Don't hold PAT: watch for and correct oximetry artifact.

This study evaluated the accuracy of the algorithmic oxygen saturation (SpO2) nadir detection of WatchPAT (Zoll/Itamar, Caesarea, Israel) compared with visual inspection in a real-world setting. SpO2 tracings for 209 consecutive adult WatchPAT recordings were reviewed for SpO2 artifact, with erroneous SpO2 data removed manually. Error rates for SpO2 minima were determined across all studies, and relationships between correct and erroneous studies examined. The overall error rate for SpO2 nadir was 22.5%. Erroneous studies had overall less time spent at SpO2 ≤ 88%, higher true SpO2 nadir, lower mean body mass index, and greater artifact time; however, these variables were not associated with the magnitude of discrepancy between manual and algorithmically derived SpO2 minima. These data demonstrate that SpO2 nadir determined by WatchPAT algorithms should not be considered universally accurate. Like other home sleep apnea tests, visual inspection and manual correction of the study data are often required to derive accurate clinical results. CITATION: Plante DT, Rumble ME. Don't hold PAT: watch for and correct oximetry artifact. J Clin Sleep Med. 2023;19(12):2113-2116.

Sleep and Women's Mental Health.

Women have increased risks for both sleep disturbances and disorders and for mental health issues throughout their lives, starting in adolescence. Women have a higher prevalence of insomnia disorder and restless legs syndrome (RLS) versus men, and obstructive sleep apnea (OSA) is more likely as women age. Hormonal transitions are important to consider in women's sleep. For women, insomnia, OSA, and RLS are predictive of depression, and insomnia and sleep-disordered breathing are predictive of Alzheimer disease. These findings underscore the importance of assessment, treatment, and future research examining sleep and mental health in women, given their unique and increased vulnerability.

Psychological and physical function in allogeneic hematopoietic cell transplant survivors with chronic graft-versus-host disease.

PURPOSE: Chronic graft-versus-host disease (cGVHD) is a common late complication of allogeneic hematopoietic cell transplantation (HCT). This study comprehensively evaluated physical and psychological function among individuals with cGVHD. Additional aims were to investigate relationships between disease severity and psychological and physical function, and to investigate patterns of psychological and physical function by disease site. METHOD: Adults at least 6 months post allogeneic HCT were enrolled and either had cGVHD (n =59) or served as a reference sample of HCT survivors with no cGVHD history (n = 19). Participants completed self-report measures of depression, anxiety, fatigue, insomnia, pain, cognition, and sexual function and had a comprehensive clinical evaluation of cGVHD using NIH consensus scoring criteria. Participants with cGVHD were stratified by disease severity and site and compared to the reference group with no cGVHD. RESULTS: Participants with mild cGVHD had comparable psychological and physical symptoms to the reference sample, while participants with moderate cGVHD experienced more severe anxiety and problems with sexual function, and participants with severe cGVHD experienced more severe depressive symptoms and pain compared to the reference sample. Participants with cGVHD manifesting in the skin and GI tract had the most severe symptoms, including mood disturbance, fatigue, and pain. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Results suggest that patients with more severe cGVHD and those with cGVHD manifesting in the skin, GI tract, and lungs are at risk for poorer psychological and physical outcomes and may benefit from proactive interventions to optimize function.

A biobehavioral intervention to enhance recovery following hematopoietic cell transplantation: Protocol for a feasibility and acceptability randomized control trial.

