Impact of Maxillomandibular Advancement Upon the Pharyngeal Airway Volume and the Apnea-hypopnea Index in the Treatment of Obstructive Sleep Apnea
Phase: NA
Conditions: OSA, OSAS, Apnea, Obstructive Sleep, Orthognathic Surgery
Sponsor: Centro Medico Teknon

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OSAS-OS Protocol v1.0 October 30, 2017 – Confidential 
 
Impact of Maxillomandibular Advancement Upon the 
Pharyngeal Airway Volume and the Apnea-hypopnea 
Index in the Treatment of Obstructive Sleep Apnea. 
 
 
 
PROTOCOL VERSION 1.0 
OCTOBER 30, 2017 
 
 
RUNNING TITLE: OSAS-OS - Maxillomandibular Advancement in the Treatment of 
Obstructive Sleep Apnea 
 
 
 
NCT No:  NCT03796078 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TITLE: Impact of Maxillomandibular Advancement Upon the Pharyngeal Airway 
Volume and the Apnea-hypopnea Index in the Treatment of Obstructive Sleep 
Apnea 
 
RUNNING TITLE: OSAS-OS - Maxillomandibular Advancement in the Treatment of 
Obstructive Sleep Apnea 
 
Date: 30.10.2017 
Version: V1.0 
AUTHORS: 
Maria Giralt-Hernando DDS, MSc * 1 a Adaia Valls-Ontañón MD, DDS, PhD * 1,2 b 
Orion Luiz Haas Jr 1,2,3 
Federico Hernández-Alfaro MD, DDS, PhD, FEBOMS 1,2 c 
* Maria Giralt-Hernando and Adaia Valls-Ontañón contributed equally to this work. 
1. Department of Oral and Maxillofacial Surgery, Clinical instructor (a), Associate (b) and Full 
Professor/Head (c), International Master in Oral Surgery (IMOS), Universitat Internacional de 
Catalunya (UIC), Barcelona, Spain. 
2. Institute of Maxillofacial Surgery, Teknon Medical Center, Barcelona, Spain. 
3. Department of Oral and Maxillofacial Surgery, Pontificial Catholic University of Rio Grande do 
Sul – PUC/RS, Rio Grande do Sul, Brazil. 
Corresponding author 
Dr. Maria Giralt DDS, MSc 
Clinical Instructor, Department of Oral and Maxillofacial Surgery 
Universitat Internacional de Catalunya 
Josep Trueta s/n 
08195 - Sant Cugat del Vallès (Barcelona) 
Spain 
E-mail: mgiralt@uic.es 

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Abstract: 
Aim: To study the correlation between PAV (pharyngeal airway volume), the 
clinical indicators of OSA (obstructive sleep apnea) and the impact of 
orthognathic surgery on them. 
 
METHODS: A prospective, descriptive, unicentric three-arm study carried out by 
a multidisciplinary team to evaluate the following parameters in patients receiving 
orthognathic surgery during the study period: 
o First arm: patients with OSA treated in terms of bimaxillary 
orthognathic surgery 
o Second arm: patients with OSA treated in terms by Maxillary surgery 
solely. 
o Third arm: patients with OSA treated in terms of mandibular surgery 
solely. 
Key Words: Orthognathic surgery; Three- dimensional analysis; Upper Airway; 
cone-beam; Obstructive Sleep Apnea Syndrome; Obstructive Sleep Apnea. 

