ones. Partly because they provide more significant and better retention,
they are able to keep the jaw in a more stable position; consequently, they are more
effective and comfortable [37]. Guidelines on the clinical management of OSAS with oral
devices, published by the AADMS [3], recommend the prescription of a personalized and
titratable MAD rather than the prefabricated, non-titratable type. The literature evidence
shows that the former type is more effective than the latter in improving AHI and other
cardiorespiratory parameters. The 2014 TOMADO crossover study [5] compared the
efficacy of three different types of monoblock MAD in a sample of 90 patients. Although
Dent. J. 2022, 10, 99 7 of 10

the three types gave positive and comparable results, the non-personalized thermoplastic
device was the least comfortable due to poorer retention; this led to lower therapeutic
adherence compared with the semi-personalized and personalized devices.
In our study, 75% of the sample treated with NOA® accepted the device and followed
the treatment protocol without experiencing the problems commonly related to the use of
MADs. This could be due to the refined, customized design of this device outlined above.
However, to confirm this scientifically, it would be necessary to compare NOA® with other
custom-made MADs and enlist a larger sample of patients.
Mandibular advancement devices are capable of improving health and quality of
life, including social life [6,26], and thanks to their therapeutic efficacy in treating severe
OSAS, MAD therapy is suitable for all patients refusing CPAP. A meta-analysis conducted
by Schwartz [26] in 2018 showed a difference in treatment compliance between the two
therapies: with CPAP, it was 1.1 h per night lower than with MAD (p = 0.004). This explains
why CPAP does not show significant quality-of-life improvements compared with MAD
therapy, specifically significantly improved cognitive and functional results. This is despite
CPAP being more effective in improving cardiorespiratory parameters.
The present study does not have enough data to obtain statistically significant results
regarding the follow-up of the patients beyond the 3-month (T1) assessments. However,
numerous studies in the literature attest to the effectiveness of personalized MADs in
improving OSAS symptoms over time [18,19,21,31]. The most significant studies in this
regard include one conducted by Uniken Venema and colleagues in 2020 [20]. These
authors set out to compare the long-term effectiveness of CPAP and MAD in patients with
OSAS through evaluation of the effects of treatments over ten years. Polysomnography
results showed a favorable outcome of both therapies at ten years: the mean AHI in the
MAD group was 9.9 ± 10.3 events/h, versus 3.4 ± 5.4 events/h in the CPAP group. Both
therapies led to a substantial improvement in self-reported neurobehavioral outcomes at
ten years of follow-up. Attali and colleagues [19] also showed that MADs can effectively
treat OSAS in the long term, maintaining good compliance and patient satisfaction. Their
study, conducted in a sample of 279 patients with an average age of 58 years and followed
up for at least 1000 days, showed that 63% of the sample (at 2.5 years) continued treatment
with MAD with adequate efficacy, tolerability, and compliance over time; only in some
patients was a recurrence of side effects observed, probably due to the natural course of the
disease or to wear and tear of the MAD associated with a loss of therapeutic efficacy.

Limitations and Future Perspectives

Our study was limited mainly by the short follow-up time, the small sample size and
the lack of a control group (no treatment/other MAD). These limitations might be overcome
by recruiting a larger sample and extending the therapeutic monitoring time, controlling
for a series of time-dependent variables. Since OSAS is a chronic disease that can worsen
over time, it is important to maintain a constant improvement as the treatment progresses;
OSAS is also a risk factor for a series of systemic diseases, meaning that patients’ general
health also needs to be monitored. In some cases, clinicians may consider reinforcement of
behavioral therapy and sleep hygiene measures in order to address negative habits.
In addition, since there is no standardized titration protocol, it would be appropriate in
future research to evaluate whether the level of mandibular advancement determined by the
MAD corresponds to the individual therapeutic window. Dieltjens et al. [30] conducted an
exhaustive review of the titration techniques in use, especially the “trial and error” method
that is currently the most popular. This method involves selecting a particular mandibular
protrusion setting and evaluating its side effects and associated benefits, thereafter reaching
the individual therapeutic window by process of trial and error. With the OrthoApnea
NOA® system, too, the patient is required to follow a protrusive sequence established in
advance, in this case, on the basis of individual variables. The device includes a series of
lower splints that reproduce the established protrusive line, allowing the patient gradually
to reach his/her own most effective level of mandibular advancement. To motivate the
Dent. J. 2022, 10, 99 8 of 10

patient and enhance the therapeutic alliance, and therefore allow the therapeutic window to
be reached, the personalized titration protocol should be carefully explained to the patient.
Finally, the device requires some maintenance since it can deteriorate over time,
leading to a reduction in retention, comfort, and therapeutic efficacy. Again, to maintain
patient compliance and the effectiveness of the treatment, periodic re-evaluation of the
device is recommended so that any necessary modifications or replacements can be made.

5. Conclusions
Treatment with NOA® could be an effective alternative in the treatment of OSAS,
having been found to significantly improve some PSG respiratory parameters, specifically
AHI and supine AHI, even in cases of severe OSAS (AHI > 15). The other parameters
investigated (ODI, SpO2 < 90%, and MeanSpO2) also improved, albeit not significantly.
In conclusion, although the statistical data are promising, to establish the potential of the
device, further studies are needed.

Author Contributions: Conceptualization, M.S.; methodology, M.S.; software, M.P.; validation, M.S.;
formal analysis, G.C.; investigation, G.C.; resources, A.S.; data curation, M.P.; writing—original draft
preparation, G.C.; writing—review and editing, A.S.; visualization, M.D.B.; supervision, L.L.; project
administration, M.S.; funding acquisition, M.S. All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was approved by the Unit Internal Review
Board (17-1023).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: All data are available upon request to the corresponding author.
Conflicts of Interest: The authors declare that they have no conflict of interest.

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