A Protocolized Approach to Awake Endoscopy With Advanced Programming to Optimize Hypoglossal Nerve Stimulation.

Hypoglossal nerve stimulation is a treatment option for patients with obstructive sleep apnea who are intolerant to positive airway pressure therapy. In the post-implant period, awake endoscopy with advanced programming (AEAP) can be employed to optimize apnea-hypopnea index reduction and/or patient comfort and usage. The report herein describes awake endoscopy with AEAP as a guide to providers involved in post-implant care. The first 5 consecutive patients were reviewed to provide general understanding of outcomes and safety when implementing such a protocolized approach.

Media Review: Empowered Sleep Apnea: A Handbook for Patients and the People Who Care About Them.

Empowered Sleep Apnea: A Handbook For Patients and the People Who Care About Them by Dr. David E. McCarty, MD, FAASM, and Dr. Ellen Stothard, PhD, published in 2022, is a book that focuses on empowering providers with the knowledge and resources to help patients take charge of their own health. The authors provide practical strategies for managing sleep apnea, including lifestyle modification, CPAP therapy, impact of other disorders, and troubleshooting common issues that arise. This book will be an invaluable resource for health care professionals starting their journey in sleep medicine. CITATION: Shah SB, Stahl S. Media review: Empowered Sleep Apnea: A Handbook for Patients and the People Who Care About Them. J Clin Sleep Med. 2024;20(4):669-670.

Comparison of clinical pathways for hypoglossal nerve stimulation management: in-laboratory titration polysomnography vs home-based efficacy sleep testing.

STUDY OBJECTIVES: We conducted this study to evaluate whether laboratory or home-based hypoglossal nerve stimulation (HNS) management would have equivalent objective and subjective obstructive sleep apnea outcomes 6 months after activation. METHODS: Patients undergoing standard-of-care HNS implantation were randomly assigned in a prospective, multicenter clinical trial to either a 3-month postactivation in-laboratory titration polysomnography (tPSG) or an efficacy home sleep study (eHST) with tPSG by exception for eHST nonresponders at 5 months. Both groups underwent an eHST 6 months postactivation. RESULTS: Sixty patients were randomly assigned. Patients experienced equivalent decreases in the apnea-hypopnea index (mean difference: -0.01 events/h [-8.75, 8.74]) across both groups with HNS; the selection of tPSG or eHST did not associate with therapy response rates (tPSG vs eHST: 63.2% vs 59.1%). The Epworth Sleepiness Scale (median of differences: 1 [-1, 3]) and device usage (median of differences: 0.0 hours [-1.3, 1.3]) outcomes were similar but did not meet a priori statistical equivalence criteria. CONCLUSIONS: This prospective, multicenter, randomized clinical trial demonstrated that patients undergoing HNS implantation experienced statistically equivalent improvements in objective obstructive sleep apnea outcomes and similar improvements in daytime sleepiness regardless of whether they underwent tPSG. HNS titration with tPSG may not be required for all postoperative patients. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Inspire Home Study: Utilization of Home Monitoring During Therapy Optimization in Patients With an Inspire Upper Airway Stimulation System (Comparison of Home Sleep Testing vs. In-lab Polysomnography Testing) (HOME); URL: https://clinicaltrials.gov/ct2/show/NCT04416542; Identifier: NCT04416542. CITATION: Kent D, Huyett P, Yu P, et al. Comparison of clinical pathways for hypoglossal nerve stimulation management: in-laboratory titration polysomnography vs home-based efficacy sleep testing. J Clin Sleep Med. 2023;19(11):1905-1912.

Benefit of adjunctive transoral neuromuscular electrical stimulation with positive airway pressure therapy: a case report.

Combination positive airway pressure therapy and daytime transoral neuromuscular electrical stimulation in the treatment of sleep apnea has not been reported in the literature. We present a case of a patient with poorly controlled sleep apnea despite bilevel positive airway pressure. Adjunctive therapy with daytime neuromuscular electrical stimulation resulted in dramatic reduction of the apnea-hypopnea index with significant improvement in patient's symptoms. CITATION: Stahl SM, Lenet A, Sigua NL. Benefit of adjunctive transoral neuromuscular electrical stimulation with positive airway pressure therapy: a case report. J Clin Sleep Med. 2023;19(11):1971-1974.

Insomnia and Upper Airway Stimulation Therapy Benefit and Adherence: A Case Series.

