Sleep Apnea

Implementing Peer-Driven Care to patients with sleep apnea (PCORI; DI-2018C2-13161) Sairam Parthasarathy, MD

Treatment adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) was improved after experienced trained patients (called “peer buddies”) helped patients with OSA who recently received CPAP therapy better use the CPAP machine. CPAP usage at six months was better in the treatment group than in the group that received written materials and educational DVDs/videos. Patients who received support from peer buddies experienced greater satisfaction for CPAP support than did patients in the control group, who received conventional education. Moreover, patients rated their care coordination as better, were less sleepy, and had lower blood pressure if they were sleepy or hypertensive when they began the study participation.

Our project tackles an important barrier in the field of sleep medicine. OSA affects 7% to 12% of the US population and is an independent risk factor for several clinical consequences, such as systemic hypertension, cardiovascular disease, stroke, reduced health-related quality of life, increased all-cause mortality, and motor vehicle accidents due to sleepiness. In a recent large study, treatment of OSA with CPAP therapy improved quality of life and mood, but the effect on mortality was limited by poor CPAP adherence. The readiness and willingness to change and sustain such changes are present, as evidenced by the health plan expressing willingness to pay for these peer buddies’ time. Such sustainability makes our study ready for implementation efforts.

Monitoring and Peer Support to Improve Treatment Adherence and Outcomes in Patients with Overlap Chronic Obstructive Pulmonary Disease and Sleep Apnea via a Large PCORnet Collaboration (O2VERLAP); PPRND-1507-31666 (Sairam Parthasarathy, MD; Site-PI)

Chronic obstructive pulmonary disease, or COPD, and obstructive sleep apnea are long-term health problems that affect millions of people in the United States. Both health problems can make breathing hard and limit oxygen to the body. About 10 to 15 percent of people with COPD also have sleep apnea. People with both health problems have an increased risk of death. They also go to the hospital more often than people with either health problem alone. Continuous positive airway pressure, or CPAP, therapy is one effective way to treat COPD and sleep apnea together. CPAP machines use mild air pressure to keep the airways open and help people breathe while sleeping. However, patients don’t always use CPAP therapy the right way. In this study, the research team is testing two ways to help patients use CPAP therapy. The team is comparing how well each way improves CPAP use, sleep quality, and daytime sleepiness in patients with COPD and sleep apnea. Our University of Arizona researchers are collaborating with researchers in University of California San Diego, American Sleep Apnea Association, and the COPD Foundation.

Predictive Analytics and Peer-Driven Intervention for Guideline-based Care for Sleep Apnea (NIH-NHLBI R56HL138377) Sairam Parthasarathy, MD

Obstructive sleep apnea (OSA) affects 12% of the US population and is associated with cardiovascular disease, reduced health-related quality of life (HR-QOL), increased all-cause mortality. However, nearly 80% of patients with OSA remain undiagnosed [QUALITY GAP #1]. Moreover, adequate adherence to continuous positive airway pressure (CPAP) therapy can improve HR-QOL and mood but the beneficial effects on cardiovascular outcomes are limited by poor CPAP adherence with nearly 54% of patients being non-adherent to CPAP therapy [QUALITY GAP #2]. The American Academy of Sleep Medicine (AASM) released evidence- based clinical practice guidelines and quality metrics for the improved diagnosis and treatment of OSA, but these have not been implemented in underserved populations. The overarching aim of this proposal is to institute a multi-level strategy with interventions aimed at both providers and patients in order to improve guideline based care for OSA in populations with health disparities. Specifically, in order to address the under- diagnosis of OSA, we will implement an electronic health record (EHR) based predictive analytics system that is similar to recently implemented early warning system that triggers guideline-based treatment of sepsis in hospitalized patients. The proposed EHR-based alert with reflex order sets will enable primary care physicians (PCPs) to adopt the AASM guidelines for diagnosing OSA. In approximately 220,000 patients we have found that lower neighborhood income is associated with lower CPAP adherence. Considering the time and access- related barriers in the PCP office, we believe that such health disparities in CPAP adherence need to be addressed by culturally-competent peer educators with OSA serving as “peer-buddies”. In a recent study we found that CPAP adherence can be improved by a peer-driven intervention through an interactive voice response system (PDI-IVR). Whether PDI-IVR can improve adherence in underserved populations in low resource clinics is unclear. Specific Aim #1: To test an EHR-based tool to alert primary care physicians of the potential for OSA in order to improve the diagnosis of OSA in low resource clinics. Specific Aim #2: To test a peer-driven intervention with interactive voice response (PDI-IVR) system to improve treatment adherence in populations with health disparities. Specific Aim #3: To evaluate the dissemination and implementation of a multi-level intervention strategy aimed at improving the diagnosis and treatment of OSA in populations with health disparities. We are proposing a RCT that recruits 102 providers, 362 patients, and 50 experienced peer-buddies in an underserved population with an excess burden of sleep disorders (Medicaid and dual- eligible Medicare beneficiaries in Pima county, Arizona) that is aimed at addressing the health disparities in the diagnosis and treatment of OSA. We will use a systems-level intervention (EHR-based tool) that targets providers and a patient-level educational intervention (PDI-IVR system) that targets patients in order to increase delivery of guideline-based care to populations with health disparities and promote health equity.