Background: Insomnia, fatigue, and depression are among the most persistent and distressing concerns for hematologic cancer patients recovering from hematopoietic cell transplantation (HCT). This study will evaluate a novel behavioral intervention, Restoring Sleep and Energy after Transplant (ReSET), designed to alleviate insomnia, fatigue, and depression by improving rest-activity patterns. Evidence-based behavioral strategies to improve nighttime sleep and increase non-sedentary daytime activity will be combined to optimize 24-h rest-activity patterns. Methods: The protocol herein evaluates the feasibility and acceptability of ReSET by conducting a pilot randomized controlled trial to compare the intervention with usual care. Adults undergoing HCT will be randomly assigned to ReSET or usual care. The ReSET arm will receive 3 face-to-face sessions and telephone coaching delivered in an individual format tailored to each patient. Patient-reported insomnia, fatigue, and depression will be the primary outcome measures. Actigraphy will be used to objectively quantify rest-activity patterns. Semi-structured interviews will evaluate participant satisfaction with ReSET. The goals are to determine: (1) participant satisfaction with and acceptability of the behavioral techniques; (2) facilitator fidelity and participant uptake of key intervention components; (3) ability to recruit, retain, and collect complete data from participants; (4) participant willingness to be randomized and acceptability of the control condition; and (5) validity and acceptability of the assessment strategy. Conclusion: The overarching goal is to optimize recovery following HCT with a brief, non-invasive intervention that can be implemented as a part of routine clinical care.

Examining suicide assessment measures for research use: Using item response theory to optimize psychometric assessment for research on suicidal ideation in major depressive disorder.

INTRODUCTION: Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need. METHODS: We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome. RESULTS: All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation. CONCLUSIONS: The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores.

Blinding and bias in a hypnotic clinical trial.

OBJECTIVES: Information is lacking regarding how commonly unblinding of treatment assignment occurs in hypnotic randomized clinic trials (RCTs). We now report the "best guesses" of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). METHODS: REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors. At the conclusion of study participation, 89 of the participants in this study, the study coordinators, and the study physicians each independently recorded their "best guess" of the treatment assigned. RESULTS: Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time, and none were different from chance alone. Agreement between patient/coordinator, patient/doctor, and coordinator/doctor dyads were 75%-78% with no significant differences in agreement between the dyads. CONCLUSIONS: "Best guesses" of all parties were not different from chance, suggesting that the blind was maintained and that assessment bias was minimized in this RCT of zolpidem ER versus placebo. Our results may not apply to other hypnotics or other RCT designs.

An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation.

STUDY OBJECTIVES: Sleep disturbance is significantly associated with suicidal ideation. However, the majority of past research has examined the relationship between insomnia and suicidality. The current exploratory study examined the relationship of circadian rhythm dysregulation (eveningness, seasonality, and rhythmicity) with suicidality. METHODS: We examined the association of insomnia, eveningness, seasonality, and rhythmicity with suicidal ideation in 103 participants with depression, insomnia, and suicidality within a larger 8-week double-blinded randomized control trial primarily examining whether cautious use of zolpidem extended-release or placebo reduced suicidal ideation. All participants additionally received an open-label selective serotonin reuptake inhibitor. Methodological strengths of the current analyses included consideration of multiple sleep-wake constructs, adjustment for relevant covariates, investigation of relationships over the course of treatment, and use of both self-report measures and objective measurement with actigraphy. RESULTS: Over the course of treatment, self-reported eveningness and greater insomnia severity were independently correlated with greater suicidal ideation, whereas actigraphic delayed sleep timing was related to suicidal ideation at a trend level. At the end of treatment, those with greater suicidal ideation demonstrated lower actigraphic activity levels. There were no significant relationships between self-reported seasonality and actigraphic measures of sleep disturbance and suicidality. CONCLUSIONS: Self-reported delays in sleep timing, objectively lower activity levels, and self-reported insomnia severity correlated independently with greater suicidal ideation in those with depression, insomnia, and suicidality. These exploratory findings highlight the need to consider sleep-wake constructs more broadly in those with suicidality in future research studies in order to improve more definitively both assessment and intervention efforts. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Reducing Suicidal Ideation through Insomnia Treatment; URL: https://clinicaltrials.gov/ct2/show/NCT01689909; Identifier: NCT01689909 Rumble ME, McCall MV, Dickson DA, Krystal AD, Rosenquist PB, Benca RM. An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation. J Clin Sleep Med. 2020;16(8):XXX-XXX.

Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial.