Obstructive sleep apnea (OSA) and insomnia are common sleep disorders that often occur concurrently. The presence of one of these disorders often negatively impacts the other, including affecting treatment benefit and adherence. While insomnia has been shown to adversely affect positive airway pressure therapy adherence, minimal data are currently available on the effects of insomnia on upper airway stimulation (UAS) therapy for the treatment of OSA. We present two cases that highlight the negative impact of insomnia on UAS therapy usage and OSA management as well as the benefits of insomnia treatment on overall outcomes. Screening for and treatment of insomnia prior to UAS implantation are recommended.

Moving toward standardization: physician reporting of sleep studies.

Detailed primary data collected from sleep studies should lead to specific and clear reports with evidence-based clinical recommendations that, when introduced by sleep medicine specialists, create a window of opportunity to support our non-sleep medicine referring teams and to engage patients and caregivers in their care as recipients of the reports. This is how sleep study reporting differs from other test reports; currently, there is wide variation in how the data collected are presented and summarized. The goal of this document is to offer recommendations for structured reporting of sleep studies. We offer a practical, complete, and relevant document and a structure that can be implemented across sleep centers nationwide and does not burden the interpreter. We anticipate some readers will opine that some of the content is beyond the scope of what the interpreter physician needs to include, while others will propose missing data that they feel should have been included. We feel that the flexibility of the proposal accommodates for this and allows for a "first step" toward standardization of physician reporting of sleep studies. High-quality structured reporting of sleep studies is becoming ever more important for patient care, benefiting patients, caregivers, clinicians, durable medical equipment companies, and payers. CITATION: Lastra AC, Ingram D, Park J, et al. Moving toward standardization: physician reporting of sleep studies. J Clin Sleep Med. 2023;19(3):595-603.

Novel Outcome Analysis Tool for Hypoglossal Nerve Stimulator Sensor Lead Function and Comparison by Incision Type (2 Versus 3).

OBJECTIVE: No reported outcome measures have been established to evaluate sensor lead function in the hypoglossal nerve stimulator (HNS). This study describes the development of novel functional outcome measures for intraoperative sensor electrode function and compares 2-incision and 3-incision outcomes for HNS. METHODS: A retrospective cohort study of 100 consecutive patients who underwent HNS between June 2019 and September 2021. Demographic information, intraoperative findings, and immediate postoperative outcomes were recorded. Structured parameters were developed to compare intraoperative waveforms with six outcome measures utilized: waveform syncing, waveform amplitude, sensory current leakage, shark-fin morphology, cardiac artifact, and overall impression. Two sleep surgeons and two sleep medicine specialists compared all waveforms in a blinded fashion and assigned scores on the Likert Scale. RESULTS: The cohort included 50 three-incision and 50 two-incision patients. Age, gender, average body mass index, comorbidity profiles, and sleep endoscopy findings did not significantly differ between the two groups. No major complications occurred. The interclass-correlation-coefficient was greater than 0.7 for all comparisons (good to very good interrater reliability). There was no difference in waveform amplitude, cardiac artifact, sensory current leakage, or shark-fin morphology between the two groups. Waveform syncing and overall impression were statistically better in the 2-incision cohort. CONCLUSIONS: This study is the first to define a structured method of HNS sensor electrode outcome measurement and showed consistent measures by surgeons and sleep medicine specialists. This article supports the transition to the 2-incision technique among surgeons for placement of the sensor lead. Consideration should be given to utilizing this novel tool in the clinical/research setting and validating these measures moving forward. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:423-430, 2023.

Prevalence of insomnia and restless legs syndrome in patients with upper airway stimulation therapy and effects on treatment outcomes.