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I. 
Introduction 
Sleep apnea-hypopnea syndrome (OSA) is estimated to affect 5-20% of the 
general Spanish adult population, although a study by Duran et al. 1 reports 
figures of up to 26%, and it is 2-3 times more common in men than in women 1. 
In addition, statistics show that more than 50% of affections are not and will not 
be diagnosed. In Spain, according to studies carried out in different age 
subgroups, it is estimated that there are between 5 and 7 million people who 
suffer from sleep apnea 1,2. 
It is dyssomnia with respiratory pauses secondary to partial (hypopnea) or 
complete (apnea) obstruction of the upper airway (UA) 3. 
The upper airway is occluded due to a drop in muscle tone of the upper airway 
dilator muscles during sleep, leading to partial narrowing or complete obstruction. 
The direct consequences of these episodes are the repetitive decrease in blood 
oxygen saturation and transient and recurrent awakenings from sleep caused by 
increased respiratory effort, which causes a reduction in the quality of sleep 3. 
When all these disorders They are also accompanied by clinical manifestations, 
such as excessive daytime sleepiness (EDS), neuropsychiatric, metabolic, 
respiratory and cardiac alterations, we classify it as OSA 3,4. 
Recent studies suggest that patients with undiagnosed OSA consume between 
2-3 times more resources than the general population 1,2. Most of the costs are 
attributable to more days of hospital stay, more consultations in specialized care 
and an increase in the pharmacological treatment prescribed 2. 
The diagnosis of OSA requires the recording of multiple physiological signals 
during sleep 1-3. The reference diagnostic test, considered as the standard 
pattern for the detection of OSA, is polysomnography (PSG) 1-8. This consists of 
recording brain activity, breathing, heart rate, muscle activity, snoring and blood 
oxygen levels while sleeping. It is a test indicated for different sleep disorders 
such as OSA; and it is done at night. Thus, PSG records repeated episodes of 
upper airway obstruction during sleep, and these episodes are measured with 
the apnea-hypopnea index (AHI) 1-8. An AHI greater than 5 per hour associated 
with symptoms not explained by another cause would lead to the diagnosis of the 
disease 1-4. 

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Currently, the standard treatment of patients with OSA is by means of a CPAP 
(continuous positive airway pressure) device, which has limited degrees of 
compliance and tolerance (less than 50%), due to the discomfort of the device 
1,3 ,5-8. 
However, advancement surgery of the maxillary-mandibular complex has shown 
a success rate of 86% 5-9,12-19. Several studies have also been carried out that 
support that advancement surgery of the maxillary-mandibular complex 
increases the volume of the upper airway through direct imaging with endoscopy 
or 3D imaging studies with CBCT (Cone Beam Computed Tomography), CT 
(Computed Tomography) or MRN (Magnetic Resonance) 20-22. These surgical 
procedures were previously considered aggressive techniques with long and 
heavy postoperative periods, but today, with the appearance of virtual planning 
protocols and minimally invasive surgical techniques, the surgical time for these 
procedures is around two hours, they are performed generally in a 24-h 
hospitalization regimen and the postoperative ones are very well tolerated by the 
vast majority of patients 20-22 . 
Despite this, to date there are no published studies that relate the impact of the 
replacement surgery of each one of the jaws in the three dimensions of space 
and the 3D volumetric changes of the UA obtained with it, on the AHI and other 
indicators. clinics of patients with SAHS. For this reason, the objective of this 
project is to correlate each of the movements of the maxillomandibular complex 
in the three axes of space performed during orthognathic surgery, with the 
volume of the UA, the AHI and the clinical indicators of OSA. 
 
II. 
Objectives 
 
OBJECTIVES: To study the correlation between pharyngeal airway volume 
(PAV), the clinical indicators of obstructive sleep apnea (AHI, ESS), and the 
impact of orthognathic surgery on them. 
 
During the study period: 
 
• Record of the type, magnitude and direction of surgical movements of the 
maxillofacial complex made during the surgery (Day 0-Month 1). 
• Assessment of PAS/PAV stability (relapse) at short term (1 month). 

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3D PAV assessment by cranial voxel-based superimposition protocol 
before and one month and 12 months after orthognathic surgery. 
 
• Household polysomnography (PSG) registry/ apnea-hypopnea index (Day 
0, Month 1 and Month 12). (AHI evaluation bu neurophysiologist) 
• Assessment of the clinical indicators of obstructive sleep apnea at day 0, 
month 1 and month 12:, blood pressure (mm Hg) , and daytime 
hypersomnia test (Epworth sleepiness scale, ESS) (Day 0, Month 1 and 
Month 12). 
• Record of body mass index (BMI) (cm/Kg2) 
 
Main Objective: 
 
• Evaluate the impact of orthognathic surgery (bimaxillary or monomaxillary) 
and its movements on the PAV and the clinical indicators of OSA. 
 