OBJECTIVE: The authors sought to determine whether targeted treatment of insomnia with controlled-release zolpidem (zolpidem-CR) in suicidal adults with insomnia would provide a reduction in suicidal ideation superior to placebo. METHODS: Reducing Suicidal Ideation Through Insomnia Treatment was an 8-week three-site double-blind placebo-controlled parallel-group randomized controlled trial of zolpidem-CR hypnotic therapy compared with placebo, in conjunction with an open-label selective serotonin reuptake inhibitor. Participants were medication-free 18- to 65-year-olds with major depressive disorder, insomnia, and suicidal ideation. Suicidal ideation was the main outcome, measured first by the Scale for Suicide Ideation and second by the Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: A total of 103 participants were randomly assigned to receive zolpidem-CR (N=51) or placebo (N=52) (64 women and 39 men; mean age=40.5 years). Zolpidem-CR had a robust anti-insomnia effect, especially in patients with the most severe insomnia symptoms. No significant treatment effect was observed on the Scale for Suicide Ideation (least squares mean estimate=-0.56, SE=0.83, 95% CI=-2.19, 1.08), but the reduction in scores was significantly positively related to improvement in insomnia after accounting for the effect of other depression symptoms. The C-SSRS indicated that zolpidem-CR had a significant treatment effect (least squares mean estimate=-0.26, SE=0.12, 95% CI=-0.50, -0.02). The advantage for zolpidem-CR in reducing suicidal ideation on the C-SSRS was greater in patients with more severe insomnia. No deaths or suicide attempts occurred. CONCLUSIONS: Although the results do not support the routine prescription of hypnotic medication for mitigating suicidal ideation in all depressed outpatients with insomnia, they suggest that coprescription of a hypnotic during initiation of an antidepressant may be beneficial in suicidal outpatients, especially in patients with severe insomnia.

Prevalence of obstructive sleep apnea in suicidal patients with major depressive disorder.

In this paper, we report the rate of previously undiagnosed obstructive sleep apnea (OSA) in a randomized clinical trial (RCT) of suicidal patients with major depressive disorder (MDD). One hundred and twenty-five suicidal adults with MDD were recruited into a RCT. None were suspected to have OSA. Fourteen percent met diagnostic criteria for OSA. The Apnea Hypopnea Index (AHI) was predicted by increasing age, male sex, and higher Body Mass Index. However, neither the degree of daytime sleepiness nor the degree of insomnia predicted AHI severity. A high degree of suspicion is warranted for OSA in suicidal patients with MDD, and for patients with treatment-resistant depression. ClinicalTrials.gov identifier: NCT01689909.

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

The relationship of person-specific eveningness chronotype, greater seasonality, and less rhythmicity to suicidal behavior: A literature review.

BACKGROUND: Epidemiological data have demonstrated seasonal and circadian patterns of suicidal deaths. Several reviews and meta-analyses have confirmed the relationship between sleep disturbance and suicidality. However, these reviews/meta-analyses have not focused on seasonal and circadian dysfunction in relation to suicidality, despite the common presence of this dysfunction in patients with mood disorders. Thus, the current literature review analyzed studies investigating person-specific chronotype, seasonality, and rhythmicity in relation to suicidal thoughts and behaviors. METHODS: Study authors reviewed articles related to individual-level chronotype, seasonality, and rhythmicity and suicidality that were written in English and not case reports or reviews. RESULTS: This review supports a relationship between an eveningness chronotype, greater seasonality, and decreased rhythmicity with suicidal thoughts and behaviors in those with unipolar depression, as well as in other psychiatric disorders and in children/adolescents. LIMITATIONS: These findings need to be explored more fully in mood disordered populations and other psychiatric populations, in both adults and children, with objective measurement such as actigraphy, and with chronotype, seasonality, and rhythmicity as well as broader sleep disturbance measurement all included so the construct(s) most strongly linked to suicidality can be best identified. CONCLUSIONS: Eveningness, greater seasonality, and less rhythmicity should be considered in individuals who may be at risk for suicidal thoughts and behaviors and may be helpful in further tailoring assessment and treatment to improve patient outcome.

