Publications by authors named "Timothy I Morgenthaler"

124 Publications

Optimal Noninvasive Medicare Access Promotion: Patients With Central Sleep Apnea: A Technical Expert Panel Report From the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

Chest 2021 Jul 30. Epub 2021 Jul 30.

Department of Medicine, Veterans Affairs Medical Center, Martinsburg, WV.

This document summarizes suggestions of the central sleep apnea (CSA) Technical Expert Panel working group. This paper shares our vision for bringing the right device to the right patient at the right time. For patients with CSA, current coverage criteria do not align with guideline treatment recommendations. For example, CPAP and oxygen therapy are recommended but not covered for CSA. On the other hand, bilevel positive airway pressure (BPAP) without a backup rate may be a covered therapy for OSA, but it may worsen CSA. Narrow coverage criteria that require near elimination of obstructive breathing events on CPAP or BPAP in the spontaneous mode, even if at poorly tolerated pressure levels, may preclude therapy with BPAP with backup rate or adaptive servoventilation, even when those devices provide demonstrably better therapy. CSA is a dynamic disorder that may require different treatments over time, sometimes switching from one device to another; an example is switching from BPAP with backup rate to an adaptive servoventilation with automatic end-expiratory pressure adjustments, which may not be covered. To address these challenges, we suggest several changes to the coverage determinations, including: (1) a single simplified initial and continuing coverage definition of CSA that aligns with OSA; (2) removal of hypoventilation terminology from coverage criteria for CSA; (3) all effective therapies for CSA should be covered, including oxygen and all PAP devices with or without backup rates or servo-mechanisms; and (4) patients shown to have a suboptimal response to one PAP device should be allowed to add oxygen or change to another PAP device with different capabilities if shown to be effective with testing.
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http://dx.doi.org/10.1016/j.chest.2021.07.039DOI Listing
July 2021

Does testing for sleep-disordered breathing pre-discharge versus post-discharge result in different treatment outcomes?

J Clin Sleep Med 2021 Jun 21. Epub 2021 Jun 21.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester MN.

Study Objectives: Treatment of sleep-disordered breathing (SDB) may improve health related outcomes post-discharge. However timely definitive sleep testing and provision of ongoing therapy has been a challenge. Little is known about how the time of testing-during hospitalization vs. after discharge-affects important outcomes such as treatment adherence.

Methods: We conducted a 10-year retrospective study of hospitalized adults who received an inpatient sleep medicine consultation for SDB and subsequent sleep testing. We divided them into inpatient and outpatient sleep testing cohorts and studied their clinical characteristics, follow-up and PAP adherence, and hospital readmission.

Results: Of 485 patients, 226 (47%) underwent inpatient sleep testing and 259 (53%) had outpatient sleep testing. The median age was 68 years old (IQR=57-78), and 29.6% were females. The inpatient cohort had a higher Charlson Comorbidity Index (CCI) (4 [3-6] vs 3[2-5], p=<0.0004). A higher CCI (HR=1.14, 95%CI:1.03-1.25, p=0.001), BMI (HR=1.03, 95%CI:1.0-1.05, p=0.008) and stroke (HR=2.22, 95%CI:1.0-4.9, p=0.049) were associated with inpatient sleep testing. The inpatient cohort kept fewer follow-up appointments (39.90% vs 50.62%, p=0.03) however PAP adherence was high among those keeping follow-up appointments (88.9% [inpatient] vs 85.71% [outpatient], p=0.55). The inpatient group had an increased risk for death (HR: 1.82 95%CI 1.28-2.59, p=<0.001) but readmission rates did not differ.

Conclusions: Medically complex patient were more likely to receive inpatient sleep testing but less likely to keep follow-up, which could impact adherence and effectiveness of therapy. Novel therapeutic interventions are needed to increase sleep medicine follow-up post-discharge which may result in improvement in health outcomes in hospitalized patients with SDB.
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http://dx.doi.org/10.5664/jcsm.9450DOI Listing
June 2021

A Practice Redesign Collaborative for Reducing Hospital Readmission for Chronic Obstructive Pulmonary Disease in an Affiliated Network of Health Care Organizations.

Jt Comm J Qual Patient Saf 2021 07 1;47(7):412-421. Epub 2021 Apr 1.

Background: Patients discharged following admissions for acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) frequently require unplanned readmissions, increasing costs and morbidity for thousands of patients suffering from COPD. The Hospital Readmissions Reduction Program provided financial incentives to reduce 30-day readmissions for AE-COPD, but although risk factors for readmission are known, few evidence-based interventions achieve this goal. Members of the Mayo Clinic Care Network (MCCN) formed a collaborative to seek ways to reduce 30-day readmission for patients admitted with AE-COPD.

Methods: Seventeen MCCN organizations participated in an improvement collaborative in 2016 and 2017. Mayo Clinic subject matter experts shared improvement webinars, protocols, and educational materials related to AE-COPD and delivered individualized coaching to facilitate improvement at each site over a six-month engagement. Among other recommended interventions, organizations worked to increase the proportion of COPD patients who had a standardized disease severity staging during admission, inhaler appropriateness evaluations, a COPD treatment action plan, and clinical contact at < 48 hours and 10 ± 4 days postdischarge.

Results: Same-hospital readmission rates improved from 17.7% ± 3.6 to 14.5% ± 4.0 (weighted difference -4.38, p = 0.008, paired t-test). In addition, participating teams stated that the collaborative framework helped them develop strategies that improved patient care and organizational capacity for improvement in other domains.

Conclusion: The collaborative framework, beginning with education delivered in person and via webinars, combined with telephonically delivered coaching and knowledge sharing, assisted most members to improve care. Fourteen of 17 participating sites experienced a reduced AE-COPD readmission rate.
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http://dx.doi.org/10.1016/j.jcjq.2021.03.007DOI Listing
July 2021

Transvenous phrenic nerve stimulation improves central sleep apnea, sleep quality, and quality of life regardless of prior positive airway pressure treatment.

