Association of Anxiety and Depression in Obstructive Sleep Apnea Patients: A Systematic Review and Meta-Analysis.

Background: Obstructive sleep apnea (OSA) has been associated with mental disorders, but the strength of this association is unknown. The aim of our study was to investigate the association among OSA, depression, and anxiety in adults and to quantitatively summarize the results. Methods: A literature search in Medline, PubMed, PsycInfo, Scopus, and Web of Science was conducted. Seventy-three articles were selected for study. Results: The pooled prevalence of depressive and anxious symptoms in OSA patients was 35% (95% CI, 28-41%) and 32% (95% CI, 22-42%), respectively. Conclusions: The association between OSA, anxiety, and depression indicates the value of an early diagnosis and personalized treatment of OSA to improve mental disorders conditioning compliance to therapy. These conditions share a probably bidirectional relationship.

Recommendations for the implementation of distress screening programs in cancer centers: report from the American Psychosocial Oncology Society (APOS), Association of Oncology Social Work (AOSW), and Oncology Nursing Society (ONS) joint task force.

In 2015, the American College of Surgeons (ACoS) Commission on Cancer will require cancer centers to implement screening programs for psychosocial distress as a new criterion for accreditation. A joint task force from the American Psychosocial Oncology Society, the Association of Oncology Social Work, and the Oncology Nursing Society developed consensus-based recommendations to guide the implementation of this requirement. In this review, the authors provide recommendations regarding each of the 6 components necessary to meet the ACoS standard: 1) inclusion of psychosocial representation on the cancer committee, 2) timing of screening, 3) method/mode of screening, 4) tools for screening, 5) assessment and referral, and 6) documentation.

Association between cancer stigma and depression among cancer survivors: a nationwide survey in Korea.

OBJECTIVE: Cancer patients are more likely to experience depression than the general population. This study aims to evaluate the possible association between cancer stigma and depression among cancer patients. METHODS: As a part of the Korean government's program to develop comprehensive supportive care, we conducted a nationwide survey in 2010 at the National Cancer Center and in nine regional cancer centers across Korea. Cancer stigma was assessed by using a set of 12 questions grouped in three domains-impossibility of recovery, stereotypes of cancer patients, and experience of social discrimination. Depression was measured by using the Hospital Anxiety and Depression Scale. RESULTS: A total of 466 cancer patients were included in the study. Over 30% of the cancer survivors had negative attitudes toward cancer and held stereotypical views of themselves: about 10% of the participants experienced social discrimination due to cancer, and 24.5% reported clinically significant depressive symptoms. Patients who had or experienced cancer stigma were 2.5 times more likely to have depression than patients with positive attitudes. CONCLUSIONS: Regardless of highly developed medical science and increased survivorship, cancer survivors had cancer stigmas, and it was significantly associated with depression. IMPACT: Our findings emphasize the need for medical societies and health professionals to pay more attention to cancer stigma that patients are likely to experience during treatment.

Clinic-based depression screening in lung cancer patients using the PHQ-2 and PHQ-9 depression questionnaires: a pilot study.

OBJECTIVES: This study aims to validate the ability to perform depression screening with the patient health questionnaire (PHQ)-2 and PHQ-9 depression modules in a busy, outpatient practice, and to evaluate the prevalence of depression among lung cancer outpatients at our institution. METHODS: In 2010, 64 patients in a thoracic malignancy clinic completed the Patient Health Questionnaire-2. Patients endorsing either one or both items were then given the Patient Health Questionnaire-9, a nine-item depression assessment tool. Patients with mild or worse depression were offered a referral to a mental health care provider. RESULTS: Eighteen of 64 patients (28 %) endorsed one or both items on the PHQ-2. Thirteen of 18 patients with a positive PHQ-2 screen completed the PHQ-9, with mean score of 10.2 (SD 3.91), suggesting moderate depression. PHQ-9 item 4, evaluating fatigue, was positive in 12 patients, and PHQ-9 item 9, evaluating suicidal ideation, was never reported. Only 1 of 18 patients with a positive PHQ-2 screen was being followed by a psychiatrist, and no patient accepted a new referral to a mental health provider. CONCLUSIONS: The PHQ-2 and PHQ-9 modules are an effective means of depression screening in a busy, outpatient clinic. A high prevalence of depression was reported; yet, suicidal ideation was not reported. Depression severity ranged from mild to severe. The most endorsed PHQ-9 item was fatigue, although it is uncertain if this reflects a symptom of depression, a sequela of lung cancer itself, or both. The lung cancer patients in this sample who reported depression were unlikely to receive mental health services.