Sex Differences in the Relationship Between Depressive Symptoms and Actigraphic Assessments of Sleep and Rest-Activity Rhythms in a Population-Based Sample.

OBJECTIVE: Depression is often associated with disruptions in sleep and circadian rhythms. We aimed to confirm these relationships via actigraphic assessment in a large, population-based sample and test whether sex moderates these relationships. METHODS: A total of 418 participants (age = 35-85 years, mean [standard deviation] = 57.04 [11.47]) completed questionnaires and 1 week of actigraphy, used to calculate sleep and rest-activity statistics including mesor (mean activity level), amplitude (height of rhythm), and acrophase (time of day that rhythm peaks). RESULTS: Depressive symptoms, assessed via Center for Epidemiologic Studies Depression Scale, were associated with disrupted sleep and rest-activity rhythms. Furthermore, men demonstrated longer sleep onset latency (SOL, B = -13.28, p < .001), longer wake time after sleep onset (B = -6.26, p < .01), lower sleep efficiency (B = 5.91, p < .001), and lower total sleep time (TST, B = 33.16, p < .001) than women. Sex moderated the relationship between depression and SOL, TST, mesor, and amplitude; sex-stratified models revealed that higher depression scores were associated with greater SOL (B = 1.05, p < .001) and less TST (B = -0.87, p < .10) for women with higher depressive symptoms, but lower mesor (B = -1.75, p < .01) and amplitude (B = -1.94, p < .01) for men with higher depressive symptoms. CONCLUSIONS: Depressive symptoms were related to disrupted sleep continuity and rest-activity rhythms in this population-based sample; however, these relationships differed by sex. Women with greater depressive symptoms exhibited difficulty with sleep continuity, whereas men with greater depressive symptoms demonstrated disruption throughout the 24-hour rhythm.

Regional Patterns of Elevated Alpha and High-Frequency Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic Insomnia: A Pilot Study.

STUDY OBJECTIVES: To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG). METHODS: All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging. RESULTS: The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4-8 Hz) and alpha (8-12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls. CONCLUSIONS: These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain.

Effects of partial sleep deprivation on slow waves during non-rapid eye movement sleep: A high density EEG investigation.

OBJECTIVE: Changes in slow waves during non-rapid eye movement (NREM) sleep in response to acute total sleep deprivation are well-established measures of sleep homeostasis. This investigation utilized high-density electroencephalography (hdEEG) to examine topographic changes in slow waves during repeated partial sleep deprivation. METHODS: Twenty-four participants underwent a 6-day sleep restriction protocol. Spectral and period-amplitude analyses of sleep hdEEG data were used to examine changes in slow wave energy, count, amplitude, and slope relative to baseline. RESULTS: Changes in slow wave energy were dependent on the quantity of NREM sleep utilized for analysis, with widespread increases during sleep restriction and recovery when comparing data from the first portion of the sleep period, but restricted to recovery sleep if the entire sleep episode was considered. Period-amplitude analysis was less dependent on the quantity of NREM sleep utilized, and demonstrated topographic changes in the count, amplitude, and distribution of slow waves, with frontal increases in slow wave amplitude, numbers of high-amplitude waves, and amplitude/slopes of low amplitude waves resulting from partial sleep deprivation. CONCLUSIONS: Topographic changes in slow waves occur across the course of partial sleep restriction and recovery. SIGNIFICANCE: These results demonstrate a homeostatic response to partial sleep loss in humans.

Biopsychosocial predictors of pain among women recovering from surgery for endometrial cancer.

