Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health-related quality of life. Data from two 12-week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10-item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36-Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10-item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36-Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3-0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10-item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self-reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health-related quality of life than objectively assessed sleepiness.

Determination of thresholds for minimally important difference and clinically important response on the functional outcomes of sleep questionnaire short version in adults with narcolepsy or obstructive sleep apnea.

PURPOSE: This study estimated thresholds for clinically important responses and minimally important differences for two indicators of improvement for the 10-item version of the functional outcomes of sleep questionnaire (FOSQ-10). METHODS: Participants with excessive daytime sleepiness with narcolepsy or obstructive sleep apnea received 12 weeks of solriamfetol treatment. Participants completed the FOSQ-10 and other patient-reported outcome measures, including the single-item patient global impression of change (PGI-C) assessment. Clinicians completed the single-item clinician global impression of change (CGI-C) for each participant. Data from the two studies were analyzed separately, both without regard to treatment assignment. In total, 690 participants (47% female, mean age 48 years, 77% Caucasian, 91% from North America) were enrolled. Two clinically important changes, defined as a minimally important difference and a clinically important response, were determined using distribution and anchor-based analyses. A receiver operating characteristic analysis was used to determine the optimal FOSQ-10 change threshold. RESULTS: Spearman correlations between change in FOSQ-10 scores and PGI-C and CGI-C were - 0.57 and - 0.49 for participants with narcolepsy and - 0.42 and - 0.37 for participants with obstructive sleep apnea. Receiver operating characteristic analysis suggested minimally important difference and clinically important response estimates of 1.7 and 2.5 and 1.8 and 2.2 points in narcolepsy and obstructive sleep apnea, respectively. CONCLUSIONS: Minimally important difference and clinically important response estimates for the FOSQ-10 for adults with excessive daytime sleepiness in narcolepsy or obstructive sleep apnea will be helpful for interpreting changes over time and defining a clinical responder. CLINICALTRIALS. GOV IDENTIFIERS: NCT02348593 (first submitted January 15, 2015) and NCT02348606 (first submitted January 15, 2015).

A French update on the Self-Efficacy Measure for Sleep Apnea (SEMSA) to assess continuous positive airway pressure (CPAP) use.

PURPOSE: The Self-Efficacy Measure for Sleep Apnea (SEMSA) is a 26-item self-questionnaire composed of three factors: risk perception of obstructive sleep apnea syndrome (OSAS), benefit of continuous positive airway pressure (CPAP), and self-efficacy (the confidence to engage in CPAP use). It is used to evaluate health beliefs about OSAS and CPAP in order to optimize CPAP use. The purpose of this study was to design and validate a French version of the SEMSA. METHODS: A forward-backward translation of the SEMSA was performed. Subjects with OSAS treated by CPAP and followed by our sleep clinic were invited to complete the questionnaire. The psychometric properties of the French SEMSA version were analyzed in terms of its construct validity (with confirmatory factor analysis, CFA), internal structural validity (Cronbach's alpha coefficient), and external validity (Pearson's correlation between SEMSA score and duration of CPAP use). RESULTS: Two hundred eighty-eight subjects filled in the questionnaire. The mean age was 63.16 ± 12.73 years. The number of years since the beginning of CPAP treatment was 6.58 ± 6.03 years. The mean CPAP use duration was 6.19 ± 2.03 h/night. CFA was unsatisfactory (RMSEA = 0.066 and CFI = 0.88). The exploratory factor analysis revealed a fourth factor named "cardiovascular risk" factor. Cronbach's alpha coefficient was 0.886. The correlation between the "self-efficacy" factor and the duration of CPAP use was significant (r = 0.26, p ≤ 0.001). CONCLUSIONS: The French version of the SEMSA is a psychometrically acceptable self-report questionnaire for measuring health beliefs and behavior in French patients with OSAS treated with CPAP. Such translation and validation should lead to the adoption of validated psychosocial methods for improving CPAP use.

A Tailored Intervention for PAP Adherence: The SCIP-PA Trial.

