Long-Term Generator Replacement Experience in Hypoglossal Nerve Stimulator Therapy Recipients With CPAP-Intolerant Obstructive Sleep Apnea.

OBJECTIVE: In the last decade, hypoglossal nerve stimulation (HNS) has emerged as a therapeutic alternative for patients with obstructive sleep apnea. The original clinical trial cohorts are entering the phase of expected battery depletion (8-12 years). This study aimed to examine the surgical experience with implantable pulse generator (IPG) replacements and the associated long-term therapy outcomes. STUDY DESIGN: Retrospective analysis of patients from the original clinical trial databases (STAR, German post-market) who were followed in the ongoing ADHERE registry. SETTING: International multicenter HNS registry. METHODS: The ADHERE registry and clinical trial databases were cross-referenced to identify the serial numbers of IPGs that were replaced. Data collection included demographics, apnea-hypopnea index (AHI), therapy use, operative times, and adverse events. RESULTS: Fourteen patients underwent IPG replacement 8.3 ± 1.1 years after their initial implantation. Body mass index was unchanged between the original implant and IPG replacement (29 ± 4 vs 28 ± 2 kg/m2 , p = .50). The mean IPG replacement operative time was shorter than the original implant (63 ± 50 vs 154 ± 58 minutes, p < .002); however, 2 patients required stimulation lead replacement which significantly increased operative time. For patients with available AHI and adherence data, the mean change in AHI from baseline to latest follow-up (8.7 ± 1.1 years after de novo implant) was -50.06%, and the mean therapy use was 7.2 hours/night. CONCLUSION: IPG replacement surgery was associated with low complications and shorter operative time. For patients with available outcomes data, adherence and efficacy remained stable after 9 years of follow-up.

Electric field aspects in hypoglossal nerve stimulation for obstructive sleep apnea: A bilateral electrophysiological evaluation of unilateral electrode configuration changes.

Hypoglossal nerve stimulation is an established treatment option for obstructive sleep apnea in selected patients. A unilateral hypoglossal nerve stimulation system was approved a decade ago, yet the physiological effect of unilateral hypoglossal stimulation on bilateral tongue motion remains unclear. This study examined how electrode configuration, stimulation cuff position, or body mass index influenced the contralateral genioglossus electromyography (EMG) signal. Twenty-nine patients underwent three EMG recordings in a polysomnographic setting after being implanted with a unilateral hypoglossal nerve stimulator for at least 6 months. The ratio of EMG signals between the ipsi- and contralateral sides was evaluated. No difference in EMG signals was demonstrated based on electrode configurations, stimulation-cuff position, body-mass-index, or sleep apnea severity, even in patients with right tongue protrusion only. Our findings may be explained by a significant level of cross-innervation and by a smaller and less variable circumferential electric field than expected based on prior biophysical models. A patient's individual anatomy needs to be considered during therapy titration in order to achieve an optimal response.

Hypoglossal nerve stimulation versus positive airway pressure therapy for obstructive sleep apnea.

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness. METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated. RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP. CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

Patient Related Outcome and Therapy Effects in Stimulation Treatment of Sleep-Related Breathing Disorders. / Patienten relevanter Nutzen und Therapieeffekte in der Stimulationstherapie bei schlafbezogenen Atmungsstörungen.

Several neurostimulation devices exist for the treatment of various sleep-related breathing diseases. The most data for hypoglossal nerve stimulation (HNS) in the therapy of obstructive sleep apnea (OSA) derive the HNS with respiratory sensing. Herewith, daytime sleepiness measured with the Epworth Sleepiness Scale (ESS) was improved in several publications by 5 points with a stability shown for up to several years. Sleep related quality of life, documented with the Functional Outcomes of Sleep Questionnaire, increased by 2 points. In many cohorts showed a mean usage of 5 to 6 hours per night. Under the consideration of shorter follow-ups and smaller group sizes, the ESS improved by 4 under unilateral continuous HNS and by 3 under bilateral HNS. Transvenous stimulation of the phrenic nerve is approved for the treatment in central sleep apnea. In a pivotal trial with 5 year follow-up data, an ESS reduction is documented by 3 points. There is one publication describing a usage of more than 5 hours. The daytime enoral neuromuscular electrical therapy improved ESS (2 points) and sleep-related quality of life of the snoring patients and the bed partner. The daytime training for the effects during the night adherence is given with 83%. For all described devices, there are running or announced studies and/or registry trials that consider patient related outcome.