OBJECTIVE: This study investigated post-surgical changes in pain among endometrial cancer patients, as well as the extent to which emotional distress and inflammatory and regulatory cytokine levels were associated with pain. METHODS: Women (N=71) who underwent surgery for endometrial cancer completed questionnaires assessing pain intensity and interference, depression, and anxiety at 1week, 4weeks, and 16weeks post-surgery. Participants also provided a blood sample for the analysis of a panel of 7 cytokines at the same time points. RESULTS: Participants showed significant declines in pain intensity and pain interference from 1week to 4weeks post-surgery, after which pain remained stable. After adjusting for time since surgery, surgery type, adjuvant therapy, disease stage, age, and BMI, mixed-effects linear regression models indicated that greater depression and anxiety were associated with both greater pain intensity and interference. Higher levels of circulating IL-6 were also correlated with greater pain intensity, but not interference. Fixed-effects linear regression models indicated that temporal variation in depression, anxiety, and IL-6 within individual patients was associated with corresponding changes in pain. Pain symptoms were maximal when anxiety, depression, and IL-6 were highest. No other cytokines were associated with changes in pain. CONCLUSION: These findings indicate that depression, anxiety, and IL-6 may exacerbate pain during the recovery period following surgery for a gynecologic malignancy. Targeting these psychological processes and the proinflammatory cytokine IL-6 in women with more severe and persistent pain may help to reduce suffering and improve post-surgical recovery.

Sleep Disturbances in Mood Disorders.

The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed.

Circadian actigraphic rest-activity rhythms following surgery for endometrial cancer: A prospective, longitudinal study.

OBJECTIVE: To investigate (1) circadian rest-activity rhythm disturbances among endometrial cancer patients as they recover from surgery in comparison to a historical reference group of women with no cancer history and (2) health- and treatment-related predictors of dysregulated rest-activity rhythms in endometrial cancer patients. METHODS: 60 endometrial cancer patients participated in a prospective, longitudinal study with actigraphic assessment at 1week, 1month, and 4months post-surgery. 60 women without cancer from an epidemiological sample completed one actigraphic assessment, acting as a reference group. RESULTS: On average, results revealed initial significant rest-activity dysregulation at 1week and 1month post-surgery for the endometrial cancer group and then significant recovery in rest-activity patterns at 4months post-surgery. Similarly, the cancer group had significantly more impaired rhythms than the reference group at 1week post-surgery, but demonstrated comparable rhythms by 4months post-surgery. Among the health- and treatment-related variables examined, obesity and receipt of more invasive surgery were found to predict more impaired rhythms at all time points. CONCLUSION(S): The current study highlights significant disturbances in rest-activity patterns for endometrial cancer patients initially during surgical recovery followed by improvement in these patterns by 4months post-surgery; however, obese patients and those having more invasive surgery demonstrated more impaired rest-activity patterns throughout the 4-month recovery period. Further research is warranted to understand how more impaired rest-activity patterns relate to health and quality of life outcomes.

Sleep Related Cognitions in Individuals with Symptoms of Insomnia and Depression.

STUDY OBJECTIVES: Depression has been identified as the most common condition comorbid to insomnia, with findings pointing to the possibility that these disorders may be causally related to each other or may share common mechanisms. Some have suggested that comorbid insomnia and depression may have a different clinical course than either condition alone, and may thus require specific treatment procedures. In this report we examined the clinical characteristics of individuals referred to an academic sleep center who report comorbid symptoms of insomnia and depression and those with symptoms of insomnia outside the context of meaningful depression, and we identified differences between these groups with regard to several cognitive-related variables. METHODS: Logistic regression analyses examined whether past week worry, dysfunctional beliefs about sleep, and insomnia symptom-focused rumination predicted group membership. RESULTS: Individuals with comorbid symptoms of insomnia and depression reported more past-week worry, dysfunctional beliefs about sleep, and insomnia symptom-focused rumination, than those with symptoms of insomnia without significant depression symptoms. When including all three cognitive-related variables in our model, those with comorbid symptoms reported more severe insomnia symptom-focused rumination, even when controlling for insomnia and mental health severity, among other relevant covariates. CONCLUSION: The findings contribute to our understanding of the complex nature of comorbid symptoms of insomnia and depression and the specific symptom burden experienced by those with significant depression symptoms in the presence of insomnia. The findings also highlight the need for increased clinical attention to the sleep-focused rumination reported by these patients.