OBJECTIVE/BACKGROUND: Positive airway pressure (PAP) is highly efficacious treatment but nonadherence is prevalent with little improvement over the last 15 years. Tailored interventions show promise for promoting adherence to other treatments. The study objective was to examine feasibility and acceptability of a tailored intervention to promote PAP adherence. PARTICIPANTS: The convenience sample met inclusion criteria: newly diagnosed OSA; treatment-naïve; ≥ 18 years. EXCLUSION CRITERIA: previous obstructive sleep apnea (OSA) diagnosis and treatment; new psychiatric diagnosis; use of oxygen/bilevel PAP; secondary sleep disorder. Adults (n = 118) were randomized to tailored intervention (TI; n = 61) or usual care (UC; n = 57); application of a priori exclusion criteria resulted in 30 participants per assignment who were middle-aged (51.3 ± 11.1 years) adults (70% male) with severe OSA (apnea hypopnea index [AHI], 35.9 ± 25.2). METHODS: Randomized, double-blind, single-site pilot controlled trial. A multiphased tailored intervention targeting social cognitive perceptions of OSA-PAP treatment was delivered at four intervals. Descriptive analysis, group differences, and self-efficacy change scores by t-test, and thematic analysis of acceptability data are reported. RESULTS: One-week PAP use among TI was 35 min greater than UC condition (p = 0.20; Cohen's d = 0.336). Treatment use decreased at 1 month and 3 months (NS). Per-protocol delivery of face-to-face intervention delivery was 100% but lower for telephone intervention delivery. Personalized approach was valued by participants. CONCLUSIONS: A tailored intervention approach is acceptable to participants and feasibly implemented in a clinical sleep center setting. The intervention effect size at 1 week is consistent with other educational PAP adherence interventions but was not sustained; further pilot testing is warranted to address pilot RCT limitations.

Update on Research and Practices in Major Sleep Disorders: Part I. Obstructive Sleep Apnea Syndrome.

PURPOSE: The purpose of this first of two review articles providing an update on sleep disorders was to examine the pathophysiology, epidemiology, and treatment of obstructive sleep apnea (OSA). OSA is a common sleep disorder whose prevalence is similar to asthma. As with other sleep disorders, OSA has a broad impact on individuals, affecting their daily behaviors, cognitive abilities, and performance, and putting them at increased risk for accidents, mood disorders, cancer, cardiovascular disease, and hypertension. Thus, early recognition and management, much of which can be implemented by nurses, can reduce health and accident risks and improve daily functioning. METHODS: This narrative review utilized medical databases such as PubMed to identify relevant English language original and systematic review articles predominantly from peer-reviewed journals from 2012 to 2018. However, as background, findings from classic articles prior to 2012 were also included. CLINICAL RELEVANCE: OSA is a common condition with considerable impact on daily functioning and potential for accidents and serious comorbidities such as hypertension, cardiovascular disease, diabetes, and depressed mood. The impairments and comorbidities associated with OSA can be reduced through early detection, encouraging treatment, providing education about sleep and OSA, and, importantly, promoting adherence to the predominant therapy, positive airway pressure.

Update on Research and Practices in Major Sleep Disorders: Part II-Insomnia, Willis-Ekbom Disease (Restless Leg Syndrome), and Narcolepsy.

PURPOSE: This review (Part II of a series on sleep disorders) presents an update of the characteristics, epidemiology, assessment, and latest management of insomnia, restless legs syndrome (Willis-Ekbom disease; RLS/WED), and narcolepsy. Insomnia, the most common sleep disorder and most prevalent of all psychological health disorders, is a problem of difficulty initiating and maintaining sleep and early morning awakenings. RLS/WED is characterized by a crawling sensation or urge to move the legs in the evening and nighttime. Narcolepsy is a sleep disorder that commonly results in chronic daytime sleepiness and cataplexy. Nonpharmacological management, which includes education, cognitive behavioral therapy, and complementary therapy, is used as primary or adjunctive to pharmacotherapy for the treatment of these disorders. METHODS: This narrative review utilized medical databases such as PubMed to identify relevant English-language original and systematic review articles predominantly from peer-reviewed journals from 2012 to 2019. However, as background, findings from classic articles prior to 2012 were also included. CLINICAL RELEVANCE: Assessment of sleep problems, excessive sleepiness, and difficulty performing activities or being productive should be routine in the care of all patients. Utilization of behavioral interventions, including cognitive behavioral therapy, in addition to education and sleep hygiene, can promote sleep quality. Management of insomnia, RLS/WED, and narcolepsy should include helping patients adjust to treatment, managing cataplexy triggers in narcolepsy, and initiating strategies to live with chronic illness to improve quality of life.