Hypoglossal nerve stimulation for obstructive sleep apnea: updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery.

Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize the complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions, whereat, minimal reporting standards to document outcome and usage are recommended.

Impulse Configuration in Hypoglossal Nerve Stimulation in Obstructive Sleep Apnea: The Effect of Modifying Pulse Width and Frequency.

OBJECTIVES: Hypoglossal nerve stimulation is an effective treatment option for obstructive sleep apnea (OSA) in positive airway pressure therapy failure. Nonetheless, data regarding the functional effect of modifying stimulation parameters within each electrode configuration are limited. MATERIALS AND METHODS: In a retrospective study of 76 patients with 12 months or more follow-up, functional tongue protrusion thresholds were compared for pulse width and frequency configurations of 90 µsec 33 Hz vs 120 µsec 40 Hz. The number of tolerated voltage amplitude steps between sensation, functional, and subdiscomfort thresholds were assessed for both settings as well as impedances. RESULTS: The overall cohort showed improvement in OSA metrics: median apnea-hypopnea index from 30.0/hour to 18.6/hour and Epworth Sleepiness Scale from 13.5 to 7.6. For both bipolar and unipolar electrode configurations, the stimulation amplitude required for functional tongue protrusion was significantly reduced when the pulse width and frequency were converted from 90 µsec 33 Hz to 120 µsec 40 Hz (p < 0.001). Nevertheless, the number of voltage amplitude steps from sensation, functional, to subdiscomfort thresholds did not differ between the two settings. The ratio of automatically derived impedances between bipolar and unipolar electrode configurations was relevantly correlated with the ratio of functional thresholds at these parameters. CONCLUSION: Changing the stimulation parameters may lower the voltage requirements while maintaining the same effect on tongue protrusion. Changing these stimulation parameters does not affect the range of tolerated impulse steps between functional and subdiscomfort thresholds. Future technical appliances could help estimate functional thresholds at different electrode configurations for each patient by automatically measuring impedances.

Impact of Body Mass Index and Discomfort on Upper Airway Stimulation: ADHERE Registry 2020 Update.

OBJECTIVES/HYPOTHESIS: To provide the ADHERE registry Upper Airway Stimulation (UAS) outcomes update, including analyses grouped by body mass index (BMI) and therapy discomfort. STUDY DESIGN: Prospective observational study. METHODS: ADHERE captures UAS outcomes including apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), therapy usage, patient satisfaction, clinician assessment, and safety over a 1-year period. BMI ≤32 kg/m2 (BMI32 ) and 32 < BMI ≤35 kg/m2 (BMI35 ) group outcomes were examined. RESULTS: One thousand eight hundred forty-nine patients enrolled in ADHERE, 1,019 reached final visit, 843 completed the visit. Significant changes in AHI (-20.9, P < .0001) and ESS (- 4.4, P < .0001) were demonstrated. Mean therapy usage was 5.6 ± 2.2 hr/day. Significant therapy use difference was present in patients with reported discomfort versus no discomfort (4.9 ± 2.5 vs. 5.7 ± 2.1 hr/day, P = .01). Patients with discomfort had higher final visit mean AHI versus without discomfort (18.9 ± 18.5 vs. 13.5 ± 13.7 events/hr, P = .01). Changes in AHI and ESS were not significantly different. Serious adverse events reported in 2.3% of patients. Device revision rate was 1.9%. Surgical success was less likely in BMI35 versus BMI32 patients (59.8% vs. 72.2%, P = .02). There was a significant therapy use difference: 5.8 ± 2.0 hr/day in BMI32 versus 5.2 ± 2.2 hr/day in BMI35 (P = .028). CONCLUSIONS: Data from ADHERE demonstrate high efficacy rates for UAS. Although surgical response rate differs between BMI32 and BMI35 patient groups, the AHI and ESS reduction is similar. Discomfort affects therapy adherence and efficacy. Thus, proper therapy settings adjustment to ensure comfort is imperative to improve outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2616-2624, 2021.

