Investigating brain dynamics and their association with cognitive control in opioid use disorder using naturalistic and drug cue paradigms.

Objectives: Opioid use disorder (OUD) impacts millions of people worldwide. The prevalence and debilitating effects of OUD present a pressing need to understand its neural mechanisms to provide more targeted interventions. Prior studies have linked altered functioning in large-scale brain networks with clinical symptoms and outcomes in OUD. However, these investigations often do not consider how brain responses change over time. Time-varying brain network engagement can convey clinically relevant information not captured by static brain measures. Methods: We investigated brain dynamic alterations in individuals with OUD by applying a new multivariate computational framework to movie-watching (i.e., naturalistic; N=76) and task-based (N=70) fMRI. We further probed the associations between cognitive control and brain dynamics during a separate drug cue paradigm in individuals with OUD. Results: Compared to healthy controls (N=97), individuals with OUD showed decreased variability in the engagement of recurring brain states during movie-watching. We also found that worse cognitive control was linked to decreased variability during the rest period when no opioid-related stimuli were present. Conclusions: These findings suggest that individuals with OUD may experience greater difficulty in effectively engaging brain networks in response to evolving internal or external demands. Such inflexibility may contribute to aberrant response inhibition and biased attention toward opioid-related stimuli, two hallmark characteristics of OUD. By incorporating temporal information, the current study introduces novel information about how brain dynamics are altered in individuals with OUD and their behavioral implications.

"What if that's your last sleep?" A qualitative exploration of the trauma of incarceration and sleep.

Study Background/Objectives: Sleep is an underexplored factor in the health of people involved in the criminal legal system. This study addresses the paucity of research on how individual, social, and physical environmental factors impact sleep health during and after incarceration by highlighting the voices of people involved in the criminal legal system through a community-engaged qualitative research approach. Methods: We conducted 20 semi-structured interviews with men recently released from prison for a study on trauma and healthcare during incarceration and after release. Interviews were coded and analyzed using reflexive thematic analysis and a critical realist framework. Our research team included people with a history of incarceration who performed central roles in the research process. Results: Three themes emerged from participants' descriptions of sleep during and after incarceration: (1) concerns about health contributing to sleep problems, (2) lack of access to treatment for sleep disorders leading to ongoing sleep problems, and (3) issues of safety contributing to sleep problems during incarceration and after release. Conclusions: This study identifies factors and domains influencing sleep during and after incarceration. By identifying which interpersonal, environmental, and structural factors impact sleep quality, medical and carceral staff are better equipped to ameliorate sleep health disparities within populations with a history of incarceration and those actively bound by the criminal legal system. Future research should examine other factors impacting sleep in incarcerated and recently released populations and develop multi-level interventions to improve sleep health. This paper is part of the Sleep and Circadian Health in the Justice System Collection.

Association of Periodic Limb Movements and Obstructive Sleep Apnea With Risk of Cardiovascular Disease and Mortality.

BACKGROUND: Obstructive sleep apnea is a well-established risk factor for cardiovascular disease (CVD). Recent studies have also linked periodic limb movements during sleep to CVD. We aimed to determine whether periodic limb movements during sleep and obstructive sleep apnea are independent or synergistic factors for CVD events or death. METHODS AND RESULTS: We examined data from 1049 US veterans with an apnea-hypopnea index (AHI) <30 events/hour. The primary outcome was incident CVD or death. Cox proportional hazards regression assessed the relationships between the AHI, periodic limb movement index (PLMI), and the AHI×PLMI interaction with the primary outcome. We then examined whether AHI and PLMI were associated with primary outcome after adjustment for age, sex, race and ethnicity, obesity, baseline risk of mortality, and Charlson Comorbidity Index. During a median follow-up of 5.1 years, 237 of 1049 participants developed incident CVD or died. Unadjusted analyses showed an increased risk of the primary outcome with every 10-event/hour increase in PLMI (hazard ratio [HR], 1.08 [95% CI, 1.05-1.13]) and AHI (HR, 1.17 [95% CI, 1.01- 1.37]). Assessment associations of AHI and PLMI and their interaction with the primary outcome revealed no significant interaction between PLMI and AHI. In fully adjusted analyses, PLMI, but not AHI, was associated with an increased risk of primary outcome: HR of 1.05 (95% CI, 1.00-1.09) per every 10 events/hour. Results were similar after adjusting with Framingham risk score. CONCLUSIONS: Our study revealed periodic limb movements during sleep as a risk factor for incident CVD or death among those who had AHI <30 events/hour, without synergistic association between periodic limb movements during sleep and obstructive sleep apnea.

