Objective adherence to dental device versus positive airway pressure treatment in adults with obstructive sleep apnea.

Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.

Predictors of sleepiness in obstructive sleep apnoea at baseline and after 6†months of continuous positive airway pressure therapy.

We evaluated factors associated with subjective and objective sleepiness at baseline and after 6 months of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA).We analysed data from the Apnoea Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and after 6 months of CPAP therapy were recorded.Excessive sleepiness (ESS score >10) was present in 543 (49.1%) participants. Younger age, presence of depression and higher apnoea-hypopnoea index were all associated with higher ESS scores and lower MSL. Randomisation to the CPAP group was associated with lower odds of sleepiness at 6 months. The prevalence of sleepiness was significantly lower in those using CPAP >4 h·night-1versus using CPAP ≤4 h·night-1 Among those with good CPAP adherence, those with ESS >10 at baseline had significantly higher odds (OR 8.2, p<0.001) of persistent subjective sleepiness.Lower average nightly CPAP use and presence of sleepiness at baseline were independently associated with excessive subjective and objective sleepiness after 6 months of CPAP therapy.

Impact of continuous positive airway pressure (CPAP) on quality of life in patients with obstructive sleep apnea (OSA).

Obstructive sleep apnea is a chronic illness with increasing prevalence. In addition to associated cardiovascular comorbidities, obstructive sleep apnea syndrome has been linked to poor quality of life, occupational accidents, and motor vehicle crashes secondary to excessive daytime sleepiness. Although continuous positive airway pressure is the gold standard for sleep apnea treatment, its effects on quality of life are not well defined. In the current study we investigated the effects of treatment on quality of life using the data from the Apnea Positive Pressure Long-term Efficacy Study (APPLES), a randomized controlled trial of continuous positive airway pressure (CPAP) versus sham CPAP. The Calgary Sleep Apnea Quality of Life Index (SAQLI) was used to assess quality of life. Overall we found no significant improvement in quality of life among sleep apnea patients after CPAP treatment. However, after stratifying by OSA severity, it was found that long-term improvement in quality of life might occur with the use of CPAP in people with severe and possibly moderate sleep apnea, and no demonstrable improvement in quality of life was noted among participants with mild obstructive sleep apnea.

Strategies for de-identification and anonymization of electronic health record data for use in multicenter research studies.

BACKGROUND: De-identification and anonymization are strategies that are used to remove patient identifiers in electronic health record data. The use of these strategies in multicenter research studies is paramount in importance, given the need to share electronic health record data across multiple environments and institutions while safeguarding patient privacy. METHODS: Systematic literature search using keywords of de-identify, deidentify, de-identification, deidentification, anonymize, anonymization, data scrubbing, and text scrubbing. Search was conducted up to June 30, 2011 and involved 6 different common literature databases. A total of 1798 prospective citations were identified, and 94 full-text articles met the criteria for review and the corresponding articles were obtained. Search results were supplemented by review of 26 additional full-text articles; a total of 120 full-text articles were reviewed. RESULTS: A final sample of 45 articles met inclusion criteria for review and discussion. Articles were grouped into text, images, and biological sample categories. For text-based strategies, the approaches were segregated into heuristic, lexical, and pattern-based systems versus statistical learning-based systems. For images, approaches that de-identified photographic facial images and magnetic resonance image data were described. For biological samples, approaches that managed the identifiers linked with these samples were discussed, particularly with respect to meeting the anonymization requirements needed for Institutional Review Board exemption under the Common Rule. CONCLUSIONS: Current de-identification strategies have their limitations, and statistical learning-based systems have distinct advantages over other approaches for the de-identification of free text. True anonymization is challenging, and further work is needed in the areas of de-identification of datasets and protection of genetic information.

Impact of Randomization, Clinic Visits, and Medical and Psychiatric Cormorbidities on Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea.