Criteria for gauging response to sodium oxybate for narcolepsy.

Our objective was to define responder criteria using an anchor-based approach for frequency of cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo-controlled, double-blind, multicentre 4- and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analysed using receiver operator characteristics analysis. The percentage change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared with Clinical Global Impression of Change ratings, used as the anchor to define true response. Participants (n = 336) were 39% male, 89% white, with a mean age of 41.5 (15.3) years, reporting a median of 20.5 cataplexy attacks per week and a mean Epworth Sleepiness score of 17.5 at baseline. A majority (51%) were Much Improved or Very Much Improved based on Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%) supported response definition thresholds of 46% and 12%, respectively. Classification using either response definition agreed with the anchor for approximately 71% of participants. Cataplexy response definition was more sensitive (cataplexy = 0.77, Epworth Sleepiness Scale = 0.69), while sleepiness was more specific (cataplexy = 0.66, Epworth Sleepiness Scale = 0.75). Both responder definitions showed a dose-response relationship with sodium oxybate, demonstrating their validity using an external criterion. Weekly cataplexy attacks and Epworth Sleepiness Scale can be used to help document clinical response to narcolepsy treatment using criteria of 46% and 12% reductions, respectively.

Brain white matter changes in CPAP-treated obstructive sleep apnea patients with residual sleepiness.

PURPOSE: To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence. MATERIALS AND METHODS: Twenty-nine male patients (30-55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of the magnetic resonance imaging (MRI) scan. Based on the PVT results, the patients were divided into a nonsleepy group (lapses ≤5) and a sleepy group (lapses >5). DTI was performed at 3T, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1 ), and radial diffusivity (λ23 ) between the two groups. RESULTS: A higher MD (P < 0.05) was observed in the sleepy group than the nonsleepy group in the whole-brain TBSS analysis in the WM. The increased MD (17.8% of the fiber tracts; P < 0.05) was caused primarily by an elevated λ23 . Axial diffusivity (λ1 ) exhibited no significant difference (P > 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, P < 0.05). CONCLUSION: Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes. Evidence level: 1 J. MAGN. RESON. IMAGING 2017;45:1371-1378.

A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea.

PURPOSE: Our aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA. METHODS: Data were obtained from an education program for enhancing CPAP adherence. Men who were newly diagnosed of OSA and CPAP therapy naïve were recruited in a tertiary teaching hospital. RESULTS: Self-reported quality of life [Functional Outcomes of Sleep Questionnaire], daytime sleepiness [Epworth Sleepiness Scale (ESS)], and negative emotion symptoms [depression, anxiety, stress scale] were assessed before and after CPAP treatment at 1-year assessment. Seventy-three men were included in the data analysis, with a mean ± SD age of 52 ± 10 years, body mass index of 29.0 ± 5.2 kg/m(2), ESS of 9.5 ± 5.6, and median [interquartile range(IR)] apnea and hypopnea index of 31 (21, 56) events/h. The median (IR) CPAP daily usage was 4.3(0, 6.1) h/day. From the path analysis, CPAP therapy was shown to improve intimate relationship directly (ß = 0.185) and indirectly (ß = 0.050) by reducing daytime sleepiness and increasing activity level. However, negative emotion symptoms were not the mediators between CPAP adherence and the intimate relationship. CONCLUSIONS: CPAP therapy with good adherence is related directly and indirectly to a better intimate relationship with bed partner in men with OSA. It was possibly attributed to reduced daytime sleepiness and increased activity level.

Impaired sustained attention and lapses are present in patients with mild obstructive sleep apnea.