Suboptimal Sleep Duration Is Associated With Poorer Neuroimaging Brain Health Profiles in Middle-Aged Individuals Without Stroke or Dementia.

BACKGROUND: The American Heart Association's Life's Simple 7, a public health construct capturing key determinants of cardiovascular health, became the Life's Essential 8 after the addition of sleep duration. The authors tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults. METHODS AND RESULTS: The authors conducted a prospective magnetic resonance neuroimaging study in middle-aged individuals without stroke or dementia enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers included the presence of white matter hyperintensities (WMHs), volume of WMH, and fractional anisotropy, with the latter evaluated as the average of 48 white matter tracts. Multivariable logistic and linear regression models were used to test for an association between sleep duration and these neuroimaging markers. The authors evaluated 39 771 middle-aged individuals. Of these, 28 912 (72.7%) had optimal, 8468 (21.3%) had short, and 2391 (6%) had long sleep duration. Compared with optimal sleep, short sleep was associated with higher risk of WMH presence (odds ratio, 1.11 [95% CI, 1.05-1.18]; P<0.001), larger WMH volume (beta=0.06 [95% CI, 0.04-0.08]; P<0.001), and worse fractional anisotropy profiles (beta=-0.04 [95% CI, -0.06 to -0.02]; P=0.001). Compared with optimal sleep, long sleep duration was associated with larger WMH volume (beta=0.04 [95% CI, 0.01-0.08]; P=0.02) and worse fractional anisotropy profiles (beta=-0.06 [95% CI, -0.1 to -0.02]; P=0.002), but not with WMH presence (P=0.6). CONCLUSIONS: Among middle-aged adults without stroke or dementia, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because these neuroimaging markers precede stroke and dementia by several years, these findings are consistent with other findings evaluating early interventions to improve this modifiable risk factor.

Insomnia and Early Incident Atrial Fibrillation: A 16-Year Cohort Study of Younger Men and Women Veterans.

Background There is growing consideration of sleep disturbances and disorders in early cardiovascular risk, including atrial fibrillation (AF). Obstructive sleep apnea confers risk for AF but is highly comorbid with insomnia, another common sleep disorder. We sought to first determine the association of insomnia and early incident AF risk, and second, to determine if AF onset is earlier among those with insomnia. Methods and Results This retrospective analysis used electronic health records from a cohort study of US veterans who were discharged from military service since October 1, 2001 (ie, post-9/11) and received Veterans Health Administration care, 2001 to 2017. Time-varying, multivariate Cox proportional hazard models were used to examine the independent contribution of insomnia diagnosis to AF incidence while serially adjusting for demographics, lifestyle factors, clinical comorbidities including obstructive sleep apnea and psychiatric disorders, and health care utilization. Overall, 1 063 723 post-9/11 veterans (Mean age=28.2 years, 14% women) were followed for 10 years on average. There were 4168 cases of AF (0.42/1000 person-years). Insomnia was associated with a 32% greater adjusted risk of AF (95% CI, 1.21-1.43), and veterans with insomnia showed AF onset up to 2 years earlier. Insomnia-AF associations were similar after accounting for health care utilization (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.17-1.39]), excluding veterans with obstructive sleep apnea (aHR, 1.38 [95% CI, 1.24-1.53]), and among those with a sleep study (aHR, 1.26 [95% CI, 1.07-1.50]). Conclusions In younger adults, insomnia was independently associated with incident AF. Additional studies should determine if this association differs by sex and if behavioral or pharmacological treatment for insomnia attenuates AF risk.

Sex-Specific Associations of Obstructive Sleep Apnea Risk With Patient Characteristics and Functional Outcomes After Acute Myocardial Infarction: Evidence From the VIRGO Study.

Background Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. Conclusions Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.

Costs and Resource Utilization of People with Stable Heart Failure and Insomnia: Evidence from a Randomized Trial of Cognitive Behavioral Therapy for Insomnia.

