## 2 Materials and Methods  
The sample size calculation (G*Power version 3.1.9.2, [PERSON], Universitat Kiel, Germany) revealed that to be able to detect a moderate effect size of 0.5 with a probability of 0.05 and a power of 0.9, 44 subjects were needed. Therefore, 50 consecutive subjects (26 men and 24 women; mean age of \(48.5\pm 8.7\) years) with a diagnosis of OSA were retrospectively enrolled in the present study among the patients treated at the Department of Orthodontics, University of Foggia, Italy, in chronological order from January 2016 to February 2019. To be included in the study, the patients had to fulfil the following inclusion criteria: age greater than 20 years old, body mass index (BMI) lower than 34 kg/m\({}^{2}\), OSA diagnosis confirmed by nocturnal polysomnography, treatment with night-time MAD therapy using a fully customizable device after a drug-induced sleep endoscopy (DISE) and completeness of diagnostic records. Exclusion criteria were a smoking habit, the presence of comorbidities like cardiovascular or pulmonary diseases at the moment of the OSA diagnosis, taking concomitant medications for neurological disorders or a history of cervical head trauma.  
All the procedures described in the present research protocol adhered to the Declaration of Helsinki (1975) (and the subsequent revisions) and were approved by the Ethical Committee of the University of Foggia (Approval no. 43/CE/2019) and all patients gave their informed consent to participate.  
MAD treatment was always initiated after performing a DISE. Every patient, before MAD treatment (T0), received split-night polysomnography (SN-PSG) with at least 4 h of continuous recording in a sleep laboratory using a type 2 portable device (Embleta system X-100, Flaga, Reykjavik, Iceland) after one night of adaptation to the hospital setting. The SN-PSG recording comprehended electroencephalograms, electro-oculograms, electromyograms, pulse oximetry channels, abdominal respiratory effort bands, body position sensors, nasal cannulas and oral thermistor. The first 3 h of recording, as recommended by several authors [25; 26; 27; 28], were used for manual scoring according to the AASM criteria from 2007 [29].  
The following parameters were recorded and stored for further analysis: apnea/hypopnea index (AHI); oxygen desaturation index (ODI), which corresponds to the number of desaturation events higher than 4% of the baseline value per hour of sleep; and the average HR, minimum HR and maximum HR.  
A second SN-PSG was performed after 3 months of treatment (T1) with a fully customizable MAD (Prottrusor(r), nonrusso+(r), Dr [PERSON], Belluno, Italy). The MAD (Figure 1) was made of two resin splints joined by two threaded titanium bars with two titanium screws each, which represents the protrusive mechanism. The head of the titanium screws allows for lateral excursion of the mandible for improved patient comfort. The amount of mandibular advancement was determined for each patient after a titration period. Initially, an intraoral gauge (Occlusion(r), nonrusso-r), Dr [PERSON], Belluno, Italy) was used to set the advancement at 70% of the total possible mandibular advancement; then, during follow-up appointments, usually every 15 days, the therapeutic mandibular protrusion was adjusted by 1 mm or 2 mm increments until reaching the most comfortable position that allowed relief from the symptoms, as described in a previous study [30].