Sleep Breath 2021 Mar 20. Epub 2021 Mar 20.

Mayo Clinic, Rochester, MN, USA.

Study Objective: Positive airway pressure (PAP) therapy for central sleep apnea (CSA) is often poorly tolerated, ineffective, or contraindicated. Transvenous phrenic nerve stimulation (TPNS) offers an alternative, although its impact on previously PAP-treated patients with CSA has not been examined.

Methods: TPNS responses among PAP-naïve and prior PAP-treated patients from the remedē System Pivotal Trial were assessed. Of 151, 56 (37%) used PAP therapy before enrolling in the trial. Patients were implanted with a TPNS device and randomized to either active or deferred (control) therapy for 6 months before therapy activation. Apnea-hypopnea index (AHI) and patient-reported outcomes (PRO) were assessed at baseline, and 6 and 12 months following active therapy.

Results: Patients had moderate-severe CSA at baseline, which was of greater severity and more symptomatic in the PAP-treated vs. PAP-naïve group (median AHI 52/h vs. 38, central apnea index (CAI) 32/h vs. 18, Epworth Sleepiness Scale 13 vs. 10, fatigue severity scale 5.2 vs. 4.5). Twelve months of TPNS decreased AHI to <20/h and CAI to ≤2/h. Both groups showed reductions in daytime sleepiness and fatigue, improved well-being by patient global assessment, and high therapeutic acceptance with 98% and 94% of PAP-treated and PAP-naïve patients indicating they would undergo the implant again. Stimulation produced discomfort in approximately one-third of patients, yet <5% of prior PAP-treated participants discontinued therapy.

Conclusion: Polysomnographic and clinical responses to TPNS were comparable in PAP-naïve and prior PAP-treated CSA patients. TPNS is a viable therapy across a broad spectrum of CSA patients.

Trial Registration: ClinicalTrials.gov Identifier NCT01816776; March 22, 2013.
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http://dx.doi.org/10.1007/s11325-021-02335-xDOI Listing
March 2021

A comparison of 2 visual methods for classifying obstructive vs central hypopneas.

J Clin Sleep Med 2021 06;17(6):1157-1165

Mayo Clinic, Rochester, Minnesota.

Study Objectives: Rules for classifying apneas as obstructive, central, or mixed are well established. Although hypopneas are given equal weight when calculating the apnea-hypopnea index, classification is not standardized. Visual methods for classifying hypopneas have been proposed by the American Academy of Sleep Medicine and by Randerath et al (Sleep. 2013;36[3]:363-368) but never compared. We evaluated the clinical suitability of the 2 visual methods for classifying hypopneas as central or obstructive.

Methods: Fifty hypopnea-containing polysomnographic segments were selected from patients with clear obstructive or clear central physiology to serve as standard obstructive or central hypopneas. These 100 hypopnea-containing polysomnographic segments were deidentified, randomized, and scored by 2 groups. We assigned 1 group to use the American Academy of Sleep Medicine criteria and the other the Randerath algorithm. After a washout period, re-randomized hypopnea-containing polysomnographic segments were scored using the alternative method. We determined the accuracy (agreement with standard), interrater (Fleiss's κ), and intrarater agreement (Cohen's κ) for obtained scores.

Results: Accuracy of the 2 methods was similar: 67% vs 69.3% for Randerath et al and the American Academy of Sleep Medicine, respectively. Cohen's κ was 0.01-0.75, showing that some raters scored similarly using the 2 methods, while others scored them markedly differently. Fleiss's κ for the American Academy of Sleep Medicine algorithm was 0.32 (95% confidence interval, 0.29-0.36) and for the Randerath algorithm was 0.27 (95% confidence interval, 0.23-0.30).

Conclusions: More work is needed to discover a noninvasive way to accurately characterize hypopneas. Studies like ours may lay the foundation for discovering the full spectrum of physiologic consequences of obstructive sleep apnea and central sleep apnea.
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http://dx.doi.org/10.5664/jcsm.9140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314662PMC
June 2021

Patient safety related incidents and daylight savings time transitions.

J Gen Intern Med 2021 04 26;36(4):1121. Epub 2021 Jan 26.

Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1007/s11606-021-06602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041957PMC
April 2021

Development of a Taxonomy for Medication-Related Patient Safety Events Related to Health Information Technology in Pediatrics.

Appl Clin Inform 2020 10 28;11(5):714-724. Epub 2020 Oct 28.

Division of Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States.

Background: Although electronic health records (EHRs) are designed to improve patient safety, they have been associated with serious patient harm. An agreed-upon and standard taxonomy for classifying health information technology (HIT) related patient safety events does not exist.

Objectives: We aimed to develop and evaluate a taxonomy for medication-related patient safety events associated with HIT and validate it using a set of events involving pediatric patients.

Methods: We performed a literature search to identify existing classifications for HIT-related safety events, which were assessed using real-world pediatric medication-related patient safety events extracted from two sources: patient safety event reporting system (ERS) reports and information technology help desk (HD) tickets. A team of clinical and patient safety experts used iterative tests of change and consensus building to converge on a single taxonomy. The final devised taxonomy was applied to pediatric medication-related events assess its characteristics, including interrater reliability and agreement.

Results: Literature review identified four existing classifications for HIT-related patient safety events, and one was iteratively adapted to converge on a singular taxonomy. Safety events relating to usability accounted for a greater proportion of ERS reports, compared with HD tickets (37 vs. 20%,  = 0.022). Conversely, events pertaining to incorrect configuration accounted for a greater proportion of HD tickets, compared with ERS reports (63 vs. 8%,  < 0.01). Interrater agreement (%) and reliability (kappa) were 87.8% and 0.688 for ERS reports and 73.6% and 0.556 for HD tickets, respectively.