OBJECTIVE: This study aims to explore the prevalence of insomnia and restless legs syndrome (RLS) and the possible effects of these conditions on treatment adherence and outcomes in patients with upper airway stimulation (UAS) therapy for the treatment of obstructive sleep apnea. METHODS: Consecutive patients who underwent UAS system implantation were retrospectively studied. Patients without insomnia or RLS, insomnia, RLS, and both insomnia and RLS were compared. The apnea-hypopnea index (AHI), in-lab UAS titration data, Epworth Sleepiness Scale (ESS), and adherence to UAS therapy were compared. RESULTS: Sixty-four patients who had UAS implantation and completed post-implant in-lab UAS titration were identified. Insomnia was present in 47%, RLS in 28%, and both insomnia and RLS in 14%. During in-lab titration, the AHI improved for all groups and did not differ across groups. The arousal index on in-lab titration was higher in patients with both RLS and insomnia compared to those without these conditions. At the time of the in-lab titration, the hours of UAS therapy usage were reduced for patients with RLS (4.7 ± 1.9 h/night, p = 0.027) compared to those without RLS (6.0 ± 2.0 h/night). The ESS was higher in patients with RLS compared to those without RLS at in-lab titration. CONCLUSION: Insomnia and RLS are common in patients using UAS therapy. A decrease in UAS usage and higher ESS were present in patients with RLS. Further research evaluating the long-term effects of insomnia and RLS in UAS therapy usage and benefit is needed.

A Repeat-Associated Small RNA Controls the Major Virulence Factors of Helicobacter pylori.

Many bacterial pathogens regulate their virulence genes via phase variation, whereby length-variable simple sequence repeats control the transcription or coding potential of those genes. Here, we have exploited this relationship between DNA structure and physiological function to discover a globally acting small RNA (sRNA) regulator of virulence in the gastric pathogen Helicobacter pylori. Our study reports the first sRNA whose expression is affected by a variable thymine (T) stretch in its promoter. We show the sRNA post-transcriptionally represses multiple major pathogenicity factors of H. pylori, including CagA and VacA, by base pairing to their mRNAs. We further demonstrate transcription of the sRNA is regulated by the nickel-responsive transcriptional regulator NikR (thus named NikS for nickel-regulated sRNA), thereby linking virulence factor regulation to nickel concentrations. Using in-vitro infection experiments, we demonstrate NikS affects host cell internalization and epithelial barrier disruption. Together, our results show NikS is a phase-variable, post-transcriptional global regulator of virulence properties in H. pylori.

Evaluating the feasibility of implementing a Telesleep pilot program using two-tiered external facilitation.

BACKGROUND: Obstructive sleep apnea (OSA) can negatively impact patients' health status and outcomes. Positive airway pressure (PAP) reverses airway obstruction and may reduce the risk of adverse outcomes. Remote monitoring of PAP (as opposed to in-person visits) may improve access to sleep medicine services. This study aimed to evaluate the feasibility of implementing a clinical program that delivers treatment for OSA through PAP remote monitoring using external facilitation as an implementation strategy. METHODS: Participants included patients with OSA at a Veteran Affairs Medical Center (VAMC). PAP adherence and clinical disease severity on treatment (measured by the apnea hypopnea index [AHI]) were the preliminary effectiveness outcomes across two delivery models: usual care (in-person) and Telehealth nurse-delivered remote monitoring. We also assessed visit duration and travel distance. A prospective, mixed-methods evaluation examined the two-tiered external facilitation implementation strategy. RESULTS: The pilot project included N = 52 usual care patients and N = 38 Telehealth nurse-delivered remote monitoring patients. PAP adherence and disease severity were similar across the delivery modalities. However, remote monitoring visits were 50% shorter than in-person visits and saved a mean of 72 miles of travel (median = 45.6, SD = 59.0, mode = 17.8, range 5.4-220). A total of 62 interviews were conducted during implementation with a purposive sample of 12 clinical staff involved in program implementation. Weekly external facilitation delivered to both front-line staff and supervisory physicians was necessary to ensure patient enrollment and treatment. Synchronized, "two-tiered" facilitation at the executive and coordinator levels proved crucial to developing the clinical and administrative infrastructure to support a PAP remote monitoring program and to overcome implementation barriers. CONCLUSIONS: Remote PAP monitoring had similar efficacy to in-person PAP services in this Veteran population. Although external facilitation is a widely-recognized implementation strategy in quality improvement projects, less is known about how multiple facilitators work together to help implement complex programs. Two-tiered facilitation offers a model well-suited to programs where innovations span disciplines, disrupt professional hierarchies (such as those between service chiefs, clinicians, and technicians) and bring together providers who do not know each other, yet must collaborate to improve access to care.

Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study.