STUDY OBJECTIVES: To evaluate factors associated with continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES) cohort. METHODS: The data from a prospective 6-mo multicenter randomized controlled trial with 558 subjects randomized to active CPAP and 547 to sham CPAP were analyzed to assess adherence to CPAP during first 2 mo (early period) and during months 5-6 (late period). RESULTS: Participants randomized to active CPAP had higher hours of nightly adherence compared to the sham CPAP group at both 2 (4.9 ± 2.0 h versus 4.07 ± 2.14 h, p < 0.001) and 6 mo (4.70 ± 2.08 h versus 3.41 ± 2.19 h, p < 0.001). Those assigned to sham CPAP were more likely to correctly identify their treatment group (70.0% versus 55.2%, p < 0.001). Irrespective of treatment group assignment, those who believed they were receiving active CPAP had higher hours of adherence than those who thought they were in the sham CPAP group at both 2 mo (4.91 ± 2.01 versus 4.17 ± 2.17, p < 0.001) and 6 mo (4.65 ± 2.10 versus 3.65 ± 2.22, p < 0.001). Among those randomized to active CPAP, older age was significantly related to CPAP use > 4 h per night. Presence of cardiovascular disorders was associated with higher hours of CPAP use, whereas presence of anxiety was associated with a trend toward lower hours of CPAP use. Presence of nasal congestion was associated with a decrease in mean daily CPAP use between the early and the late adherence period. The adherence during the week prior to a clinic visit was higher than the average adherence during the 2-mo period prior to the visit. CONCLUSIONS: Randomization to active therapy, belief that one is in the active treatment group, older age, and possibly presence of cardiovascular disorders are positively linked to CPAP adherence. Nasal congestion and anxiety are negatively associated with CPAP adherence. CPAP nightly usage increases as clinic visits approach.

Restless legs syndrome symptoms in primary care: a prevalence study.

BACKGROUND: There are relatively few studies on the prevalence of restless legs syndrome (RLS) in the general population, even fewer that used diagnostic questions covering all 4 essential diagnostic criteria defining the RLS symptom complex, and none that have reported on the 2 RLS phenotypes for patients seen by family physicians. METHODS: To determine the prevalence of the symptom complex, diagnostic for RLS in a primary care patient population, a prospective population-based single-center study was performed. Every adult patient presenting for care in a small rural primary care practice with mostly white patients was surveyed for a 1-year period using a validated RLS diagnostic questionnaire. RESULTS: A total of 2099 patients completed the questionnaire. Analysis revealed that 24.0% of these patients were positive for all 4 of the essential symptoms used to make the diagnosis of RLS and 15.3% reported these symptoms at least weekly. In addition, the RLS symptom complex was reported significantly more often by women than men and, as a whole, patients reporting the RLS symptoms were significantly older than patients without symptoms. The prevalence of symptoms increased with age until about 60 years and then showed a steady decrease thereafter. Further, early-onset RLS was significantly more common in women than men. CONCLUSIONS: A high prevalence of RLS symptoms was observed in this primary care population. This finding supports the need for heightened awareness in both the medical community and general population regarding this disorder, which can often be effectively treated within the primary care practice.

SMART DOCS: a new patient-centered outcomes and coordinated-care management approach for the future practice of sleep medicine.

ABSTRACT: The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control. CLINICAL TRIALS NUMBER: http://www.clinicaltrials.gov, NCT02037438.

Symptom-Based Prevalence of Sleep Disorders in an Adult Primary Care Population.

The prevalence of sleep disorders in a primary care physician practice in Moscow, Idaho, was studied between February 7, 1997, and February 6, 1998. This primary care clinic visit population was surveyed for this 1-year period. Every patient above the age of 18 years who visited the Moscow Clinic in this time period was either approached by our on-site researcher during the patient's clinic visit or contacted via mail. Out of a total of 1249 adult patients who met with our on-site researcher during their clinic visit, 962 (77.0%) completed questionnaires and were interviewed for symptoms of sleep disorders. An additional 292 patients completed mailed questionnaires, resulting in a total of 1254 participants in the study. The percentages of patients in our sample reporting symptoms of the following sleep disorders were insomnia (32.3%), obstructive sleep apnea syndrome (23.6%), and restless legs syndrome (29.3%). This study demonstrates the need for heightened awareness and subsequent diagnosis and treatment of sleep disorders in the primary care population.

The COMET Sleep Research Platform.

INTRODUCTION: The Comparative Outcomes Management with Electronic Data Technology (COMET) platform is extensible and designed for facilitating multicenter electronic clinical research. BACKGROUND: Our research goals were the following: (1) to conduct a comparative effectiveness trial (CET) for two obstructive sleep apnea treatments-positive airway pressure versus oral appliance therapy; and (2) to establish a new electronic network infrastructure that would support this study and other clinical research studies. DISCUSSION: The COMET platform was created to satisfy the needs of CET with a focus on creating a platform that provides comprehensive toolsets, multisite collaboration, and end-to-end data management. The platform also provides medical researchers the ability to visualize and interpret data using business intelligence (BI) tools. CONCLUSION: COMET is a research platform that is scalable and extensible, and which, in a future version, can accommodate big data sets and enable efficient and effective research across multiple studies and medical specialties. The COMET platform components were designed for an eventual move to a cloud computing infrastructure that enhances sustainability, overall cost effectiveness, and return on investment.

