Diaferia 2017.

Study characteristics
Methods	Study design: parallel, RCT. Recruitment period: not specified. Duration of study: study start date: October 2010. Actual primary completion date: December 2011. Study setting: outpatient. Universidade Federal de São Paulo, São Paulo, Brazil.
Participants	Key inclusion criteria: men, age 25 to 65 years, BMI lower than 35 kg/m2, and with OSA diagnosis confirmed by clinical and polysomnographic criteria. Key exclusion criteria: women; participants who were uncooperative, illiterate, or who had a low education level that prevented the completion of questionnaires and the understanding of the guidelines about the use of CPAP and practice of exercises that have been written to be practiced at home; patients with other sleep disorders or with previous treatment for OSA (i.e., CPAP, intraoral device, or surgery); patients with serious or decompensated clinical or psychiatric medical illnesses, such as congestive heart failure, cardiomyopathy, COPD, chronic active hepatitis, liver cirrhosis with severe symptoms, myasthenia gravis, demyelinating disease, motor neuron disease, depression, schizophrenia, obsessive compulsive disorder, disorder anxiety, bipolar disorder, eating disorder, attention deficit disorder, and hyperactivity; patients who used alcohol, stimulants or sedatives; and patients with grade III or IV palatine tonsils, grade II or III septal deviation, or evident micrognathia. Gender: all men. Age: mean (SD): participants that completed the study: 48.1 (11.2) years old. Participants that did not complete the study: 39.4 (10.1). BMI: mean (SD): participants that completed the study: 27.4 (4.9) kg/m2. Participants that did not complete the study: 28.1 (3.0) kg/m2. AHI (events/hour): mean (SD) in participants that completed the study: 30.9 (20.6). Participants that did not complete the study: 30.4 (20.2). ESS: mean (SD): participants that completed the study: 12.7 (3.0). Participants that did not complete the study: 12.1 (1.8). N randomised: 140 participants: 35 placebo, 35 myofunctional therapy, 35 CPAP, and 35 combined therapy. N analysed: 100. Dropouts: 40 participants: 11 in placebo group for "reported worsening of OSA and snoring"; 8 in myofunctional therapy group “quit speech therapy exercises”; 8 in CPAP group “quit use of CPAP”; and 13 in combined therapy group “performed exercises but did not use CPAP”.
Interventions	Intervention: oropharyngeal exercises. The participants were instructed by one speech pathologist to perform the following tasks: Soft palate: elevation of the soft palate and uvula while pronouncing an oral vowel intermittently /a/ (isotonic exercise) and continuously (isometric exercise). The palatopharyngeal, palatoglossus, uvula, tensor veli palatini, and levator veli palatini muscle are recruited in this exercise. The isotonic exercise also recruits pharyngeus lateral wall. These exercises had to be repeated daily, three times a day, for 3 minutes and were performed once a week under supervision to ensure adequate effort. Tongue: brushing the superior and lateral surfaces of the tongue while the tongue is positioned in the floor of the mouth (5 times each movement, 3 times a day); pushing the tip of the tongue against the hard palate and sliding the tongue backward (20 times, 3 times a day); sucking the tongue upward against the palate, pressing the entire tongue against the palate (20 times); and rotating the tongue in the oral vestibule 10 times right and left side. Forcing the back of the tongue against the floor of the mouth while keeping the tip of the tongue in contact with the inferior incisive teeth (20 times, 3 times a day). Stomatognathic functions: Suction: sucking yogurt with a narrow straw. Breathing and speech: forced nasal inspiration and oral expiration in conjunction with phonation of open vowels, while sitting; and balloon inflation with prolonged nasal inspiration and then forced blowing, repeated 5 times without taking the balloon out of the mouth. Swallowing and chewing: alternate bilateral chewing and deglutition, using the tongue in the palate, closed teeth, without perioral contraction, whenever feeding. This exercise aims for the correct position of the tongue while eating and targets the appropriate functionality and movement of the tongue and jaw. The patients were instructed to incorporate this mastication pattern whenever they were eating. Comparators: Placebo. The patients were instructed by one speech pathologist to perform exercises without therapeutic function (relaxation and stretching of the neck muscles). CPAP. All participants from the CPAP and combined groups underwent a full night, attended PSG to manually determine the optimum pressure of CPAP. The CPAP titration was performed according to the protocol proposed by the American Academy of Sleep Medicine. Combined therapy: CPAP plus oropharyngeal exercises. Placebo exercises and oropharyngeal exercises were performed at home for 3 months with 3 daily exercise sessions of 20 minutes each. Concomitant interventions: None.
Outcomes	Prespecified outcomes Primary Outcome Measures: Objective sleep pattern: sleep stages, arousals, apnoea‐hypopnoea index, oxyhaemoglobin saturation evaluated by polysomnography. Secondary Outcome Measures: Daytime sleepiness (ESS). Quality of life (WHOQOL‐BREF and FOSQ questionnaires). Cognition. Evaluations of psychomotor vigilance test. Time points of measurement: before treatment and 90 days after and 3 weeks later (“washout”) for all outcomes. Reported outcomes: Results on quality of life, cognition and psychomotor vigilance test were not reported.
Notes	Quote in NCT01289405: “target number of participants that the researchers need for the study: 80”. But 140 participants were included. No information provided on reasons for the increase in final participants. Additional information on allocation procedures requested from authors, but no answer received. Funding for trial: Associação Fundo de Incentivo à Pesquisa—AFIP Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Conflicts of interest: the authors declare that they have no conflict of interest. Registered: ClinicalTrials.gov NCT01289405. Sample size calculations: quote: “The G*Power 3.1.10 program was used to calculate sample sizes. With an expected difference in the hours of CPAP used between the CPAP group and the combined group (0.40), α of 0.05 and sample size of 54 patients (27 patients in CPAP and 27 combined group), a power of 0.85 was found. The significance level was set at 5%." Data sharing statement: none.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Prior to treatment, the patients were divided randomly into four groups". Comment: no description of the randomisation process.
Allocation concealment (selection bias)	Unclear risk	Not reported. Method of allocation concealment not mentioned.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote in NCT01289405: "Double blinding (Participant, Investigator)".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote in NCT01289405: "Double blinding (Participant, Investigator)".
Incomplete outcome data (attrition bias) All outcomes	High risk	Figure 2. The flow chart of patient selection during this study started with 140 participants, 35 randomised to each of the four groups. Dropouts: 11 in placebo group for “reported worsening of OSA and snoring”; 8 in myofunctional therapy group “quit speech therapy exercises”; 8 in CPAP group “quit use of CPAP”; and 13 in combined therapy group “performed exercises but did not use CPAP”. 140 patients with 40 patients failing to complete the study. However, differences in dropout rates are not statistically significant.
Selective reporting (reporting bias)	Low risk	Prespecified relevant outcomes in clinicaltrials.gov were reported.
Other bias	Low risk	The study appears to be free of other sources of bias.