Discussion: A standardized taxonomy for medication-related patient safety events related to HIT is presented. The taxonomy was validated using pediatric events. Further evaluation can assess whether the taxonomy is suitable for nonmedication-related events and those occurring in other patient populations.

Conclusion: Wider application of standardized taxonomies will allow for peer benchmarking and facilitate collaborative interinstitutional patient safety improvement efforts.
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http://dx.doi.org/10.1055/s-0040-1717084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593115PMC
October 2020

Increased Patient Safety-Related Incidents Following the Transition into Daylight Savings Time.

J Gen Intern Med 2021 01 12;36(1):51-54. Epub 2020 Aug 12.

Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.

Background: "Spring forward," the start of daylight savings time (DST), reduces sleep opportunity by an hour. Insufficient sleep in healthcare workers resulting from the spring forward time change could potentially result in an increase in medical errors.

Objective: We examined the change in reported patient safety-related incidents (SRIs), in the week following the transition into and out of DST over a period of 8 years.

Design: Observational study SETTING: A US-based large healthcare organization with sites across multiple states MEASUREMENTS: Voluntarily reported SRIs that occurred 7 days prior to and following the spring and fall time changes for years 2010-2017 were ascertained. SRIs likely resulting from human error were identified separately. The changes in the number of SRIs (either all SRIs or SRIs restricted to those likely resulting from human error) from the week before and after the time change (either spring or fall) were modeled using a negative binomial mixed model with a random effect to correct for non-independent observations in consecutive weeks.

Results: Over the 8-year period, we observed 4.2% (95% CI: - 1.1 to 9.7%; p = 0.12) and 8.8% (95% CI: - 2.5 to 21.5%; p = 0.13) increases in overall SRIs in the 7 days following DST when compared with 7 days prior for spring and fall, respectively. By restricting to SRIs likely resulting from human errors, we observed 18.7% (95% CI: 5.6 to 33.6%; p = 0.004) and 4.9% (95% CI: - 1.3 to 11.5%; p = 0.12) increases for spring and fall, respectively.

Conclusion: Policy makers and healthcare organizations should evaluate delayed start of shifts or other contingency measures to mitigate the increased risk of SRIs during transition to DST in spring.
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http://dx.doi.org/10.1007/s11606-020-06090-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859153PMC
January 2021

Impact of a Program to Improve Venous Thromboembolism Prophylaxis on Incidence of Thromboembolism and Bleeding Rates in Hospitalized Patients During Implementation of Programs to Improve Venous Thromboembolism Prophylaxis.

Mayo Clin Proc Innov Qual Outcomes 2020 Apr 17;4(2):159-169. Epub 2020 Feb 17.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.

Objective: To study the impact of multiphase quality improvement efforts to enhance appropriate use of chemical and mechanical venous thromboembolism (VTE) prophylaxis (VTEP) on the rate of hospital-acquired VTE and determine whether efforts have been associated with increased bleeding complications.

Patients And Methods: All adult inpatients discharged between January 1, 2005, and December 31, 2015, were included in the study. Retrospective interrupted time series analysis compared VTEP performance, VTE outcomes, and unintended consequences (derived from linked administrative and clinical data) across 5 improvement phases: baseline (January 1, 2005-December 31, 2006), paper order set phase (January 1, 2007-February 9, 2009), electronic order set phase (February 10, 2009-December 16, 2009), active reminder phase (December 17, 2009-May 31, 2012), and maintenance phase (June 1, 2012-September 30, 2015).

Results: Guideline VTEP plan adherence at the end of the study period (including documenting contraindications) reached 88.8% (654,138 of 736,384 patient days). Delivery of pharmacological VTEP increased from 43.9% (49,155 of 111,906 patients) to 60.8% (75,784 of 124,676 patients); delivery of mechanical or pharmacological VTEP increased less (65.0% [431,791 of 664,087 patient days] to 67.4% [496,625 of 736,384 patient days]). Mean VTE rates decreased from 4.6 per 1000 hospitalizations (21.7 VTEs per month) at baseline to 4.3 per 1000 hospitalizations (18.0 VTEs per month) during the maintenance phase (<.001). More than 97% of patients who had development of VTE (534 of 548) received VTEP, but 65.7% (360 of 548) experienced gaps of 1 or more days in VTEP delivery. Measured in-hospital bleeding rates were fairly consistent over the study (4.6% [5,198 of 111,906 patients] at baseline to 5.3% [6,662 of 124,676 patients] during the reminder phase). There was little change in rates of 7-day readmission with bleeding or VTE.

Conclusion: Our VTEP project improved guideline compliance, increased the proportion of patients receiving VTEP, and was associated with a decrease in VTE. Gaps in VTEP delivery occurred despite protocoled order sets and electronic feedback. Further improvements in VTE may require new approaches.
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http://dx.doi.org/10.1016/j.mayocpiqo.2019.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140013PMC
April 2020

Enhancing the patient and family experience during pediatric sleep studies.

J Clin Sleep Med 2020 07;16(7):1037-1043

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: Pediatric polysomnography can result in suboptimal patient and provider (physician and advanced practice provider) experiences. We embarked on a project aimed at increasing the proportion of maximal satisfaction survey scores by a minimum of 10% in 1 year without adding personnel or major expenses.