Impact of treatment with continuous positive airway pressure (CPAP) on weight in obstructive sleep apnea.

STUDY OBJECTIVE: To determine the impact of continuous positive airway pressure (CPAP) on weight change in persons with obstructive sleep apnea (OSA). DESIGN SETTING AND PARTICIPANTS: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blinded sham-controlled multicenter clinical trial conducted at 5 sites in the United States. Of 1,105 participants with an apnea hypopnea index ≥ 10 events/ hour initially randomized, 812 had body weight measured at baseline and after 6 months of study. INTERVENTION: CPAP or Sham CPAP. MEASUREMENTS: Body weight, height, hours of CPAP or Sham CPAP use, Epworth Sleepiness Scale score. RESULTS: Participants randomized to CPAP gained 0.35 ± 5.01 kg, whereas those on Sham CPAP lost 0.70 ± 4.03 kg (mean ± SD, p = 0.001). Amount of weight gain with CPAP was related to hours of device adherence, with each hour per night of use predicting a 0.42 kg increase in weight. This association was not noted in the Sham CPAP group. CPAP participants who used their device ≥ 4 h per night on ≥ 70% of nights gained the most weight over 6 months in comparison to non-adherent CPAP participants (1.0 ± 5.3 vs. -0.3 ± 5.0 kg, p = 0.014). CONCLUSIONS: OSA patients using CPAP may gain a modest amount of weight with the greatest weight gain found in those most compliant with CPAP. COMMENTARY: A commentary on this article appears in this issue on page 995. CITATION: Quan SF; Budhiraja R; Clarke DP; Goodwin JL; Gottlieb DJ; Nichols DA; Simon RD; Smith TW; Walsh JK; Kushida CA. Impact of treatment with continuous positive airway pressure (CPAP) on weight in obstructive sleep apnea.

A method for estimating normative distributions for study-specific populations of clinical trials.

For any particular psychological instrument, published normative distributions have been derived in one to at most a few specific "reference" populations. Here a method is provided for estimating a normative distribution pertinent to the specific population being evaluated in a randomized clinical trial. Normative quantiles are obtained using quantile regression, a method chosen for its flexibility in that no assumptions are made about the parametric form (e.g., Gaussian) of the normative distribution to be estimated. Outcome is regressed on disease severity for the τth quantile using that sample of consented participants who were not randomized because they fell below the trial's disease severity entry criterion. The τth quantile of the normative distribution is then estimated by the intercept of this fitted regression function, which corresponds to severity of zero. Additional covariates that explain variation in outcome may be included to permit adjustment for shifts in their distributions between the randomized and non-randomized samples. The method is illustrated using data on a depression instrument (GRID Hamilton Rating Scale for Depression) and a neurocognitive instrument (CogScreen Pathfinder Number) from a multicenter clinical trial in sleep apnea patients.

Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES).

STUDY OBJECTIVE: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). DESIGN, SETTING, AND PARTICIPANTS: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. INTERVENTION: Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) RESULTS: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. CONCLUSIONS: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. CLINICAL TRIAL INFORMATION: Registered at clinicaltrials.gov. Identifier: NCT00051363. CITATION: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

The association between obstructive sleep apnea and neurocognitive performance--the Apnea Positive Pressure Long-term Efficacy Study (APPLES).

STUDY OBJECTIVES: To determine associations between obstructive sleep apnea (OSA) and neurocognitive performance in a large cohort of adults. STUDY DESIGN: Cross-sectional analyses of polysomnographic and neurocognitive data from 1204 adult participants with a clinical diagnosis of obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES), assessed at baseline before randomization to either continuous positive airway pressure (CPAP) or sham CPAP. MEASUREMENTS: Sleep and respiratory indices obtained by laboratory polysomnography and several measures of neurocognitive performance. RESULTS: Weak correlations were found for both the apnea hypopnea index (AHI) and several indices of oxygen desaturation and neurocognitive performance in unadjusted analyses. After adjustment for level of education, ethnicity, and gender, there was no association between the AHI and neurocognitive performance. However, severity of oxygen desaturation was weakly associated with worse neurocognitive performance on some measures of intelligence, attention, and processing speed. CONCLUSIONS: The impact of OSA on neurocognitive performance is small for many individuals with this condition and is most related to the severity of hypoxemia.

The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures.

STUDY OBJECTIVE: To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea. DESIGN: Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy. SETTING: Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. PATIENTS OR PARTICIPANTS: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers. INTERVENTIONS: Active versus sham (subtherapeutic) CPAP. MEASUREMENTS AND RESULTS: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life. CONCLUSIONS: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.