Introduction 1 2 3 4 5 6 7 12 13 14 15 17 14 The primary goal of this study was to use a self-applied limited channel recorder to objectively assess the effectiveness of MAD therapy when the dentist determined the patient had reached the titration endpoint. A second goal was to determine factors which might predict successful treatment outcomes and provide a more refined method for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Finally, we wanted to demonstrate two potential models of collaboration between the dentist and sleep medicine physician in monitoring MAD treatment outcomes. Materials and methods Eleven females and 19 males were recruited from two dental practices before treatment with an oral appliance and enrolled in the study. Twenty-five of the patients had failed CPAP therapy. After obtaining an informed consent (approved by the BioMed IRB, San Diego, CA, USA) patients completed a two-night pretreatment in-home study with the Apnea Risk Evaluation System (ARES TM) Unicorder  TM (Advanced Brain Monitoring, Carlsbad, CA, USA). This pretreatment recording was conducted between the time the dental impressions were taken and when the TAP II Mandibular Advancement Device (MAD) (Airway Management, Dallas, TX, USA) was fabricated and ready for insertion. The TAP is a custom-made oral appliance with separate upper and lower appliances joined by a titration or advancement mechanism on the upper and a transverse bar or socket on the lower. The titration mechanism uses a hook to engage the bar or socket on the lower once each device is placed in the mouth. A jackscrew controls the position of the hook and thus the amount of protrusion. The patient can self-titrate the device using a removable hex key which engages the screw. On the day of insertion of the MAD, patients completed the Beck depression index, Epworth sleepiness scale, and the Flemons’ quality of life questionnaire. At the insertion appointment, both study sites attempted to achieve a starting MAD titration position whereby the patient could just hook the lower tray with the upper tray using active protrusion with both trays in place. In the rare occasion that this level of advancement was not tolerated by the patient, the starting protrusion was reduced. Patients were instructed to begin adjusting the MAD in one-half turn increments as soon as it was tolerable, until a cessation in snoring or the symptoms had resolved. As a result, the titration endpoint was determined by the dentist based on the patient’s self-report. At the follow-up appointment, which was typically scheduled 3 to 4 weeks subsequent to the MAD insertion, the assessment questionnaires were completed again and the ARES Unicorder study was repeated. Twenty-seven of the 30 patients reached their endpoint within 34 days. The other three patients completed their endpoint in 40, 61, and 75 days; the delay in reaching the endpoint was due to patient illness unrelated to this study. In between the time that treatment was initiated and the titration endpoint, each patient maintained a daily journal that recorded the time the appliance was inserted each night, and the time it was removed in the morning. 18 1 Fig. 1 Patient wearing a unicorder  18 19 Automated scoring algorithms were applied off-line to detect sleep disordered breathing. The AHI was computed using a time-in-bed measure based on recording time with acceptable signal quality minus periods when the patient was upright or presumed to be awake based on actigraphy. Apneas, based on a 10-s cessation of airflow detected by the automated algorithms, were included in all apnea–hypopnea indexes (AHI). Hypopnea events required a 50% reduction and recovery in airflow and were further stratified based on the depth of desaturation. The AHI-4% criteria required a minimum 3.5% reduction in SpO2 and at least a 1.0% recovery. Hypopneas included in the AHI-3% and AHI-1% criteria required SpO2 desaturation and resaturation using stepped thresholds. For the AHI-3%, if the SpO2 at the point of maximum saturation before the event was greater than or equal to 95% then a 2.2% reduction and a 2.2% recovery in SpO2 was required. For maximum saturations of between 95–93% the required SpO2 change was a 2.5% reduction and 2.5% recovery; between 93–91% a 3.0% reduction and 2.7% recovery; between 91–88% a 3.5% reduction and 3.0% recovery; and below 88% a 4.0% reduction and 3.5% recovery. For the AHI-1%, if the point of maximum saturation before the event was greater than 93%, then a 1.0% reduction and 1.0% recovery was required; and for events with a starting SpO2 between 93–91%, a 1.2% reduction and 1.2% recovery was required. For an AHI-1% event to be called, the change in flow and desaturation needed to be associated with a behavioral arousal (i.e., an abrupt change in pulse rate, snoring sound or a head movement). After the automated scoring was applied, the full disclosure recordings were visually inspected by a sleep medicine physician to confirm the accuracy of the automated scoring, and to reclassify as central and/or exclude autodetected events if necessary. At the time of the review, the clinician was blinded to the study status (i.e., pre- or posttreatment). The physiological data, including AHI values, percent time with SpO2 below 90, 85, and 80%, and percentage time snoring greater than 30, 40, 50, and 60 dB were then calculated. 