A critical review of incobotulinumtoxinA in the treatment of chronic sialorrhea in pediatric patients.

INTRODUCTION: Sialorrhea, also known as hypersalivation, ptyalis, or drooling, results in physical and psychosocial complications that may have a significant negative impact on quality of life for both the patient and their caregiver. The goal of pharmacological treatment is to reduce excessive salivary flow, while maintaining a moist and healthy oral cavity; until recently, however, few of the agents used to treat chronic sialorrhea have been approved in pediatric patients. AREAS COVERED: This article summarizes early evidence for the use of botulinum neurotoxin A formulations in the treatment of children/adolescents with chronic sialorrhea, and findings of the recently completed phase III trial of incobotulinumtoxinA in this indication. Alternative therapies are also briefly discussed. EXPERT OPINION: IncobotulinumtoxinA is the first botulinum neurotoxin A to be approved for the treatment of chronic sialorrhea in children and adults, following the results of phase III trials that demonstrate the efficacy and safety of the drug in these patients. The authors expect that the positive findings will result in updates to clinical guidelines for the treatment of children with chronic sialorrhea. ABBREVIATIONS: AE, adverse event; AESI, adverse event of special interest; BoNT/A, botulinum neurotoxin A; CI, confidence interval; CP, cerebral palsy; DIS, drooling impact scale; DQ, drooling quotient; DSFS, Drooling Severity and Frequency Scale; GICS, Global Impression of Change Scale; LS, least squares; mTDS, modified Teacher's drooling scale; NR, not reported; PD, Parkinson's disease; SAE, serious adverse event; SE, standard error; SIAXI, Sialorrhea in Adults Xeomin Investigation; SIPEXI, Sialorrhea Pediatric Xeomin Investigation; SNAP-25, synaptosomal associated protein-25; TBI, traumatic brain injury; TDS, Teacher Drooling Scale; USA, United States of America; uSFR, unstimulated Salivary Flow Rate; VAS, visual analog scale.

Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions, and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel. CITATION: Suurna MV, Jacobowitz O, Chang J, et al. Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum. J Clin Sleep Med. 2021;17(12):2477-2487.

Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Individuals with obstructive sleep apnea (OSA), characterized by frequent sleep disruptions from tongue muscle relaxation and airway blockage, are known to benefit from on-demand electrical stimulation of the hypoglossal nerve. Hypoglossal nerve stimulation (HNS) therapy, which activates the protrusor muscles of the tongue during inspiration, has been established in multiple clinical studies as safe and effective, but the mechanistic understanding for why some stimulation parameters work better than others has not been thoroughly investigated. METHODS: In this study, we developed a detailed biophysical model that can predict the spatial recruitment of hypoglossal nerve fascicles and axons within these fascicles during stimulation through nerve cuff electrodes. Using this model, three HNS programming scenarios were investigated including grouped cathode (---), single cathode (o-o), and guarded cathode bipolar (+-+) electrode configurations. RESULTS: Regardless of electrode configuration, nearly all hypoglossal nerve axons circumscribed by the nerve cuff were recruited for stimulation amplitudes <3 V. Within this range, monopolar configurations required lower stimulation amplitudes than the guarded bipolar configuration to elicit action potentials within hypoglossal nerve axons. Further, the spatial distribution of the activated axons was more uniform for monopolar versus guarded bipolar configurations. CONCLUSIONS: The computational models predicted that monopolar HNS provided the lowest threshold and the least sensitivity to rotational angle of the nerve cuff around the hypoglossal nerve; however, this setting also increased the likelihood for current leakage outside the nerve cuff, which could potentially activate axons in unintended branches of the hypoglossal nerve. CLINICAL TRIAL REGISTRATION: NCT01161420.

Home Sleep Testing to Direct Upper Airway Stimulation Therapy Optimization for Sleep Apnea.

OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) is a well-established treatment option for obstructive sleep apnea (OSA). This study aimed to determine if there are benefits in performing a home sleep test (HST) to evaluate postoperative sUAS effectiveness after patient acclimatization compared to the generally used polysomnography (PSG) titration, as measured by long-term follow-up outcomes. STUDY DESIGN: Retrospective comparative cohort analysis. METHODS: We conducted an analysis of consecutive patients at our center who had completed a 6-month follow-up (month 6 [M6]) and recorded data from M6, month 12 (M12), and month 24 (M24). After device activation, we performed an HST with the patient's stimulation settings, and measured the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and device usage. These values were compared to patients who had undergone PSG-based device titration. RESULTS: Baseline values of the initial 131 patients show high ESS and moderate OSA. At the 2-month time point of the HST, nearly half of the patients (46.2%) reached an AHI ≤15/hr, and approximately a fifth (19.2%) reached <5/hr. The PSG and HST groups differed in median ESS at M24, but no other differences were observed for ESS at M6 and M12. Both groups showed similar AHI, oxygen desaturation, and usage hours per week. CONCLUSIONS: Adjusting therapy by using the HST technique after device activation and acclimatization has clinical and economic advantages. These advantages are contingent on several conditions being met when deviating from the standard device protocol, including precise communication with the referring sleep medicine physicians, especially their role in helping with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1375-E1379, 2021.

Evaluation of Surgical Learning Curve Effect on Obstructive Sleep Apnea Outcomes in Upper Airway Stimulation.

OBJECTIVE: An increasing number of facilities offer Upper Airway Stimulation (UAS) with varying levels of experience. The goal was to quantify whether a surgical learning curve exists in operative or sleep outcomes in UAS. METHODS: International multi-center retrospective review of the ADHERE registry, a prospective international multi-center study collecting UAS outcomes. ADHERE registry centers with at least 20 implants and outcomes data through at least 6-month follow-up were reviewed. Cases were divided into two groups based on implant order (the first 10 or second 10 consecutive implants at a given site). Group differences were assessed using Mann-Whitney U-tests, Chi-squared tests, or Fisher's Exact tests, as appropriate. A Mann-Kendall trend test was used to detect if there was a monotonic trend in operative time. Sleep outcome equivalence between experience groups was assessed using the two one-sided tests approach. RESULTS: Thirteen facilities met inclusion criteria, contributing 260 patients. Complication rates did not significantly differ between groups (P = .808). Operative time exhibited a significant downward trend (P < .001), with the median operative time dropping from 150 minutes for the first 10 implants to 134 minutes for the subsequent 10 implants. The decrease in AHI from baseline to 12-month follow-up was equivalent between the first and second ten (22.8 vs 21.2 events/hour, respectively, P < .001). Similarly, the first and second ten groups had equivalent ESS decreases at 6 months (2.0 vs 2.0, respectively, P < .001). ESS outcomes remained equivalent for those with data through 12-months. CONCLUSIONS: Across the centers' first 20 implants, an approximately 11% reduction operative time was identified, however, no learning curve effect was seen for 6-month or 12-month AHI or ESS over the first twenty implants. Ongoing monitoring through the ADHERE registry will help measure the impact of evolving provider and patient specific characteristics as the number of implant centers increases.

Die Stimulation des Nervus hypoglossus in der Behandlung der obstruktiven Schlafapnoe ­ Aktualisiertes Positionspapier der Arbeitsgemeinschaft Schlafmedizin der DGHNO-KHC.

Hypoglossal nerve stimulation for obstructive sleep apnea - Updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions whereat minimal reporting standards to document outcome and usage are recommended.

Selective suppression of rapid eye movement sleep increases next-day negative affect and amygdala responses to social exclusion.

Healthy sleep, positive general affect, and the ability to regulate emotional experiences are fundamental for well-being. In contrast, various mental disorders are associated with altered rapid eye movement (REM) sleep, negative affect, and diminished emotion regulation abilities. However, the neural processes mediating the relationship between these different phenomena are still not fully understood. In the present study of 42 healthy volunteers, we investigated the effects of selective REM sleep suppression (REMS) on general affect, as well as on feelings of social exclusion, cognitive reappraisal (CRA) of emotions, and their neural underpinnings. Using functional magnetic resonance imaging we show that, on the morning following sleep suppression, REMS increases general negative affect, enhances amygdala responses and alters its functional connectivity with anterior cingulate cortex during passively experienced experimental social exclusion. However, we did not find effects of REMS on subjective emotional ratings in response to social exclusion, their regulation using CRA, nor on functional amygdala connectivity while participants employed CRA. Our study supports the notion that REM sleep is important for affective processes, but emphasizes the need for future research to systematically investigate how REMS impacts different domains of affective experience and their neural correlates, in both healthy and (sub-)clinical populations.