BACKGROUND: Severe obstructive sleep apnea (OSA) directly affects the quality of life, mood, and sustained attention of individuals, but it has not yet been established in the literature, if these changes also affect patients with mild OSA. The purpose of this study was to investigate such negative effects on the parameters described above. METHODS: A controlled study was held at the Universidade Federal de Sao Paulo, Department of Psychobiology. Thirty-nine mild OSA patients and 25 controls were included. Volunteers could be of both genders with body mass index (BMI) ≤35 kg/m(2) and age between 18 and 65 years. Both groups were subjected to full-night polysomnography (PSG), the subjective assessment of mood (Beck Inventory of Anxiety and Depression), Functional Outcomes of Sleep Questionnaire (FOSQ), and the psychomotor vigilance task (PVT) five times during the day. We considered mild OSA patients those with apnea-hypopnea index (AHI) score between 5 and 15. The control group included subjects with AHI scores <5, respiratory disturbance index (RDI) scores ≤5, arousal index values ≤15, and Epworth Sleepiness Scale (ESS) values ≤9. RESULTS: Mild OSA patients were older and more obese than the controls. After adjusting for age, BMI, and schooling years, there was an increased number of total lapses (3.90 ± 4.16 and 2.43 ± 5.55, p = 0.004). CONCLUSIONS: Patients with mild OSA showed increased sustained attention lapses compared with normal subjects.

Validation of the Chinese Version of the Functional Outcomes of Sleep Questionnaire-10 in Pregnant Women.

We evaluated the psychometric properties of a Mandarin Chinese version of the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10) in pregnant women. A total of 228 first-trimester pregnant women participated in the study, which was conducted in an outpatient obstetric clinic at a medical center in Taipei, Taiwan. The Chinese version of the FOSQ-10 demonstrated satisfactory internal consistency (Cronbach alpha = .85), adequate corrected item-total correlations (from .40 to .67), and acceptable test-retest reliability over 7 days (ICC = .73). Construct validity was supported by exploratory factor analysis showing a one-factor structure with item loadings between .49 and .77. Significant associations with the Medical Outcomes Study Short-Form Health Survey 12 version 2 and Pittsburgh Sleep Quality Index supported criterion-related and convergent validity. Significant differences in the Chinese version of the FOSQ-10 total scores were found between women with clinically significant daytime sleepiness and those without, suggesting adequate discriminant validity. Ceiling effects were observed for all items, but no floor or ceiling effects were found for total scores. Findings suggest that the Chinese version of the FOSQ-10 is a valid and reliable instrument to identify important effects of sleep-related impairment in Chinese women during pregnancy. Further testing is needed in more diverse pregnant women, such as women with complicated pregnancies and those with sleep disorders. © 2016 Wiley Periodicals, Inc.

Daytime sleepiness in renal transplant recipients is associated with immunosuppressive non-adherence: a cross-sectional, multi-center study.

BACKGROUND: The aims of this study were to determine the prevalence of immunosuppressive non-adherence (NA) in renal transplant patients and describe whether the degree of daytime sleepiness (DS) and depressive symptomatology are associated with immunosuppressive NA. METHODS: Using a cross-sectional design, 926 home-dwelling renal transplant recipients who were transplanted at one of three Swiss transplant centers provided data by self-report. The Basel Assessment of Adherence Scale for immunosuppressive was used to measure the following: taking, timing, and overall NA to immunosuppressive medication. DS was assessed with the Epworth Sleepiness Scale (ESS) (cut-off ≥6 for DS) and the Swiss Transplant Cohort Study DS item (cut-off ≥4 for DS), and depressive symptomatology was assessed with the Depression, Anxiety, and Stress Scale (cut-off>10). An ordinal logistical regression model was applied for statistical analysis. RESULTS: The prevalence of the ESS-DS was 51%. NA for taking, timing, and the median overall NA level assessed by 0-100% visual analog scale (VAS) was 16%, 42%, and 0%, respectively. Based on the multivariate analysis, DS was significantly associated (p < 0.001) with taking (1.08 [1.04-1.13]), timing (1.07 [1.03-1.10]), and overall NA (1.09 [1.05-1.13]). Very similar results were found for the Swiss Transplant Cohort Study DS item. CONCLUSION: DS is associated with immunosuppressive medication NA in renal transplant recipients. Admittedly, the association's strength is limited.

An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults.