Specific objectives: 
 
• 
Interrelate the degree of dentofacial deformity with the IAH. 
 
• Study the potential correlation between the volume of the VAS and the 
IAH. 
• Correlate the type, direction and magnitude of the surgical movements of 
the maxillofacial complex with PAV/PAS increase Correlate the type, 
direction and magnitude of the surgical movements of the maxillofacial 
complex with the cure of OSA (household PSG AHI assessment) and the 
following clinical indicators of OSA: diurnal hypersomnia test (ESD, ESS). 
• Evaluate negative effects of either maxillary or mandibular surgical 
movements in PAS/PAV increase and the cures of OSA. 
• Evaluate negative effects of either maxillary or mandibular surgical 
movements in the improvement of the clinical symptoms and the cure of 
OSA. 
• To study the possible effect of surgical complications on PAS/PAV stability 
at long term and the clinical symptoms of OSA. 
• Demonstrate that maxillomandibular surgery is a defined, predictable and 
a definitive cure for OSA. 
• Demonstrate that skeletal, linear, and cross-sectional volume parameters 
remain stable at long-term. 
• Demonstrate that AHI and OSA-related parameters stay stable at long 
term after mono- or bimaxillary surgery. 

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Hypothesis 
 
• H1a: Maxillomandibular advancement (orthognathic surgery) does 
correlate with the volume of the upper airway, at both short or long term. 
• H2a: Maxillomandibular advancement (orthognathic surgery) does 
correlate with the clinical indicators of obstructive sleep apnea, at both 
short or long term. 
 
Material and methods 
 
METHODS: A prospective, descriptive, unicentric study carried out by a 
multidisciplinary team to evaluate the following parameters in patients 
undergoing orthognathic surgery at Maxillofacial institute Teknon medical 
center. 
 
Study design: 
A prospective single-center intervention study will be carried out by a 
multidisciplinary team made up of oral and maxillofacial surgeons, 
neurophysiologists, anesthesiologists and nurses, at the Maxillofacial Institute of 
the Teknon Barcelona Medical Center, together with the Department of Oral and 
Maxillofacial Surgery of the International University of Catalonia. 
o First arm: patients with OSA treated in terms of bimaxillary 
orthognathic surgery 
o Second arm: patients with OSA treated in terms by Maxillary surgery 
solely. 
o Third arm: patients with OSA treated in terms of mandibular surgery 
solely. 
 

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This research protocol has been accepted by the Ethics Committee (CEIC) of the 
Maxillofacial Institute of the Teknon Medical Center (Barcelona, Spain) (ANNEX 
V) and by the CEIC of the International University of Catalonia (Sant Cugat del 
Vallès, Barcelona, Spain). All enrolled subjects will receive detailed study 
information and will be offered to sign informed consent prior to the start of the 
study. 
 
Reference population: 
A total of 80 patients, over 18 years of age, surgically treated for dentofacial 
deformities by orthognathic surgery at the Maxillofacial Institute of the Teknon 
Medical Center, Barcelona, will be included in the study. 
 
All subjects included in the study will undergo home portable PSG which will be 
evaluated by a specialist in neurophysiology. Portable devices have proven to be 
an acceptable alternative method for diagnosis in subjects with a high pretest 
probability of at least moderate or severe OSA, and who do not have 
cardiopulmonary impairment. In the event of upper airway obstruction, they will 
be evaluated together with the otorhinolaryngology service of the Teknon Medical 
Center, Barcelona. 
 
Sample size: 
It has been decided to include a sample of 80 patients in order to obtain 
statistically significant results. This sample size will allow us to complete the 
recruitment in 18 months. 
To be included in the study, patients must meet the following criteria: 
Inclusion Criteria: 
1. Patients over 18 years of age who present any kind of dentofacial 
deformity candidates for orthognathic surgery 
treatment. 
2. Growth of the maxillofacial complex completed. 
3. Patients without uncontrolled cardio-pulmonary disease. 
4. Patients willing to understand the procedures of the study and that agree 
to give their signed informed consent. 
5. Patients who commit to perform the postoperative controls for at least 
one postoperative year. 
6. Patients with a good general condition of health, confirmed by pre- 
operative study and assessment by Anaesthesiology 
(ASA). 