Results of the ADHERE upper airway stimulation registry and predictors of therapy efficacy.

OBJECTIVE/HYPOTHESIS: The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA. STUDY DESIGN: Cohort Study. METHODS: Demographic and sleep study data collection occurred at baseline, implantation visit, post-titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of therapy response, defined as ≥50% decrease in Apnea-Hypopnea Index (AHI) and AHI ≤20 at the 12-month visit. RESULTS: The registry has enrolled 1,017 patients from October 2016 through February 2019. Thus far, 640 patients have completed their 6-month follow-up and 382 have completed the 12-month follow-up. After 12 months, median AHI was reduced from 32.8 (interquartile range [IQR], 23.6-45.0) to 9.5 (IQR, 4.0-18.5); mean, 35.8 ± 15.4 to 14.2 ± 15.0, P < .0001. Epworth Sleepiness Scale was similarly improved from 11.0 (IQR, 7-16) to 7.0 (IQR, 4-11); mean, 11.4 ± 5.6 to 7.2 ± 4.8, P < .0001. Therapy usage was 5.6 ± 2.1 hours per night after 12 months. In a multivariate model, only female sex and lower baseline body mass index remained as significant predictors of therapy response. CONCLUSIONS: Across a multi-institutional study, UAS therapy continues to show significant improvement in subjective and objective OSA outcomes. This analysis shows that the therapy effect is durable and adherence is high. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1333-1338, 2020.

Long-term follow-up of the German post-market study for upper airway stimulation for obstructive sleep apnea.

PURPOSE: Upper airway stimulation (UAS) is an effective treatment for obstructive sleep apnea (OSA) in positive airway pressure (PAP) failure. Most reports have presented short-term data, so long-term safety and efficacy reports are rare. The German post-market study (G-PMS) has followed approximately 60 patients from three implanting centers for several years. METHODS: Patients with OSA and PAP failure qualified for the G-PMS by the absence of obesity class 2 an AHI between 15 and 65 events/h and absence of complete concentric collapse at the velum during drug-induced sleep endoscopy. Optional 2- and 3-year follow-ups after implantation were collected during routine clinical practice. We measured respiratory parameters such as apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) and daytime sleepiness using the Epworth sleepiness scale (ESS) in a per protocol analysis. Usage was calculated from device-downloaded reports. Device-related complications were documented. RESULTS: Of the 60 original patients, 41 returned for 2-year follow-up, and 38 for 3 years. About 76% at 2 years and 68% at 3 years met the criterion of therapy success defined as an AHI below 15/h. The median AHI was reduced from 28.6/h (baseline) to 9.0/h (2 years) and 10.0/h (3 years); whereas median ODI decreased from 27.0 to 6.3/h (2 years), and 8.3/h (3 years). Median ESS improved from baseline 13 points to 4 (2 years) and 6 (3 years). Usage was stable at approximately 45 h per week at 2 and 3 years. Serious device-related adverse events were rare, with two-device explantation between 12 to 36 months postoperatively. CONCLUSIONS: The German multi-center long-term outcomes compare favorably with previously published studies. Respiratory and sleepiness efficacy outcomes were sustained over 2 and 3 years, with a favorable safety profile, supporting the safety and efficacy of a chronic implantable therapy.