Methods: We used a Six Sigma framework, define, measure, analyze, improve, and control (DMAIC), to conduct our analysis. For measurement, we designed a project-specific survey that was given to caregivers of children who underwent PSG in February 2018 and repeated the survey after interventions in February 2019. Lean and Six Sigma quality improvement tools were used to define important processes that influence patient satisfaction, including: supplier, input, process, output, customer, and requirements (SIPOC-R); journey mapping; 1-2-4-All brainstorming; and views solicited from our center's Patient and Family Advisory Council. We analyzed the relationships between identified processes and outcomes using usual descriptive statistics. We prioritized interventions using a Kano model and a quality function deployment (QFD) technique to rank priorities for interventions. Multiple opportunities to improve patient and family satisfaction before, during, and after a pediatric polysomnography were identified. Many were simple, one-step interventions and were implemented simultaneously. For those that required substantial training and/or scheduling changes, pilots were performed and plan, do, study, act (PDSA) cycles were used to check effectiveness.

Results: After implementation, top box scores rose 20%, from 51% (n = 47) in 2018 to 71% (n = 50) in 2019.

Conclusions: Various quality improvement techniques employed in business, engineering, and manufacturing were used to identify and address areas of improvement in the pediatric polysomnography experience.
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http://dx.doi.org/10.5664/jcsm.8386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954068PMC
July 2020

Frequency and outcomes of primary central sleep apnea in a population-based study.

Sleep Med 2020 04 24;68:177-183. Epub 2019 Dec 24.

Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Primary central sleep apnea (PCSA) is believed to be rare and data regarding its prevalence and long-term outcomes are sparse. We used the Rochester Epidemiology Project (REP) resources to identify all Olmsted County, Minnesota, residents with an incident diagnosis of PCSA and their clinical outcomes.

Methods: We searched the REP database for all residents with polysomnography (PSG)-confirmed diagnoses of central sleep apnea (CSA) between 2007 and 2015. From these, we reviewed the PSGs and medical records to find those who had PCSA based upon accepted diagnostic criteria. Data based on detailed review of the medical records, including all clinical notes and tests were recorded for analysis.

Results: Of 650 patients identified with CSA, 25 (3.8%; 23 male) had PCSA, which was severe in most patients (n = 16, 64%). Of those, 23 (92%) patients were prescribed and 18/23 (78.2%) adherent to positive airway pressure therapy. Median duration of follow-up was 4.4 years (IQR:4.2). Four (16%) patients were subsequently diagnosed with cardiac arrhythmias, one (4%) with unstable angina, two (8%) with heart failure, five (20%) with mild cognitive impairment (MCI)/dementia and two (8%) with depression. Six (25%) patients died (median time to death = 5 years; IQR:4.8), three of whom had Lewy body dementia.

Conclusions: In this population-based study, PCSA was rare and when present, was severe in a majority of patients. The mortality rate was high. Most frequently observed disorders during follow-up were mild cognitive impairment (MCI)/dementia followed by cardiac arrhythmias; it is possible that these entities were present and not recognized prior to the diagnosis of PCSA.
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http://dx.doi.org/10.1016/j.sleep.2019.12.008DOI Listing
April 2020

Multisite validation of a simple electronic health record algorithm for identifying diagnosed obstructive sleep apnea.

J Clin Sleep Med 2020 02 13;16(2):175-183. Epub 2020 Jan 13.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.

Study Objectives: We examined the performance of a simple algorithm to accurately distinguish cases of diagnosed obstructive sleep apnea (OSA) and noncases using the electronic health record (EHR) across six health systems in the United States.

Methods: Retrospective analysis of EHR data was performed. The algorithm defined cases as individuals with ≥ 2 instances of specific International Classification of Diseases (ICD)-9 and/or ICD-10 diagnostic codes (327.20, 327.23, 327.29, 780.51, 780.53, 780.57, G4730, G4733 and G4739) related to sleep apnea on separate dates in their EHR. Noncases were defined by the absence of these codes. Using chart reviews on 120 cases and 100 noncases at each site (n = 1,320 total), positive predictive value (PPV) and negative predictive value (NPV) were calculated.

Results: The algorithm showed excellent performance across sites, with a PPV (95% confidence interval) of 97.1 (95.6, 98.2) and NPV of 95.5 (93.5, 97.0). Similar performance was seen at each site, with all NPV and PPV estimates ≥ 90% apart from a somewhat lower PPV of 87.5 (80.2, 92.8) at one site. A modified algorithm of ≥ 3 instances improved PPV to 94.9 (88.5, 98.3) at this site, but excluded an additional 18.3% of cases. Thus, performance may be further improved by requiring additional codes, but this reduces the number of determinate cases.

Conclusions: A simple EHR-based case-identification algorithm for diagnosed OSA showed excellent predictive characteristics in a multisite sample from the United States. Future analyses should be performed to understand the effect of undiagnosed disease in EHR-defined noncases. This algorithm has wide-ranging applications for EHR-based OSA research.
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http://dx.doi.org/10.5664/jcsm.8160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053021PMC
February 2020

Rationale, design, and development of SleepWell24: A smartphone application to promote adherence to positive airway pressure therapy among patients with obstructive sleep apnea.

Contemp Clin Trials 2020 02 14;89:105908. Epub 2019 Dec 14.

College of Health Solutions, Arizona State University, United States of America. Electronic address:

Background: Positive airway pressure (PAP) therapy is the gold standard treatment for obstructive sleep apnea (OSA), a chronic disorder that affects 6-13% of the adult population. However, adherence to PAP therapy is challenging, and current approaches to improve adherence have limited efficacy and scalability.

Methods/design: To promote PAP adherence, we developed SleepWell24, a multicomponent, evidence-based smartphone application that delivers objective biofeedback concerning PAP use and sleep/physical activity patterns via cloud-based PAP machine and wearable sensor data, and behavior change strategies and troubleshooting of PAP therapy interface use. This randomized controlled trial will evaluate the feasibility, acceptability, and initial efficacy of SleepWell24 compared to a usual care control condition during the first 60 days of PAP therapy among patients newly diagnosed with OSA.