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Exclusion Criteria: 
1. Patients with a clinical history in which any surgery would be 
contraindicated 
2. Patients with any facial Syndromic malformation 
3. Patients who have undergone chemotherapy or radiotherapy during the 
last 5 years, including area of head and neck. 
4. Patients who refuse to accept the clinical conditions of the study and are 
not willing to sign the form corresponding 
informed consent. 
5. Patients who are expected to lack adherence to follow-up or to 
 
Surgical Procedure 
 
o Patients who meet the eligibility criteria and have given consent for 
inclusion in the study will be entered into the center's surgical 
protocol. 
o Treatment: Mono or Bimaxillary Orthognathic Surgery. The jaw 
replacement surgery is carried out under general anesthesia using 
minimally invasive techniques, the patient is extubated after surgery, 
antibiotics, anti-inflammatories, and antiemetics are prescribed during 
admission and a closed circuit local cold mask is applied at 17ºC. The 
patient is discharged after 24 h. 
• 
First arm: patients with OSA treated in terms of bimaxillary 
orthognathic surgery 
• 
Second arm: patients with OSA treated in terms by Maxillary 
surgery solely. 
• 
Third arm: patients with OSA treated in terms of mandibular 
surgery solely. 
 
Workplan 
Initial Visit (T0): 
• Preoperative visit (T0) 1 week before surgery performed by the 
nursing team and staff: 

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o Explain the study and the procedure to be carried out, giving 
an information document to the patient and proceeding to sign 
the informed consent. 
o Collection of demographic and clinical variables of interest. 
o Record-taking according to the center's treatment protocol for 
case study and surgical planning: CBCT, intraoral scanning, 
photos, occlusal records. (Hernández-Alfaro PROTOCOL 
2013) 24. 
o Explanation of the treatment plan and surgery schedule. 
o Assessment of BP**(blood preasure), BMI and Epworth 
Test(1). 
• 
** BP is recorded on two occasions with a time interval 
of 5 minutes under the same conditions. 
o Delivery and placement of the home PSG(1) device. 
 
Follow-up visits (T1-T2): 
• 
Visits carried out by the same team of surgeons who performed the 
initial visit and the intervention. Patients will be evaluated one 
month (T1) and 12 months (T2) after surgery. In each of these visits, 
the patient will be questioned and explored, with the aim of 
evaluating the post-surgical evolution and the possible appearance 
of early and late complications typical of the intervention. Apart from 
the clinical control, a photographic record, CBCT, BP**, BMI, 
Epworth test and PSG will also be carried out. 

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** on two occasions with a time interval of 5 minutes, blood 
pressure is recorded under the same conditions 
 
 
Data collection: Radiological assessment. 
 
 
It will be performed using cone beam computed tomography (CBCT). Two 
investigators with a high level of experience with 3D virtual image overlay 
techniques, using the Dolphin software (Dolphin Imaging 11.9 Premium, 
Chatsowrth, CA, USA), will assess the volume changes of the upper airway 
(naso-, gold - and hypo-pharynx) (Fig. 13), and the stability of the surgery in the 
long term (it is verified that there is no recurrence of the movements carried out 
during surgery). To ensure the precision of the measurements, fixed points at the 
base of the skull are taken as reference. 
 
A CBCT will be performed at baseline, as well as one month and twelve months 
post-treatment. 
 
The images of the three CBCTs of each patient are stored in iCat Vision, which 
are exported to the Dolphin software (Dolphin Imaging 11.9 Premium, 
Chatsowrth, CA, USA), in DICOM format with which the necessary 
measurements are carried out. to accurately quantify the movements produced 
in the jaws and the volume of the UA. 

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Outcome measurements: 
• Main variable: Evaluation of the volume change of the upper airway and 
the amount and direction of movement of both jaws during jaw 
replacement surgery, comparing the measurements of the CBCT before 
(T0) and one month (T1) and 1 year (T2) of the jaw surgery. 
 