Previous Surgery and Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To examine whether previous palate or hypopharyngeal surgery was associated with efficacy of treatment of obstructive sleep apnea with hypoglossal nerve stimulation. STUDY DESIGN: Cohort (retrospective and prospective). SETTING: Eleven academic medical centers. SUBJECTS AND METHODS: Adults treated with hypoglossal nerve stimulation were enrolled in the ADHERE Registry. Outcomes were defined by the apnea-hypopnea index (AHI), in 3 ways: change in the AHI and 2 definitions of therapy response requiring ≥50% reduction in the AHI to a level <20 events/h (Response20) or 15 events/h (Response15). Previous palate and hypopharyngeal (tongue, epiglottis, or maxillofacial) procedures were documented. Linear and logistic regression examined the association between previous palate or hypopharyngeal surgery and outcomes, with adjustment for age, sex, and body mass index. RESULTS: The majority (73%, 217 of 299) had no previous palate or hypopharyngeal surgery, while 25% and 9% had previous palate or hypopharyngeal surgery, respectively, including 6% with previous palate and hypopharyngeal surgery. Baseline AHI (36.0 ± 15.6 events/h) decreased to 12.0 ± 13.3 at therapy titration (P < .001) and 11.4 ± 12.6 at final follow-up (P < .001). Any previous surgery, previous palate surgery, and previous hypopharyngeal surgery were not clearly associated with treatment response; for example, any previous surgery was associated with a 0.69 (95% CI: 0.37, 1.27) odds of response (Response20 measure) at therapy titration and a 0.55 (95% CI: 0.22, 1.34) odds of response (Response20 measure) at final follow-up. CONCLUSION: Previous upper airway surgery was not clearly associated with efficacy of hypoglossal nerve stimulation.

Hypersalivation: update of the German S2k guideline (AWMF) in short form.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes to activate compensation mechanisms as long compliances are given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the EU. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long-lasting saliva reduction. Here, a phase III trial is completed for incobotulinum toxin A and, in the US, is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3D techniques to minimize tissue damage. Therapy effects and symptom severity have to be followed, especially in cases with underlying neurodegenerative disease.

Clinical and Economic Benefits of Upper Airway Stimulation for Obstructive Sleep Apnea in a European Setting.

BACKGROUND: Upper airway stimulation (UAS) is a treatment approach for patients with moderate-to-severe obstructive sleep apnea who cannot adhere to continuous positive airway pressure therapy. OBJECTIVE: The objective was to evaluate added patient benefit and cost-effectiveness of UAS in the German health care system. METHODS: We used a decision-analytic Markov model to project major adverse cardiovascular or cerebrovascular events (myocardial infarction [MI] or stroke), motor vehicle collision (MVC), mortality, quality-adjusted life years (QALYs), and costs. The assumed reduction in the apnea-hypopnea index with UAS compared to no treatment is based on German real-world data. Other input data were derived from the literature, public statistics, and multivariate regression. Cost-effectiveness was evaluated in Euros per QALY gained, both discounted at 3%. RESULTS: UAS was projected to reduce event risks (10-year relative risk for stroke, MI, cardiovascular death, and MVC: 0.76, 0.64, 0.65, and 0.34, respectively), and to increase survival by 1.27 years. While the UAS strategy incurred an additional 1.02 QALYs within the patient lifetime, there were also additional costs of EUR 45,196, resulting in an incremental cost-effectiveness ratio of EUR 44,446 per QALY gained. -Conclusions: In the present model-based analysis, UAS therapy provides meaningful benefit to patient-relevant endpoints and is a cost-effective therapy in the German setting.

Post-approval upper airway stimulation predictors of treatment effectiveness in the ADHERE registry.

Upper airway stimulation (UAS) has been shown to reduce severity of obstructive sleep apnoea. The aim of this study was to identify predictors of UAS therapy response in an international multicentre registry.Patients who underwent UAS implantation in the United States and Germany were enrolled in an observational registry. Data collected included patient characteristics, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS), objective adherence, adverse events and patient satisfaction measures. Post hoc univariate and multiple logistic regression were performed to evaluate factors associated with treatment success.Between October 2016 and January 2018, 508 participants were enrolled from 14 centres. Median AHI was reduced from 34 to 7 events·h-1, median ESS reduced from 12 to 7 from baseline to final visit at 12-month post-implant. In post hoc analyses, for each 1-year increase in age, there was a 4% increase in odds of treatment success. For each 1-unit increase in body mass index (BMI), there was 9% reduced odds of treatment success. In the multivariable model, age persisted in serving as statistically significant predictor of treatment success.In a large multicentre international registry, UAS is an effective treatment option with high patient satisfaction and low adverse events. Increasing age and reduced BMI are predictors of treatment response.