Discussion: SleepWell24 is an innovative, multi-component behavior change intervention, designed as a self-management approach to addressing the psychosocial determinants of adherence to PAP therapy among new users. The results will guide lengthier future trials that assess numerous patient-centered and clinical outcomes.
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http://dx.doi.org/10.1016/j.cct.2019.105908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415005PMC
February 2020

Noninvasive volume-assured pressure support for chronic respiratory failure: a review.

Curr Opin Pulm Med 2019 11;25(6):570-577

Department of Pulmonary and Critical Care Medicine and the Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Purpose Of Review: Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure (CRF). Volume-assured pressure support (VAPS) is a mode of NIV that automatically adjusts inspiratory pressure in order to maintain a constant respiratory volume. We aim to discuss the role and application of VAPS in CRF.

Recent Findings: Recently published meta-analyses and reviews fail to demonstrate a significant difference in gas exchange, sleep, or quality-of-life improvement between VAPS and bilevel positive airway pressure (BPAP) in patients with CRF. A recent manuscript suggests that VAPS therapy in chronic obstructive pulmonary disease patients may reduce the number of exacerbations. It has been shown that with a protocol-driven approach BPAP and VAPS can both be successfully titrated during a single split-night polysomnography.

Summary: VAPS is as effective as other modes of NIV at improving ventilation and sleep in CRF. The potential advantage is a more consistent ventilatory support through daytime-nighttime variations and progression of disease over time. However, the impact on long-term outcomes, such as survival, has not been studied.
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http://dx.doi.org/10.1097/MCP.0000000000000605DOI Listing
November 2019

Prevalence and Sources of Errors in Positive Airway Pressure Therapy Provisioning.

J Clin Sleep Med 2019 05 15;15(5):697-704. Epub 2019 May 15.

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: The prevalence and mechanism of medication errors have been well characterized in the literature. However, no prior studies have investigated the frequency and characteristics of errors in the positive airway pressure (PAP) therapy provisioning process when treating patients with sleep-disordered breathing. Just as medication errors may result in unwanted outcomes, it might be anticipated that errors in providing PAP to patients might lead to suboptimal outcomes. Our study seeks to examine the characteristics and frequency of PAP provisioning errors.

Methods: This was a retrospective analysis of a cohort of patients in whom sleep-disordered breathing had been diagnosed and subsequently PAP therapy was prescribed. At a 90-day return visit, the PAP therapy the patient was receiving was compared with the intended therapy. Discrepancies were categorized as either prescribing errors (the prescription did not match the intended modality or settings), or setup errors (the modality or settings did not match the prescription).

Results: The overall PAP provisioning error rate was 8%, with errors most commonly occurring during the set-up process. In univariate analysis, insurance type ( = .003), treatment modality ( = .002), and device brand ( = .05) were associated with error and remained significant in multivariate analysis (model fit = .002). Compliance, residual AHI, and difference in Epworth Sleepiness Scale were not affected by the presence of error.

Conclusions: PAP provisioning errors are common and might contribute to poor treatment outcomes. Errors might be reduced by standardizing terminology across devices, standardizing prescription forms to improve clarity, and by enhanced quality assurance at durable medical equipment suppliers.
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http://dx.doi.org/10.5664/jcsm.7752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510673PMC
May 2019

The Effect of Patient-Facing Applications on Positive Airway Pressure Therapy Adherence: A Systematic Review.

J Clin Sleep Med 2019 05 15;15(5):769-777. Epub 2019 May 15.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: Many patients struggle with adherence to positive airway pressure (PAP) therapy for sleep apnea. In this systematic review we examined the effect that patient-facing applications (PFA)-web-based applications that interact directly with the patient-have on PAP adherence.

Methods: A comprehensive search of PubMed, CINAHL, MEDLINE, and SCOPUS databases was performed. We looked for studies where: (1) patients were adults with sleep apnea initiating PAP therapy for the first time; (2) the intervention was a PFA that incorporated individual PAP use data; (3) the comparison was usual and/or telemedicine care, and (4) outcomes of objective PAP adherence data were recorded.

Results: Seven studies were identified (two randomized trials, one prospective cohort trial, four retrospective cohort studies). Cumulatively the studies enrolled 304,328 patients, with individual enrollment ranging between 61 and 172,678 patients. Six studies showed that PFA use was associated with using PAP for significantly more hours per night (range 0.7-1.3 hours more). PFA cohorts used PAP a greater proportion of nights and had a lower rate of mask leak. There was no difference in apnea-hypopnea index and self-reported measures of symptoms between study groups.

Conclusions: PFA use was associated with improved adherence to PAP therapy. Although this conclusion is based on only two small trials and predominantly observational studies and therefore should be tested in large prospective trials, the PAFs are inexpensive, do not draw on health care resources, and show promise in improving PAP therapy for OSA.
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http://dx.doi.org/10.5664/jcsm.7772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510681PMC
May 2019

Effect of Varying Definitions of Hypopnea on the Diagnosis and Clinical Outcomes of Sleep-Disordered Breathing: A Systematic Review and Meta-Analysis.

J Clin Sleep Med 2019 05 15;15(5):687-696. Epub 2019 May 15.

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: Various criteria have been used for scoring hypopneas, leading to difficulties when comparing results in clinical and research settings. We conducted a systematic review and meta-analysis to assess the effect of different hypopnea definitions on the diagnosis, severity, and clinical implications of sleep-disordered breathing (SDB).

Methods: Ovid MEDLINE, Embase, and Scopus databases were queried for English-language publications from inception through March 7, 2017. Studies that directly compared various hypopnea definitions were eligible. The hierarchical summary receiver operating characteristic model was used to jointly estimate diagnostic performance for comparisons between criteria.