20 21 t n n t To develop and validate the prediction of the posttreatment AHI using pretreatment data, patients were paired and assigned into either the model development or cross validation group based on similarities in the pre- and post-4% AHI and 1% AHI. Correlation analysis was used to identify anthropomorphic variables and measures of obstructive breathing before treatment which might be useful in estimating the posttreatment 4% AHI (post-T 4%). Variables with significant correlations were then used in a linear regression to derive predicted posttreatment values (predict AHI). Results Overall effects of MAD treatment t p 2 Fig. 2 Mean + SE changes in pre- and posttreatment AHI-4% and AHI-1%  p p 3 Fig. 3 Mean + SE changes in pre- and posttreatment percentage of time the SpO2 was <90%, and the percentage change in SpO2 resulting from sleep disordered breathing  p 4 Fig. 4 Mean + SE changes in pre- and posttreatment snoring loudness above 30 and 40 dB  5 Fig. 5 a b  5 t p 6 Fig. 6 Pre- and posttreatment changes in Beck depression index, Epworth sleepiness scale, and Flemons’ quality of life index  7 Fig. 7 Regression plot predicting posttreatment AHI-4% based on the posttreatment percentage of time the snoring loudness was above 30 dB  Factors that affect treatment outcomes 1 p p p Table 1 Characteristics of group that was treated optimally and the group that was not treated optionally with a MAD (mean + SE)   Treated optimally post-T AHI-4% < 5 Did not treat optimally post-T AHI-4% > 5 Gender Females 7 4 Males 11 8 Age (years) 48.3 + 2.5 50.9 + 3.4 BMI (kg/m)** 27.6 + 0.8 33.1 + 2.1 Weight (kg)** 84.4 + 3.0 100.2 + 5.0 Neck circumference (cm)* 40.0 + 0.7 43.2 + 1.0 p p Prediction of successful treatment outcome n 2 Table 2 Correlations between posttreatment AHI-4% and pretreatment measures r p r p Pretreatment 4% AHI r Snoring >30 dB r Pretreatment 3% AHI r Neck circumference r Pretreatment 1% AHI r Body mass index r Snoring >40 dB r Weight r % Time <90% SpO2 r   R 2 8 9 Fig. 8 a b  Fig. 9 a b  Discussion Consecutive patients who were referred to the dentist for a MAD were provided the opportunity to enroll in the study. The only exclusion criteria applied were ages less than 18 or older than 70 years. The inclusion of 25 subjects who had previously failed CPAP therapy contributed to the wide OSA severity range: nine of the subjects (30%) were considered to have severe OSA (i.e., AHI-4% ≥ 30) and an additional 30% were considered to have moderate OSA (AHI-4%>15 and <30). Seventy-seven percent of the patients (23/30) had at AHI-1%>25, a clinical cut-off which was considered at least moderate. In this study, a treatment efficacy rate for the MAD was 90% using an AHI-4% clinical cut-off of 10, and 97% when a 50% reduction in AHI was included in determining a successful outcome. Eighty-seven percent of the patients showed improvement using an AHI-1% with a clinical cut-off of 15 or a 50% reduction in AHI. Eighty percent of the patients (24/30) had a posttreatment AHI-1% ≤ 16. 14 In an attempt to compare these previous finding to this data set, a clinical cut-off of 10 was applied to the AHI-1%. The differences between the AHI-1% and RDI include a 50% reduction in flow vs 30%; a 1% desaturation vs no desaturation; arousal indicators based on changes in snoring, pulse rate, and head movement vs cortical arousals; and the use of time-in-bed vs total-sleep-time. Using this alternative clinical cut-off, 33% of the patients had a successful outcome. When a 50% reduction in AHI-1% was included, 77% had a successful outcome. Results are more consistent with the previous research. 14 22 25 r 7 26 27 28 14 . 27 28 The successful treatment outcome of patients with severe sleep apnea suggests that a more quantitative approach should be investigated to identify candidates appropriate for a MAD therapy. The results from the predictive model, once fully validated, could provide the guidance needed for sleep medicine physicians to recommend an oral appliance as an initial treatment option for more severe patients. Alternatively, substantial differences between the predicted and actual posttreatment AHI could help dentists determine when a patient has not been fully titrated. n 2 29 A follow-up PSG is generally not affordable in cases where it is not covered by an insurance company or health ministry; sleep centers do not tend to offer less expensive level III studies as an alternative. This creates a situation whereby treatment outcomes are simply not assessed, or the dentist conducts the study independently, without the assistance or oversight of the sleep medicine professional. Left on their own, many dentists rely upon oximetry and other level IV devices to monitor treatment outcomes, in part because of their limited experience in interpreting the more sophisticated signals obtained by level III devices. Although several level III devices have automated scoring algorithms, the physiological data should still be reviewed by a trained professional. In two patients, the review of the full disclosure recording allowed recognition of complex sleep apnea (i.e., central sleep apnea was revealed posttreatment after the obstructive breathing was resolved) suggesting the importance of having an experienced professional review the data. This study suggests an alternative approach for assessing MAD treatment outcomes that is based on a collaborative relationship between dentists and sleep medicine physician using a limited channel recording system.