Validation of a needs-based biopsychosocial distress instrument for cancer patients.

OBJECTIVE: People with cancer may experience distress related to diagnoses, disease-related symptoms, and treatment side effects. Assessment of cancer-related needs can facilitate timely triage and intervention and contribute to individualized comprehensive cancer care. This study assessed the internal consistency, test-retest reliability and construct validity of the Cancer Needs Distress Inventory (CaNDI), a self-report, needs-based measure of cancer-related distress. METHODS: A sample of 100 patients (27% male) with various cancer diagnoses completed the CaNDI, Hospital Anxiety and Depression Scale, Brief Symptom Inventory, Functional Assessment of Cancer Therapy-General, and the Paulhus Deception Scales. RESULTS: The CaNDI total and depressive and anxiety subscale scores all demonstrated excellent test-retest reliability and moderate to high correlations with other measures of these constructs. The instrument was minimally confounded by social desirability and provided high sensitivity and specificity in detecting depression and anxiety. CONCLUSIONS: Initial results suggest that the CaNDI has strong psychometric properties and may be a useful addition to cancer patient needs assessment, research and care.

Long-term course of pain in breast cancer survivors: a 4-year longitudinal study.

After successful treatment of early breast cancer, many women still report pain symptoms, and attribute them to the previous illness or its treatment. However, knowledge about the long-term course of pain in breast cancer is limited. Baseline assessment included 3,088 women who received a breast cancer diagnosis on average 2 years prior to enrollment, and who completed typical medical treatments. After 4 years, a subsample of 2,160 recurrence-free women (70%) was re-assessed. The major outcome variable was the composite index for general pain symptoms. Over the 4-year course, a slight but significant increase in pain was reported. If only medical variables were examined, a triple interaction between surgery type, breast cancer stage, and time indicated that pain scores increased in most subgroups, while they decreased in stage II women after mastectomy and stage III women after lumpectomy. Using a regression analytical approach, psychological and other variables added significantly to the prediction of pain persistence. Regression analysis revealed that pain symptoms increased in those women taking tamoxifen at baseline, in those reporting depression at baseline or stressful life events during the first 12 months after enrollment. Exercise at baseline had a beneficial effect on pain recovery. The persistence or increase of pain symptoms in women surviving breast cancer is associated with some medical factors (surgery type, tamoxifen use), but also with psychological factors. Pain should be a standard outcome variable in the evaluation of cancer treatment programs.

Physical activity, additional breast cancer events, and mortality among early-stage breast cancer survivors: findings from the WHEL Study.

OBJECTIVE: Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality. METHODS: A total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality. RESULTS: Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events. CONCLUSIONS: Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.

Depressed mood and flow-mediated dilation: a systematic review and meta-analysis.

OBJECTIVE: This systematic and quantitative review evaluates the literature on associations between depressed mood and flow-mediated dilation (FMD), a measure of endothelial function, in adults. METHODS: Published English-language articles (through December 2010) were identified from literature searches, assessed for data extraction, and evaluated for quality. RESULTS: The literature includes cross-sectional (n = 9) and retrospective examinations (n = 3) of how FMD correlates with clinical or subclinical depression in healthy adults and cardiovascular patients (total N across 12 studies = 1491). FMD was assessed using a variety of methodologies. Samples were predominately older white and Asian subjects with higher socioeconomic status. In eight of the 12 articles selected for this review, at least one significant inverse association was noted between depressed mood and FMD, with primarily moderate effect sizes. The overall meta-analysis (random-effects model) revealed a combined effect size of correlation coefficient r = 0.19 (95% confidence interval = 0.08-0.29, p = .001). Significant combined effects were found for subgroups of studies that a) received better quality ratings (r = 0.29), b) examined patients with cardiovascular disease or with cardiovascular disease risk factors/comorbidity (r = 0.29), c) used maximum vasodilation to quantify FMD (r = 0.27), and d) assessed samples that had a mean age of 55 years and older (r = 0.15). CONCLUSIONS: Diverse studies support the inverse correlation between depressed mood and endothelial function, as measured by FMD. This literature would be strengthened by prospective studies, increased methodological consistency in FMD testing, and broader sampling (e.g., African Americans, younger age, lower socioeconomic status).