Results: The initial search yielded 2,828 abstracts; 28 met inclusion criteria. After reviewing reference lists and expert review, five additional articles were identified. Most of the studies were cross-sectional or retrospective in nature. Eleven studies compared 2007 recommended criteria with 2012 criteria; 6 of these (evaluating 6,628 patients) were suitable for inclusion in the meta-analysis. Using the 2012 definition (≥ 3% desaturation or arousal) as the reference standard, the 2007 definition (≥ 4% desaturation) showed a sensitivity of 82.7% (95% confidence interval 0.72-0.90) and specificity of 93.2% (95% confidence interval 0.82-0.98). Although 2007 criteria were found to be associated with prevalent cardiovascular (CV) disease and increased risk of CV death, the 2012 criteria appeared to correspond better with intermediate CV risk markers based on two abstracts.

Conclusions: As expected, 2012 hypopnea scoring criteria resulted in a greater prevalence and severity of SDB. Data regarding the effect of varying hypopnea definitions on clinical outcomes, quality of life, health care costs, and mortality rates are limited.

Commentary: A commentary on this article appears in this issue on page 683.
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http://dx.doi.org/10.5664/jcsm.7750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510679PMC
May 2019

Workplace Interventions to Promote Sleep Health and an Alert, Healthy Workforce.

J Clin Sleep Med 2019 04 15;15(4):649-657. Epub 2019 Apr 15.

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: The purpose of this review is to synthesize the published literature that addresses employer-initiated interventions to improve the sleep of workers and in turn improve health, productivity, absenteeism, and other outcomes that have been associated with sleep disorders or sleep deficiency.

Methods: We conducted a systematic search and a selective narrative review of publications in PubMed from 1966 to December 2017. We extracted study characteristics, including the workers' professions, workplace settings and shift work, and workplace interventions focused on worker sleep. Because of the high degree of heterogeneity in design and outcomes, we conducted a narrative review.

Results: We identified 219 publications. After restriction to publications with studies of workplace interventions that evaluated the outcomes of sleep duration or quality, we focused on 47 articles. An additional 13 articles were accepted in the pearling process. Most studies employed non-randomized or controlled pretest and posttest designs and self-reported measures of sleep. The most common workplace interventions were educational programs stressing sleep hygiene or fatigue management. Other interventions included timed napping before or after work, urging increased daytime activity levels, modifying workplace environmental characteristics such as lighting, and screening, and referral for sleep disorders treatment. Overall, most reports indicated that employer efforts to encourage improved sleep hygiene and healthier habits result in improvements in sleep duration, sleep quality, and self-reported sleepiness complaints.

Conclusions: These studies suggest employer-sponsored efforts can improve sleep and sleep-related outcomes. The existing evidence, although weak, suggests efforts by employers to encourage better sleep habits and general fitness result in self-reported improvements in sleep-related outcomes, and may be associated with reduced absenteeism and better overall quality of life. Candidate workplace strategies to promote sleep health are provided.
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http://dx.doi.org/10.5664/jcsm.7734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457507PMC
April 2019

Effects of Adaptive Servoventilation Therapy for Central Sleep Apnea on Health Care Utilization and Mortality: A Population-Based Study.

J Clin Sleep Med 2019 01 15;15(1):119-128. Epub 2019 Jan 15.

Center for Sleep Medicine, Mayo Clinic, Minnesota.

Study Objectives: Adaptive servoventilation (ASV) is the suggested treatment for many forms of central sleep apnea (CSA). We aimed to evaluate the impact of treating CSA with ASV on health care utilization.

Methods: In this population-based study using the Rochester Epidemiology Project database, we identified patients over a 9-year period who were diagnosed with CSA (n = 1,237), commenced ASV therapy, and had ≥ 1 month of clinical data before and after ASV initiation. The rates of hospitalizations, emergency department visits (EDV), outpatient visits (OPV) and medications prescribed per year (mean ± standard deviation) in the 2 years pre-ASV and post-ASV initiation were compared.

Results: We found 309 patients (68.0 ± 14.6 years, 80.3% male, apnea-hypopnea index 41.6 ± 26.5 events/h, 78% with cardiovascular comorbidities, 34% with heart failure) who met inclusion criteria; 65% used ASV ≥ 4 h/night on ≥ 70% nights in their first month. The overall 2-year mortality rate was 9.4% and CSA secondary to cardiac cause was a significant risk factor for mortality (hazard ratio 1.81, 95% CI 1.09-3.01, = .02). Comparing pre-ASV and post-ASV initiation, there was no change in the rate of hospitalization (0.72 ± 1.63 versus 0.79 ± 1.44, = .46), EDV (1.19 ± 2.18 versus 1.26 ± 2.08, = .54), OPV (31.59 ± 112.42 versus 13.60 ± 17.36, = .22), or number of prescribed medications (6.68 ± 2.0 versus 5.31 ± 5.86, = .06). No differences in these outcomes emerged after accounting for adherence to ASV, CSA subtype and comorbidities via multiple regression analysis (all > .05).

Conclusions: Our cohort of patients with CSA was quite ill and the use of ASV was not associated with a change in health care utilization.
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http://dx.doi.org/10.5664/jcsm.7584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329537PMC
January 2019

Practical Implementation of a Single-Night Split-Titration Protocol With BPAP-ST and AVAPS in Patients With Neuromuscular Disease.

J Clin Sleep Med 2018 12 15;14(12):2031-2035. Epub 2018 Dec 15.

Center for Sleep Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: At the sleep laboratory, noninvasive positive pressure ventilation titration protocols in patients with neuromuscular disease (NMD) are based on standard pressure cycle devices in a spontaneous/timed mode (BPAP-ST). Experience integrating protocols on average volume-assured pressure support (AVAPS) mode is limited, prompting us to develop a practical single-night titration protocol that provides information to assist clinicians and patients as they decide between BPAP-ST and AVAPS modes.

Methods: We implemented a sequential titration protocol of BPAP-ST followed by AVAPS during a single-night polysomnography study in patients with NMD and reported polysomnographic and clinical metrics.