• Secondary variables: 
 
o Evaluation of the increase in volume of the upper airway by means 
of CBCT one month and one year after jaw replacement surgery. 
o Evaluation of the clinical indicators of OSA by taking a BP, and 
daytime hypersomnia test (Epworth Test) one month and one year 
after jaw replacement surgery. The BMI is calculated to detect 
those changes in the AHI due to weight changes. 
o Presence of early or late surgical complications 
o Study of the stability of surgical movements of the jaws one month 
and one year after surgery by superimposing CBCT images. 
 
Statistical analysis. 
The descriptive analysis will include the most relevant statistics for each of 
the linear, angular and volumetric parameters, as well as patient profile variables 
and intervention characteristics: mean, standard deviation, minimum, maximum 
and median for the continuous and absolute frequencies and percentages for the 
categorical. 
Using a Kolmogorov-Smirnov test, the adjustment to normal distribution of 
the different dimensions will be verified. Given the sample size, the objectives will 
be addressed from a parametric analysis approach. 
The inferential analysis will include the following statistical methods: 
For each group: 
o ANOVA general linear model of repeated measures, to compare the 
evolution of the skeletal and volumetric parameters of the pathway 
throughout the follow-up. The multiple comparisons will be made with the 

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Bonferroni correction and will allow assessing the effects in the short term 
(T1-T0), stability (T2-T1) and long term (T2-T0). 
o Pearson's linear correlation coefficient, to estimate the degree of 
association between volumetric and skeletal changes, also in the different 
periods (T0, T1 and T2). 
o Independent samples t tests, Mann-Whitney and Kruskal-Wallis non- 
parametric tests to assess differences in volumetric changes according to 
aspects of the individual's profile and type of surgery. 
o The level of significance used in the analyzes will be 5%. 
 
Ethical Considerations. 
The guidelines of the Declaration of Helsinki will be followed in all phases of 
treatment and written informed consent will be obtained from all subjects. 
 
Referencias. 
 
 
1. Duran J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea 
hipopnea and related clinical features in a population- based sample of 
subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001;163:685-689. 
2. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The 
occurrence of sleep disorder breathing among middle aged adults. N Engl 
J Med 1993; 328:1230– 1235. 
3. American Academy of Sleep Medicine. International Classification of 
Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, Ill: 
American . Academy of Sleep Medicine; 2005. 
4. Johns MW. A new method for measuring daytime sleepiness: the 
Epworth Sleepiness Scale. Sleep 1991;14:540-545. 
5. Camacho M, Certal V, Capasso R. Comprehensive review of surgeries 
for obstructive sleep apnea syndrome. Braz J Otorhinolaryngol. 
2013;79(6):780-8. 
6. Gungor A. Advanced airway management strategies for severe OSAS 
and craniofacial anomalies. Am J Otolaryngol. 2017;38(1):77-81. 