Poor physical health predicts time to additional breast cancer events and mortality in breast cancer survivors.

BACKGROUND: Health-related quality of life has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors. METHODS: Women with early-stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association. RESULTS: There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01-10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psychosocial variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher body mass index, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all). CONCLUSION: Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.

Effects of a weight loss intervention on body mass, fitness, and inflammatory biomarkers in overweight or obese breast cancer survivors.

BACKGROUND: Obesity is characterized by chronic mild inflammation and may influence the risk and progression of cancer. PURPOSE: The current study is an exploratory analysis of the effect of a weight loss intervention that emphasized increased physical activity on inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) at the end of the 16-week intervention period in overweight breast cancer survivors. METHODS: Study participants averaged 56 years of age (N=68). Intervention participants (n=44 vs. 24 controls) participated in a cognitive behavioral therapy-based weight management program as part of an exploratory randomized trial. The intervention incorporated strategies to promote increased physical activity and diet modification. Baseline and 16-week data included height, weight, body composition, physical activity level, and biomarkers IL-6, IL-8, TNF-α, and VEGF. RESULTS: Weight loss was significantly greater in the intervention group than controls (-5.7 [3.5] vs. 0.2 [4.1] kg, P<0.001). Paired t tests noted favorable changes in physical activity level (P<0.001 intervention, P=0.70 control), marginally lower IL-6 levels (P=0.06 intervention, P=0.25 control) at 16 weeks for participants in the intervention group, and lower TNF-α levels for participants in the intervention (P<0.05) and control groups (P<0.001). Increased physical activity was associated with favorable changes in IL-6 for participants in the intervention group (R(2) =0.18; P<0.03). CONCLUSION: Favorable changes in cytokine levels were observed in association with weight loss in this exploratory study with overweight breast cancer survivors.

A Model for Studying Neuropsychological Effects of Sleep Intervention: The Effect of 3-week Continuous Positive Airway Pressure Treatment.

PURPOSE: Patients with obstructive sleep apnea (OSA) commonly have cognitive complaints. There are few randomized studies that have examined neuropsychological effects of continuous positive airway pressure (CPAP) treatment in patients with OSA. In this double-blind trial, we examined if a 3-week CPAP treatment compared with placebo CPAP treatment has specific therapeutic effects on cognitive impairments in patients with OSA and if there are specific domains of cognitive impairments sensitive to 3-week CPAP treatment. SUBJECTS AND METHODS: Thirty-eight newly diagnosed patients with untreated OSA underwent neuropsychological testing before and after 3-weeks CPAP or Placebo CPAP treatment. The two treatment groups (therapeutic CPAP, and placebo-CPAP) were compared using repeated measures analysis of variance (ANOVA). RESULTS AND CONCLUSION: Impairments in neuropsychological functioning ranged from 2.6% to 47.1% before treatment. In response to 3 weeks of treatment, there was no significant time by treatment interaction for a global deficit score of neuropsychological functioning. Only the Stroop Color (number correct) test showed significant improvement specific to CPAP treatment. The study demonstrates the importance of further randomized placebo controlled studies in this area.

Medical comorbidities predict mortality in women with a history of early stage breast cancer.

This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer. Women (n = 2,542) participating in a randomized diet trial completed a self-administered questionnaire regarding whether they were currently being treated for a wide variety of diseases (cardiovascular, diabetes, gallbladder, gastrointestinal, arthritis, and osteoporosis) and conditions (high blood pressure, elevated cholesterol level). Height and weight were measured at baseline. Participants were followed for a median of 7.3 years (range 0.8-15.0). Cox regression analysis was performed to assess whether comorbidities predicted disease-free and overall survival; hazard ratio (HR) was the measure of association. Overall, there were 406 additional breast cancer events and 242 deaths. Participants with diabetes had over twofold the risk of additional breast cancer events (HR 2.1, 95% CI: 1.3, 3.4) and mortality (HR 2.5, 95% CI: 1.4, 4.4). The presence of multiple comorbidities did not statistically significantly predict additional breast cancer events. However, compared to no comorbidities, participants with 3 or more comorbidities had a HR of 2.1, 95% CI: 1.3, 3.3 for mortality. In conclusion, type 2 diabetes is associated with poor breast cancer prognosis. Given that 85% of deaths were caused by breast cancer, these findings suggest that multiple comorbidities may reduce the likelihood of surviving additional breast cancer events.