Results: There were 27 patients who completed the protocol: 14 (52%) were male with median and interquartile range (IQR) 64 (59 to 70) years of age and body mass index of 29.6 (25.6-32) kg/m. They had median (IQR) maximal percent predicted inspiratory and expiratory pressures, and percent vital capacity of 33 (24 to 54), 34 (22 to 47) and 60 (47 to 74), respectively. At final titration of each device, average tidal volume and nadir non-rapid eye movement sleep oxyhemoglobin saturation (SpO) were higher and respiratory rate/tidal volume, transcutaneous CO, and arousal index were lower on AVAPS ( < .05) in comparison with BPAP-ST. Full face mask was used in 23 patients (85%). None of the other ventilatory or sleep parameters differed significantly between BPAP-ST and AVAPS ( > .05) sessions.

Conclusions: A practical single-night split-titration protocol with BPAP-ST and AVAPS can successfully be implemented in patients with NMD, assisting clinicians and patients with the decision on initial treatment modalities and settings.
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http://dx.doi.org/10.5664/jcsm.7530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287715PMC
December 2018

Medical Cannabis for Obstructive Sleep Apnea: Premature and Potentially Harmful.

Mayo Clin Proc 2018 06;93(6):689-692

Mayo Clinic Center for Sleep Medicine, Mayo Clinic, Rochester, MN; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2018.04.011DOI Listing
June 2018

Sleep and Nocturnal Gastroesophageal Reflux: An Update.

Chest 2018 10 31;154(4):963-971. Epub 2018 May 31.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease.
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http://dx.doi.org/10.1016/j.chest.2018.05.030DOI Listing
October 2018

Position Paper for the Treatment of Nightmare Disorder in Adults: An American Academy of Sleep Medicine Position Paper.

J Clin Sleep Med 2018 06 15;14(6):1041-1055. Epub 2018 Jun 15.

American Academy of Sleep Medicine, Darien, Illinois.

Introduction: Nightmare disorder affects approximately 4% of adults, occurring in isolation or as part of other disorders such as posttraumatic stress disorder (PTSD), and can significantly impair quality of life. This paper provides the American Academy of Sleep Medicine (AASM) position regarding various treatments of nightmare disorder in adults.

Methods: A literature search was performed based upon the keywords and MeSH terms from the Best Practice Guide for the Treatment of Nightmare Disorder in Adults that was published in 2010 by the AASM. The search used the date range March 2009 to August of 2017, and sought to find available evidence pertaining to the use of behavioral, psychological, and pharmacologic therapies for the treatment of nightmares. A task force developed position statements based on a thorough review of these studies and their clinical expertise. The AASM Board of Directors approved the final position statements.

Determination Of Position: Positions of "recommended" and "not recommended" indicate that a treatment option is determined to be clearly useful or ineffective/harmful for most patients, respectively, based on a qualitative assessment of the available evidence and clinical judgement of the task force. Positions of "may be used" indicate that the evidence or expert consensus is less clear, either in favor or against the use of a treatment option. The interventions listed below are in alphabetical order within the position statements rather than clinical preference: this is not meant to be instructive of the order in which interventions should be used.

Position Statements: The following therapy is recommended for the treatment of PTSD-associated nightmares and nightmare disorder: image rehearsal therapy. The following therapies may be used for the treatment of PTSD-associated nightmares: cognitive behavioral therapy; cognitive behavioral therapy for insomnia; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy; the atypical antipsychotics olanzapine, risperidone and aripiprazole; clonidine; cyproheptadine; fluvoxamine; gabapentin; nabilone; phenelzine; prazosin; topiramate; trazodone; and tricyclic antidepressants. The following therapies may be used for the treatment of nightmare disorder: cognitive behavioral therapy; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method; nitrazepam; prazosin; and triazolam. The following are not recommended for the treatment of nightmare disorder: clonazepam and venlafaxine. The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, accessible treatment options, and resources.
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http://dx.doi.org/10.5664/jcsm.7178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991964PMC
June 2018

Sleep Duration and Hypertension: Analysis of > 700,000 Adults by Age and Sex.

J Clin Sleep Med 2018 06 15;14(6):1031-1039. Epub 2018 Jun 15.

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: The objective of this study was to evaluate the cross-sectional relationship between sleep duration and hypertension in a large, nationally-representative dataset that spans 10 years. This analysis may provide detailed information with high resolution about how sleep duration is related to hypertension and how this differs by demographic group.

Methods: Data were aggregated from the 2013 Behavioral Risk Factor Surveillance System (n = 433,386) and the combined 2007-2016 National Health Interview Surveys (n = 295,331). These data were collected by the Centers for Disease Control and Prevention from nationally-representative samples. Surveys were combined, and survey-specific weights were used in all analyses. Sleep duration was assessed with the item, "On average, how many hours of sleep do you get in a 24-hour period?" in both surveys. Hypertension was assessed as self-reported history. Covariates were assessed identically in both datasets and included, age (in 5-year groupings), sex, race/ethnicity, and employment status.

Results: In adjusted analyses, compared to 7 hours, increased risk of hypertension was seen among those sleeping ≤ 4 hours (odds ratio [OR] = 1.86, < .0005), 5 hours (OR = 1.56, < .0005), 6 hours (OR = 1.27, < .0005), 9 hours (OR = 1.19, < .0005), and ≥ 10 hours (OR = 1.41, < .0005). When stratified by age, sex, and race/ethnicity groups, short sleep was associated with increased risk for all age groups < 70 years, and long sleep (≥ 10 hours only) was associated with risk for all except < 24 years and > 74 years. Findings for short sleep were relatively consistent across all race/ethnicities, although findings for long sleep were less pronounced among Black/African-American and Other/Multiracial groups. A significant sleep by 3-way sleep × age × sex interaction ( < .0005) suggests that the relationship depends on both age and sex. For both men and women, the OR of having hypertension associated with short sleep decreases with increasing age, but there is a higher association between short sleep and hypertension for women, throughout the adult lifespan.