14 
OSAS-OS Protocol v1.0 October 30, 2017 – Confidential 
7. Torres HM, Valladares-Neto J, Torres ÉM, Freitas RZ, Silva MA. Effect 
of 
Genioplasty 
on 
the 
Pharyngeal 
Airway 
Space 
Following 
Maxillomandibular Advancement Surgery. J Oral Maxillofac Surg. 
2017;75(1):189.e1-189.e12. 
8. Andrews, B. T., & Urata, M. M. (2016). Surgical Management of 
Obstructive Sleep Apnea, 1263–1272. 
9. Hernández-Alfaro F, Guijarro-Martínez R, Mareque-Bueno J. Effect of 
Mono- and Bimaxillary Advancement on Pharyngeal Airway Volume- 
Cone-Beam Computed Tomography Evaluation. J Oral Maxillofac Surg. 
2011;69(11):e395-400. 
10. Vigneron A, Tamisier R, Orset E, Pepin JL, Bettega G. 
Maxillomandibular advancement for obstructive sleep apnea syndrome. J 
Craniomaxillofac Surg. 2016. pii: S1010-5182(16)30309-2. 
11. Ronchi P, Cinquini V, Ambrosoli A, Caprioglio A. Maxillomandibular 
advancement in obstructive sleep apnea syndrome patients: a 
restrospective study on the sagittal cephalometric variables. J Oral 
Maxillofac Res. 2013;4(2):e5. 
12. Hatab NA, Konstantinović VS, Mudrak JK. Pharyngeal airway changes 
after mono- and bimaxillary surgery in skeletal class III patients- Cone- 
beam computed tomography evaluation. J Craniomaxillofac Surg. 
2015;43(4):491-6. 
13. Rosário, H. D., Oliveira, G. M. S., Freires, I. A., de Souza Matos, F., & 
Paranhos, L. R. (2016). Efficiency of bimaxillary advancement surgery in 
increasing the volume of the upper airways: a systematic review of 
observational studies and meta-analysis. European Archives of Oto- 
Rhino-Laryngology, 1–10. 
14. Zaghi, S., Holty, J.-E. C., Certal, V., Abdullatif, J., Guilleminault, C., 
Powell, N. B., Camacho, M. (2015). Maxillomandibular Advancement for 
Treatment of Obstructive Sleep Apnea: A Meta-analysis. JAMA 
Otolaryngology-- Head & Neck Surgery, 90095(1), 1–9. 
15. Choi, J. W., Park, Y. J., & Lee, C.-Y. (2015). Posterior Pharyngeal 
Airway in Clockwise Rotation of Maxillomandibular Complex Using 

15 
OSAS-OS Protocol v1.0 October 30, 2017 – Confidential 
Surgery-first Orthognathic Approach. Plastic and Reconstructive Surgery. 
Global Open, 3(8), e485. 
16. Santagata, M., Tozzi, U., Lamart, E., & Tartaro, G. (2014). Effect of 
orthognathic surgery on the posterior airway space in patients affected by 
skeletal class III malocclusion. Journal of Oral and Maxillofacial Surgery, 
14(3), 682–686. 
17. Ubaldo, E. D., Greenlee, G. M., Moore, J., Sommers, E., & Bollen, A. 
M. (2015). Cephalometric analysis and long-term outcomes of 
orthognathic surgical treatment for obstructive sleep apnoea. International 
Journal of Oral and Maxillofacial Surgery, 44(6), 752–759. 
18. Lee, S. H., Kaban, L. B., & Lahey, E. T. (2015). Skeletal stability of 
patients undergoing maxillomandibular advancement for treatment of 
obstructive sleep apnea. Journal of Oral and Maxillofacial Surgery, 73(4), 
694–700. 
19. Raffaini M, Pisani C (2013) Clinical and cone-beam computed 
tomography evaluation of the three-dimensional increase in pharyngeal 
airway space following maxillo-mandibular rotation- advancement for 
class II-correction in patients without sleep apnoea (OSA). J 
Craniomaxillofac Surg 41:552–557. 
20. Guijarro-Martínez R, Swennen GR. Three-dimensional cone beam 
computed tomography definition of the anatomical subregions of the upper 
airway- a validation study. Int J Oral Maxillofac Surg. 2013;42(9):1140-9. 
21. Peiró-Guijarro MA, Guijarro-Martínez R, Hernández-Alfaro F. Surgery 
first in orthognathic surgery: A systematic review of the literature. Am J 
Orthod Dentofacial Orthop. 2016;149(4):448-62. 
22. Aboul-Hosn Centenero S, Hernández-Alfaro F. 3D planning in 
orthognathic surgery: CAD/CAM surgical splints and prediction of the soft 
and hard tissues results - our experience in 16 cases. J Craniomaxillofac 
Surg. 2012;40(2):162-8. 
23. Shrestha BM. The Declaration of Helsinki in relation to Medical 
Research: Historical and Current Perspectives. J Nepal Health Res 
Counc. 2012;10(22):113-7. 

16 
OSAS-OS Protocol v1.0 October 30, 2017 – Confidential 
24. Hernández-Alfaro F, Guijarro-Martínez R: New protocol for three- 
dimensional surgical planning and CAD/CAM splint generation in 
orthognathic surgery: An in vitro and in vivo study. Int J Oral Maxillofac 
Surg, 2013.