Sleep health in U.S. Hispanic population.

The importance of sleep on health has only been recently recognized, and the general public and the medical community are not yet fully knowledgeable about this issue. The great majority of sleep research has been performed in whites of European descent and to a lesser extent in African Americans, making generalization of the findings to other ethnic and racial groups difficult. Very little sleep research has been done in U.S. Hispanics. However, based on the available literature and the high prevalence of risk factors in Hispanics, such as obesity, diabetes, living in the inner city, and use of alcohol, the prevalence of such important sleep disorders such as obstructive sleep apnea and sleep habits such as poor sleep hygiene are suspected to be high. There is also some evidence that acculturation to the U.S. life style may lead to worse sleep habits in Hispanics, including fewer hours of sleep. Two current large NIH sponsored studies of sleep in U.S. Hispanics promise to significantly add to the literature on various sleep disorders such as sleep disordered breathing, insomnia, restless legs syndrome, periodic limb movement disorder, and sleep habits such as short sleep duration and sleep hygiene.

Adverse impact of mood on flow-mediated dilation.

OBJECTIVE: To examine the impact of mood states on endothelial function, as measured noninvasively by brachial artery flow-mediated dilation (FMD). Substantial literature indicates that negative mood is linked to cardiovascular disease (CVD). However, the mechanisms underlying this relationship are not well defined. CVD is often preceded by dysfunction of the endothelium. METHODS: Healthy adults (n = 70; mean age, 36 years) completed the Profile of Mood States (POMS), which contains six subscales (depression/dejection; tension/anxiety; anger/hostility; confusion/bewilderment; fatigue/inertia; vigor/activity) that are used to compute a total mood disturbance score for overall psychological distress. FMD was calculated (maximum percentage change in brachial artery diameter) from ultrasound assessment of arterial diameter at baseline and for 10 minutes after occlusion. RESULTS: Regressions showed that increases in POMS total mood disturbance scores were associated with decreases in endothelial function. Mood disturbance explained 10% of the variance in FMD (p < .01), after controlling for age, sex, mean arterial pressure, body mass index, and socially desirable response bias. An exploratory set of separate regressions conducted to decompose the link between FMD and total mood disturbance revealed that the following POMS subscales were inversely correlated with FMD: depression/dejection, tension/anxiety, anger/hostility, fatigue/inertia (p's < .05), and confusion/bewilderment (p < .01). CONCLUSIONS: Mood disturbance could contribute to CVD via impaired vasodilation. These preliminary results show that even mild levels of adverse psychological states, particularly depressed, anxious, angry, confused, and fatigued states, might be linked to increased cardiovascular risk.

Endothelial function: the impact of objective and subjective socioeconomic status on flow-mediated dilation.

BACKGROUND: Although objective and subjective indicators of socioeconomic status (SES) are linked to cardiovascular disease (CVD), little is known about their relationship to endothelial dysfunction, which often precedes CVD. PURPOSE: This study examined how objective and subjective SES relate to brachial artery flow-mediated dilation (FMD). METHODS: FMD was assessed in 72 healthy adults (mean age 36 years). The MacArthur Scale of Subjective Social Status assessed perceived social standing in the USA (SSS-USA) and local community (SSS-Community). Objective SES measures included income and the Hollingshead Two-Factor Index of Social Position (education, occupation). RESULTS: Adjusted regressions revealed that SSS-Community positively correlated with FMD (p < 0.05) and explained 8% of the variance. No other SES measures were significant for FMD. The association between FMD and SSS-Community remained significant (p < 0.01) after adjustment for objective SES and other covariates. CONCLUSIONS: Lower subjective social status in one's community may be linked to CVD via impaired vasodilation.

Symptom control in stem cell transplantation: a multidisciplinary palliative care team approach. Part 2: psychosocial concerns.

Stem cell transplantation (SCT) offers a potential cure for patients with otherwise incurable benign and malignant disorders. However, the treatment will cause considerable physical, social, psychological, and spiritual suffering. In part 1 of this review, the management of the physical symptoms was reviewed. In part 2, we discuss the approaches to managing the other aspects of distress that are primarily psychological, social, and spiritual in nature. In practice, these dimensions are not so easily distinguished; the division between physical and psychological symptoms is blurred, and physical symptoms are often interrelated with the patient's emotional status and social support.