Conclusions: Both short and long sleep duration are associated with increased hypertension risk across most age groups. The influence of covariates is stronger upon long sleep relationships. Relationships with short sleep were stronger among younger adults and women.
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http://dx.doi.org/10.5664/jcsm.7176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991947PMC
June 2018

Analyses of the Complexity of Patients Undergoing Attended Polysomnography in the Era of Home Sleep Apnea Tests.

J Clin Sleep Med 2018 04 15;14(4):631-639. Epub 2018 Apr 15.

Mayo Clinic Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: Health care complexity includes dimensions of patient comorbidity and the level of services needed to meet patient demands. Home sleep apnea tests (HSAT) are increasingly used to test medically uncomplicated patients suspected of having moderate to severe obstructive sleep apnea (OSA). Patients with significant comorbidities or other sleep disorders are not candidates for HSAT and require attended in-center polysomnography. We hypothesized that this trend would result in increasingly complex patients being studied in sleep centers.

Methods: Our study had two parts. To ascertain trends in sleep patient comorbidity, we used administrative diagnostic codes from patients undergoing polysomnography at the Mayo Clinic Center for Sleep Medicine from 2005 to June 2015 to calculate the Charlson and the Elixhauser comorbidity indices. We measured the level of services provided in two ways: (1) in a subset of patients from the past 2 months of 2015, we evaluated correlation of these morbidity indices with an internally developed Polysomnogram Clinical Index (PSGCI) rating anticipated patient care needs from 0 to 3 and (2) we measured the sleep study complexity based on polysomnography protocol design.

Results: In 43,780 patients studied from 2005 to June 2015, the Charlson index increased from a mean of 1.38 to 1.88 (3.1% per year, < .001) and the mean Elixhauser index increased from 2.61 to 3.35 (2.5% per year, < .001). Both comorbidity indices were significantly higher at the highest (Level 3) level of the PSGCI ( < .001), and sleep study complexity increased over time.

Conclusions: The complexity of patients undergoing attended polysomnography has increased by 28% to 36% over the past decade as measured by validated comorbidity indices, and these indices correlate with the complexity of rendered care during polysomnography. These findings have implications for increasing requirements for staffing, monitoring capabilities, and facility design of future sleep centers.

Commentary: A commentary on this article appears in this issue on page 499.
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http://dx.doi.org/10.5664/jcsm.7060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886441PMC
April 2018

Knowledge Gaps in the Perioperative Management of Adults with Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome. An Official American Thoracic Society Workshop Report.

Ann Am Thorac Soc 2018 02;15(2):117-126

The purpose of this workshop was to identify knowledge gaps in the perioperative management of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). A single-day meeting was held at the American Thoracic Society Conference in May, 2016, with representation from many specialties, including anesthesiology, perioperative medicine, sleep, and respiratory medicine. Further research is urgently needed as we look to improve health outcomes for these patients and reduce health care costs. There is currently insufficient evidence to guide screening and optimization of OSA and OHS in the perioperative setting to achieve these objectives. Patients who are at greatest risk of respiratory or cardiac complications related to OSA and OHS are not well defined, and the effectiveness of monitoring and other interventions remains to be determined. Centers involved in sleep research need to develop collaborative networks to allow multicenter studies to address the knowledge gaps identified below.
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http://dx.doi.org/10.1513/AnnalsATS.201711-888WSDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850745PMC
February 2018

The National Healthy Sleep Awareness Project Sleep Health Surveillance Questionnaire as an Obstructive Sleep Apnea Surveillance Tool.

J Clin Sleep Med 2017 Sep 15;13(9):1067-1074. Epub 2017 Sep 15.

Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota.

Study Objectives: To validate the previously published National Healthy Sleep Awareness Project (NHSAP) Surveillance and Epidemiology Workgroup questionnaire for ability to determine risk for moderate to severe obstructive sleep apnea (OSA).

Methods: The NHSAP sleep questions, part of the next Behavioral Risk Factor Surveillance System (BRFSS), were constructed to mimic elements of the STOP sleep apnea questionnaire, and included number of days with sleep disruption and unintentional dozing and a history of snoring and apneas. The responses to four sleep questions from the BRFSS were collected from 352 adults undergoing in-laboratory polysomnography at Mayo Clinic, Rochester, Minnesota. Demographic and clinical information, including sex, age, body mass index (BMI), and presence of hypertension, which will be available in other parts of the complete BRFSS, were obtained by chart review. Univariate and logistic regression analyses were performed, and values of < .05 were considered to be statistically significant.

Results: Fifty-five percent of subjects were men and 45% were women with a median age of 58 years and BMI 32.2 kg/m. Sixty percent had no or mild OSA, and 40% had moderate to severe OSA. No single question was superior in screening for moderate to severe OSA, although a history of snoring and witnessed apneas was more likely to predict moderate to severe OSA. Male sex, age ≥ 50 years, BMI ≥ 30 kg/m, presence of hypertension, and a history of snoring and witnessed apneas were the most highly weighted factors in predicting moderate to severe OSA. When each variable was dichotomized to a single point, a cutoff of 5 points significantly predicted a high risk of moderate to severe OSA with an odds ratio of 3.87 (2.39-6.27).

Conclusions: Although many variables were positively associated with the apnea-hypopnea index, no single factor was superior in predicting moderate to severe OSA. Male sex, increased age, higher BMI, hypertension, and a history of snoring and witnessed apneas are the most highly predictive of moderate to severe OSA. Combined use of the NHSAP questionnaire and demographic and clinical characteristics could be considered for screening for moderate to severe OSA.
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http://dx.doi.org/10.5664/jcsm.6724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566462PMC
September 2017
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