Neurocognitive Impairment in Children with Congenital Heart Disease and Sleep-Disordered Breathing (AASM Foundation 150-JF-16; Daniel Combs, MD)

he goal of the project is to determine how SDB contributes to the observed neurocognitive impairment and health-related QOL in children with CHD, as well as to define factors that influence patient and caregiver preferences for treatment. Results so far suggest that the presence of SDB is associated with a 15 point lower IQ in children with CHD, and Dr. Combs expects the research could demonstrate a treatable cause of neurocognitive impairment in children with CHD.

Impact of Low Flow Nocturnal Oxygen Therapy On Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apneal (LOFT-HF). (Parthasarathy; Site-PI)

This is a multi-center, randomized, double-blind, sham-controlled outcomes trial that will rigorously evaluate the long-term effects of nocturnal oxygen supplementation on mortality, morbidity, hospitalizations, functional status, and quality of life in patients with heart failure and central sleep apnea. Central sleep apnea (CSA), prevalent in approximately 40% of patients with heart failure with reduced ejection fraction (HFrEF), predicts high rates of morbidity, hospitalizations, and mortality. Adverse effects are thought to be attributable to hypoxemia, central nervous system arousal, and sympathetic nervous system activation resulting from episodic breathing disturbances and oxyhemoglobin desaturation. Until recently, the recommended treatment for CSA with HFrEF was adaptive servo-ventilation (ASV). A recent multi-national trial, however, identified an adverse effect of ASV on mortality, leaving a void in therapeutic options for patients with these co-morbid disorders. Although low flow nocturnal oxygen, which provides a physiologically sound intervention for blunting hypoxemia-associated physiological stresses and sympathetic activation, and improves short-term intermediate outcomes in patients with CSA and HFrEF, no large scale study yet has examined its long term impact on clinically important outcomes. We have assembled a team of leaders in cardiology, sleep medicine and clinical trials to conduct a pragmatic trial designed to test the hypothesis that nocturnal oxygen therapy (NOXT) in patients with CSA and HFrEF will reduce mortality and unplanned hospitalizations for worsening HF. Secondary endpoints evaluate other measures of morbidity and mortality, functional status, exercise capacity, quality of life, mood, and sleep quality. Using a double-blinded, randomized design, we will screen 2,450 patients with home sleep studies, estimating that 35% (n=858) will meet study eligibility criteria for CSA. Participants will be randomized to NOXT or sham-NOXT and undergo standardized assessments including a 6 minute walk test, complete validated questionnaires, and will be followed for study outcomes for as long as 4.5 years. Oxygen use and oxygen saturation levels will be centrally monitored using cloud-based software. Primary outcomes will be assessed using a time to first event analysis, and secondarily as recurrent event rates. Highly efficient methods for data capture and monitoring and project management will be deployed. Novel physiological markers of ventilation during sleep will be derived to identify responsive subgroups. This rigorous yet practical design will provide pivotal trial data needed to identify the role of a potentially beneficial and acceptable therapy which has yet to be tested on a large scale in a population with high morbidity and mortality, for a condition where there is no current evidence-based treatment. The sleep assessments and interventions are practically designed with the objective of facilitating their rapid uptake and use by the cardiology and sleep communities. This Data Coordinating Center application is to provide the study comprehensive, responsive, and innovative data management and study coordination services, biostatistical analysis, rigorous adjudication of study outcomes, and centralized sleep analysis and oxygen monitoring to ensure that the study meets its milestones.

Effect of Servo-Ventilation on CO2 regulation and Heart Rate Variability  (Sairam Parthasarathy, MD; PI)

This aim of this study is to compare the effects of various servo-ventilation devices on QTc interval.

Medications for obstructive sleep apnea to improve cognition in children with down syndrome (MOSAIC DS). (Daniel Combs, MD; PI)

This is a randomized, double blind, cross-over study of the combination of atomoxetine and oxybutynin (ato-oxy) in children with DS and OSA documented by polysomnography (PSG). Participants will receive high dose ato-oxy for four weeks as well as low dose ato-oxy for four weeks in random order. During the high dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine nightly for one week. Atomoxetine dose will then be increased to 1.2 mg/kg/day (max 80 mg). During the low dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine. Dosing of the study treatment will occur approximately 30 minutes prior to bedtime. Participants who withdraw from the study will not be replaced.

Study participants will undergo eligibility screening that will include an initial screening to determine whether non- PSG enrollment criteria are met, followed by a 1 night in-lab PSG and health-related quality of life assessment for participants who qualify based on non-PSG criteria. For participants who are eligible and enroll in the study, the screening PSG night will serve as the baseline measure for apnea hypopnea index (AHI) and other PSG endpoints. On the final night of dosing for both high dose ato-oxy and low-dose ato-oxy, participants will return for inpatient PSG and health-related quality of life assessment. The primary efficacy endpoint is the change in obstructive AHI from baseline (high dose ato-oxy vs. low dose ato-oxy).

Cardiorespiratory Interactions during Noninvasive Ventilation. (Salma Patel, MD; AASM Foundation)

Obstructive sleep apnea (OSA) is a prevalent condition and has been associated with increased mortality. It is unknown whether OSA-related changes on markers of ventricular repolarization are responsible for mediating the relationship between OSA and death. A retrospective analysis of existing sleep study databases will be performed to review baseline markers of ventricular repolarization in patients with OSA and evaluate the impact of apneas/hypopneas and all modes of noninvasive ventilation on markers of ventricular repolarization and mortality.