Symptom control in stem cell transplantation: a multidisciplinary palliative care team approach. Part 1: Physical symptoms.

Stem cell transplantation (SCT) offers a potential cure for patients with otherwise incurable benign and malignant disorders, but the arduous SCT process may cause considerable physical, social, psychological, and spiritual suffering. Relief of suffering associated with SCT begins by understanding the patient experience and the SCT culture. Symptom burden is the combined impact of all disease- or therapy-related symptoms on the patient's ability to function. In approaching symptom management, the division between physical and psychological symptoms is blurred; physical symptoms are often interrelated with the patient's emotional status and social support. Physical symptoms that frequently occur in SCT include pain, nausea, mucositis, diarrhea, and delirium. At the same time, SCT is recognized as one of the most stressful treatments in modern cancer care, resulting in psychological distress, social isolation, and role changes. Psychological symptoms include depression/ anxiety, grief/loss, demoralization, and anger. Based on our experience on an academic SCT ward for adults, we review physical, psychological, social, and spiritual symptoms during the course of SCT in a two-part series and offer an approach to their management. This month, in part I, we focus on physical symptoms linked to SCT. In a future issue, part II will highlight psychosocial concerns in SCT.

Relationships between cardiorespiratory fitness, physical activity, and psychosocial variables in overweight and obese breast cancer survivors.

BACKGROUND: Breast cancer survivors not only experience distressing physical symptoms associated with treatments, but also are faced with psychosocial challenges. Despite growing scientific evidence that physical activity (PA) may mitigate psychosocial distress experienced by women treated for breast cancer, the literature is equivocal. PURPOSE: This study investigated the relationships between cardiorespiratory fitness (CRF), PA, and psychosocial factors in breast cancer survivors. METHOD: Data involving overweight or obese breast cancer survivors (N = 260) were examined. CRF was determined by a submaximal graded exercise test. PA, depressive symptoms, total fatigue, and global self-esteem were assessed with self-report measures. Pearson's correlations were conducted to determine associations among CRF, PA, depressive symptoms, total fatigue, and global self-esteem. Multiple regression models, with age and body mass index as covariates, were performed using continuous levels for CRF and PA. RESULTS: Bivariate correlations suggested that CRF and PA were unrelated to the psychosocial variables. One of the regression models identified a marginally significant (P = 0.06) inverse association between depressive symptoms and PA. CONCLUSION: CRF and PA were not associated with psychosocial factors in this sample of breast cancer survivors. However, minimal PA was reported by the majority of participants, so low PA variability likely influenced these findings.

Arousal frequency is associated with increased fatigue in obstructive sleep apnea.

OBJECTIVE: Fatigue is an important and often underemphasized symptom in patients with obstructive sleep apnea (OSA). Sleep fragmentation, i.e., arousals and disruptions in sleep architecture, is common in patients with OSA and may potentially contribute to their fatigue. We hypothesized that arousal frequency and changes in sleep architecture contribute to the fatigue experienced by patients with OSA. DESIGN: Seventy-three patients with diagnosed but untreated OSA (AHI > or = 15) were enrolled in this study. A baseline polysomnogram was obtained, and fatigue was measured with the Multidimensional Fatigue Symptom Inventory-short form (MFSI-sf). We evaluated the association between fatigue and arousals and various polysomongraphic variables, including sleep stages and sleep efficiency. RESULTS: Significant correlations between MFSI-sf subscale scores and various arousal indices were noted. Emotional fatigue scores were associated with total arousal index (r = 0.416, p = .021), respiratory movement arousal index (r = 0.346, p = .025), and spontaneous movement arousal index (r = 0.378, p = .025). Physical fatigue scores were associated with total arousal index (r = 0.360, p = .033) and respiratory movement arousal index (r = 0.304, p = .040). Percent of stage 1 sleep and REM sleep were also associated with physical and emotional fatigue scores. Hierarchal linear regression analysis demonstrated that emotional fatigue scores were independently associated with spontaneous movement arousals after controlling for age, body mass index, depression, and sleep apnea severity. CONCLUSIONS: These findings suggest that arousals may contribute to the fatigue seen in patients with OSA.

Relationship between inflammation and cognitive function in obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.