BACKGROUND: Wake-up stroke (WUS) accounts for a quarter of all ischemic strokes. Its conspicuous occurrence during sleep suggests that WUS may be associated with obstructive sleep apnea (OSA). We investigated the potential association among WUS, OSA, and measures of sympathetic hyperactivity. METHODS: This is a cross-sectional analysis of data from the Sleep Apnea in Transient Ischemic Attack and Stroke (SLEEP TIGHT) study. Ischemic stroke patients were divided into WUS and non-WUS groups. Participants underwent polysomnography and ambulatory blood pressure monitoring. Collected data included demographic, medical, stroke characteristics (including severity by National Institutes of Health Stroke Scale), cholesterol, serum catecholamines, C-reactive protein, interleukin-6, B-type natriuretic peptide, blood pressure, and polysomnographic (apnea-hypopnea index (AHI); measures of hypoxia). Because both stroke and OSA affect men and women to varying degrees, the cohort was considered as a whole and by gender stratification. RESULTS: Among 164 participants, 30.3% had WUS. The mean age was 62.0 ± 11.3 and the mean body mass index was 30.2 ± 7.9 kg/m2. One-hundred-and-five participants (63.6%) were males and 92 participants (56.8%) were Caucasian. Neither AHI nor OSA (AHI ≥5) frequency differed between WUS and non-WUS groups. Men tended to be more likely than women to have WUS (74.0 vs. 59.6%; p = 0.08), but this was not statistically significant. In gender-stratified analyses, men with WUS compared to men with non-WUS had significantly higher rates of severe OSA (AHI >30: 45.0 vs. 17.6%; p = 0.03) and tended toward more 3% oxygen desaturation events (57.0 ± 63.9 vs. 31.8 ± 22.9; p = 0.06). These differences were not seen in women. WUS patients tended to be of the male gender (74.0 vs. 59.6%; p = 0.08). History of stroke, hypertension, diabetes, dyslipidemia, or atrial fibrillation, serum catecholamines, and inflammatory biomarkers was no different between the groups. Low-density lipoprotein (LDL) was significantly higher in WUS (114.5 ± 36.3 vs. 101.4 ± 37.6; p = 0.04). Baseline diastolic blood pressure (DBP) was significantly greater in the WUS group. There was no difference in systolic or ambulatory blood pressure (including nighttime blood pressure) between WUS and non-WUS groups. CONCLUSIONS: WUS may be associated with severe OSA with more oxygen desaturation in men but not in women. WUS may be associated with high DBP and increased LDL cholesterol.

Infarct location and sleep apnea: evaluating the potential association in acute ischemic stroke.

BACKGROUND: The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. METHODS: Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. RESULTS: Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. CONCLUSIONS: These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients.

Isolated ocular disease is associated with decreased mucolipin-1 channel conductance.

PURPOSE: To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and clinical abnormalities restricted to the eye who also had achlorhydria with elevated blood gastrin levels. METHODS: In addition to a detailed neuro-ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was experimentally expressed in liposomes and its channel properties studied in vitro. RESULTS: The patient was a compound heterzygote for c.920delT and c.1615delG. Detailed neuro-ophthalmic examination including electroretinography showed him to have a typical retinal dystrophy predominantly affecting rod and bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the c.1615delG mutated channel had significantly reduced conductance compared with wild-type mucolipin-1, whereas the inhibitory effect of low pH and amiloride remained intact. CONCLUSIONS: These findings suggest that reduced channel conductance is relatively well tolerated by the brain during development, whereas retinal cells and stomach parietal cells require normal protein function. MLIV should be considered in patients with retinal dystrophy of unknown cause and screened for using blood gastrin levels.

An implicit enumeration method for an exact test of weighted kappa.

The kappa coefficient is one of the most widely used measures for evaluating the agreement between two raters asked to assign N objects to one of K nominal categories. Weighted versions of kappa enable partial credit to be awarded for near agreement, most notably in the case of ordinal categories. An exact significance test for weighted kappa can be conducted by enumerating all rater agreement tables with the same fixed marginal frequencies as the observed table, and accumulating the probabilities for all tables that produce a weighted kappa index that is greater than or equal to the observed measure. Unfortunately, complete enumeration of all tables is computationally unwieldy for modest values of N and K. We present an implicit enumeration algorithm for conducting an exact test of weighted kappa, which can be applied to tables of non-trivial size. The algorithm is particularly efficient for 'good' to 'excellent' values of weighted kappa that typically have very small p-values. Therefore, our method is beneficial for situations where resampling tests are of limited value because the number of trials needed to estimate the p-value tends to be large.