BACKGROUND: Continuous positive airway pressure (CPAP) is considered the treatment of choice for obstructive sleep apnea (OSA), and studies have shown that there is a correlation between patient adherence and treatment outcomes. Newer CPAP machines can track adherence, hours of use, mask leak, and residual apnea-hypopnea index (AHI). Such data provide a strong platform to examine OSA outcomes in a chronic disease management model. However, there are no standards for capturing CPAP adherence data, scoring flow signals, or measuring mask leak, or for how clinicians should use these data. METHODS: American Thoracic Society (ATS) committee members were invited, based on their expertise in OSA and CPAP monitoring. Their conclusions were based on both empirical evidence identified by a comprehensive literature review and clinical experience. RESULTS: CPAP usage can be reliably determined from CPAP tracking systems, but the residual events (apnea/hypopnea) and leak data are not as easy to interpret as CPAP usage and the definitions of these parameters differ among CPAP manufacturers. Nonetheless, ends of the spectrum (very high or low values for residual events or mask leak) appear to be clinically meaningful. CONCLUSIONS: Providers need to understand how to interpret CPAP adherence tracking data. CPAP tracking systems are able to reliably track CPAP adherence. Nomenclature on the CPAP adherence tracking reports needs to be standardized between manufacturers and AHIFlow should be used to describe residual events. Studies should be performed examining the usefulness of the CPAP tracking systems and how these systems affect OSA outcomes.

An official American Thoracic Society research statement: comparative effectiveness research in pulmonary, critical care, and sleep medicine.

BACKGROUND: Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patient-centered outcomes research (PCOR). PURPOSE: To summarize key aspects of CER definitions and provide examples highlighting the complementary nature of efficacy and CER studies in pulmonary, critical care, and sleep medicine. METHODS: An ad hoc working group of the American Thoracic Society with experience in clinical trials, health services research, quality improvement, and behavioral sciences in pulmonary, critical care, and sleep medicine was convened. The group used an iterative consensus process, including a review by American Thoracic Society committees and assemblies. RESULTS: The traditional efficacy paradigm relies on clinical trials with high internal validity to evaluate interventions in narrowly defined populations and in research settings. Efficacy studies address the question, "Can it work in optimal conditions?" The CER paradigm employs a wide range of study designs to understand the effects of interventions in clinical settings. CER studies address the question, "Does it work in practice?" The results of efficacy and CER studies may or may not agree. CER incorporates many attributes of outcomes research and health services research, while placing greater emphasis on meeting the expressed needs of nonresearcher stakeholders (e.g., patients, clinicians, and others). CONCLUSIONS: CER complements traditional efficacy research by placing greater emphasis on the effects of interventions in practice, and developing evidence to address the needs of the many stakeholders involved in health care decisions. Stakeholder engagement is an important component of CER.

Risk assessment for CPAP nonadherence in adults with newly diagnosed obstructive sleep apnea: preliminary testing of the Index for Nonadherence to PAP (I-NAP).

PURPOSE: Identification of risk for continuous positive airway pressure therapy (CPAP) nonadherence prior to home treatment is an opportunity to deliver targeted adherence interventions. Study objectives included the following: (1) test a risk screening questionnaire to prospectively identify CPAP nonadherence risk among adults with newly diagnosed obstructive sleep apnea (OSA), (2) reduce the questionnaire to a minimum item set that effectively identifies 1-month CPAP nonadherence, and (3) examine the diagnostic utility of the screening index. METHODS: A prospective, longitudinal study at two clinical sleep centers in the USA included adults with newly diagnosed OSA (n=97; AHI≥5 events/h) by polysomnogram (PSG) consecutively recruited to participate. After baseline participant and OSA characteristics were collected, a risk screening questionnaire was administered immediately following CPAP titration polysomnogram. One-month objective CPAP use was collected. RESULTS: Predominantly, white (87%), males (55%), and females (45%) with obesity (BMI 38.3 kg/m2; SD 9.3) and severe OSA (AHI 36.8; SD 19.7) were included. One-month CPAP use was 4.25 h/night (SD 2.35). Nineteen questionnaire items (I-NAP) reliably identified nonadherers defined at <4 h/night CPAP use (Wald X2[8]=34.67, p<0.0001) with ROC AUC 0.83 (95% CI 0.74-0.91). Optimal score cut point for the I-NAP screening questionnaire were determined to maximize sensitivity (87%) while maintaining specificity>60% (63%). CONCLUSION: A risk screening questionnaire employed immediately after titration PSG may reliably identify CPAP nonadherers and permit the delivery of targeted interventions to prevent or reduce nonadherence. This novel approach may enhance cost-effectiveness of care and permit appropriate allocation of resources for CPAP adherence.

Psychometric Properties of the Turkish Version of Self-Efficacy Measure for Sleep Apnea (SEMSA) Instrument.

BACKGROUND: Determining the self-efficacy perceptions of obstructive sleep apnea (OSA) patients has a key role in health care practices. With further evaluation, the Self-Efficacy Measure for Sleep Apnea (SEMSA) could serve as a useful scale to develop specific interventions to increase self-efficacy in patients with OSA during the acceptance and maintenance of continuous positive airway pressure (CPAP) therapy. OBJECTIVE: The aim of this study is to translate the SEMSA into Turkish and to evaluate the psychometric properties of the translation. METHODS: This cross-sectional study was carried out with a sample of patients recently diagnosed with CPAP-naïve OSA. Linguistic and content validity of the scale were evaluated, while exploratory factor analysis and 2-level confirmatory factor analysis were used for validity. Internal consistency and test-retest methods were used in reliability analyses. RESULTS: The mean (SD) age of the patients with OSA was 51.36 (11.29), and 68% were male. The item factor loads obtained as a result of the confirmatory factor analysis ranged from 0.44 to 0.94, confirming the three-factor structure of the instrument. The Cronbach's α coefficient of the scale was found to be 0.90. Measurements made within the scope of test-retest analysis were found to be related and consistent results were obtained in the intervening time (P < .01). CONCLUSIONS: In this study, the Turkish version of SEMSA was found to be a valid and reliable tool and it could be used to evaluate the adherence-related cognition in Turkish patients with OSA on CPAP therapy.

Continuous positive airway pressure treatment of sleepy patients with milder obstructive sleep apnea: results of the CPAP Apnea Trial North American Program (CATNAP) randomized clinical trial.

RATIONALE: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. OBJECTIVES: To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. METHODS: Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. MEASUREMENTS AND MAIN RESULTS: The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. The adjusted mean change in the Total score after the first 8-week intervention was 0.89 for the active group (n = 113) and -0.06 for the placebo group (n = 110) (P = 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 ± 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. CONCLUSIONS: Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea.

Self-reported sleep disturbances in renal transplant recipients.

BACKGROUND: Poor sleep quality (SQ) and daytime sleepiness (DS) are common in renal transplant (RTx) recipients; however, related data are rare. This study describes the prevalence and frequency of self-reported sleep disturbances in RTx recipients. METHODS: This cross-sectional study included 249 RTx recipients transplanted at three Swiss transplant centers. All had reported poor SQ and / or DS in a previous study. With the Survey of Sleep (SOS) self-report questionnaire, we screened for sleep and health habits, sleep history, main sleep problems and sleep-related disturbances. To determine a basis for preliminary sleep diagnoses according to the International Classification of Sleep Disorders (ICSD), 164 subjects were interviewed (48 in person, 116 via telephone and 85 refused). Descriptive statistics were used to analyze the data and to determine the frequencies and prevalences of specific sleep disorders. RESULTS: The sample had a mean age of 59.1 ± 11.6 years (60.2% male); mean time since Tx was 11.1 ± 7.0 years. The most frequent sleep problem was difficulty staying asleep (49.4%), followed by problems falling asleep (32.1%). The most prevalent sleep disturbance was the need to urinate (62.9%), and 27% reported reduced daytime functionality. Interview data showed that most suffered from the first ICSD category: insomnias. CONCLUSION: Though often disregarded in RTx recipients, sleep is an essential factor of wellbeing. Our findings show high prevalences and incidences of insomnias, with negative impacts on daytime functionality. This indicates a need for further research on the clinical consequences of sleep disturbances and the benefits of insomnia treatment in RTx recipients.