OBJECTIVES: Nearly half of patients with chronic heart failure (HF) report insomnia symptoms. The purpose of this study was to examine the impact of CBT-I versus HF self-management on healthcare costs and resource utilization among patients with stable chronic HF who participated in a clinical trial of the effects of CBT-I compared to HF self-management education (attention control) over 1 year. METHODS: We measured resource utilization as self-reported (medical record review) physician office visits, emergency department visits, and inpatient admissions at 3-month intervals for 1 year after enrollment. Costs were estimated by applying price weights to visits and adding self-reported out-of-pocket and indirect costs. Univariate comparisons were made of resource utilization and costs between CBT-I and the HF self-management group. A generalized linear model (GLM) was used to model costs, controlling for covariates. RESULTS: The sample included 150 patients [79 CBT-I; 71 self-management (M age = 62 + 13 years)]. The CBT-I group had 4.2 inpatient hospitalizations vs 4.6 for the self-management group (p = .40). There were 13.1 outpatient visits, in the CBT-I compared with 15.4 outpatient visits (p-value range 0.39-0.81) for the self-management group. Total costs were not significantly different in univariate or ($7,813 CBT-I vs. $7,538 self-management), p = .96) or multivariable analyses. CONCLUSIONS: Among patients with both HF and insomnia, CBT-I and HF self-management were associated with similar resource utilization and total costs. Additional research is needed to estimate the value of CBT-I relative to usual care and other treatments for insomnia in patients with HF.

Suboptimal Sleep Duration is Associated with Poorer Neuroimaging Brain Health Profiles.

Background: Cardiovascular health optimization during middle age benefits brain health. The American Heart Association's Life's Simple 7 recently added sleep duration as a key determinant of cardiovascular health becoming the Life's Essential 8. We tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults. Methods: We conducted a prospective MRI neuroimaging study in middle-aged persons without stroke, dementia, or multiple sclerosis enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers of brain health included white matter hyperintensities (presence and volume) and diffusion tensor imaging metrics (fractional anisotropy and mean diffusivity) evaluated in 48 distinct neuroanatomical regions. We used multivariable logistic and linear regression models, as appropriate, to test for association between sleep duration and neuroimaging markers of brain health. Results: We evaluated 39,502 middle-aged persons (mean age 55, 53% female). Of these, 28,712 (72.7%) had optimal, 8,422 (21.3%) short, and 2,368 (6%) long sleep. Compared to optimal sleep, short sleep was associated with higher risk (OR 1.11; 95% CI 1.05-1.17; P<0.001) and larger volume (beta=0.06, SE=0.01; P<0.001) of white matter hyperintensities, while long sleep was associated with higher volume (beta=0.04, SE=0.02; P=0.01) but not higher risk (P>0.05) of white matter hyperintensities. Short (beta=0.03, SE=0.01; P=0.004) and long sleep (beta=0.07, SE=0.02; P<0.001) were associated with worse fractional anisotropy, while only long sleep associated with worse mean diffusivity (beta=0.05, SE=0.02; P=0.005). Conclusions: Among middle-aged adults without clinically observed neurological disease, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because the evaluated neuroimaging markers precede stroke and dementia by several years, our findings support early interventions aimed at correcting this modifiable risk factor.

Sleep-related predictors of cognition among adults with chronic insomnia and heart failure enrolled in a randomized controlled trial of cognitive behavioral therapy for insomnia.

STUDY OBJECTIVES: Cognitive impairment and insomnia are common in chronic heart failure (HF). We examined the effects of cognitive behavioral therapy for insomnia (CBT-I) and the extent to which demographic, clinical, symptom, and functional characteristics predicted cognition among people with chronic HF and insomnia who participated in a randomized controlled trial of CBT-I. METHODS: Participants with HF were randomized to group-based CBT-I or an attention control (HF self-management education). Outcomes were measured over 1 year. We measured psychomotor vigilance and self-reported cognitive ability (PROMIS Cognitive Abilities Scale), clinical and demographic characteristics, history of sleep apnea, fatigue, pain, insomnia (Insomnia Severity Index), sleepiness (Epworth Sleepiness Scale), Six Minute Walk, EuroQoL Quality of Life, and wrist actigraphy (sleep characteristics and rest-activity rhythms). We used cosinor analysis to compute rest-activity rhythms and general linear models and general estimating equations to test the effects of predictors over 1 year. RESULTS: The sample included 175 participants (mean age = 63 SD = 12.9 Years; 43% women). There was a statistically significant group-time effect on self-reported cognitive function and increases in the proportion of participants, with < 3 psychomotor vigilance lapses in the CBT-I group. Controlling for group-time effects and baseline cognition, decreased sleepiness, improved rest-activity rhythms, and 6-minute walk distance predicted a composite measure of cognition (psychomotor vigilance lapses and self-reported cognition). CONCLUSIONS: CBT-I may improve cognition in adults with chronic HF. A future fully powered randomized controlled trial is needed to confirm the extent to which CBT-I improves multiple dimensions of cognition. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Cognitive Behavioral Therapy for Insomnia: A Self-Management Strategy for Chronic Illness in Heart Failure; URL: https://clinicaltrials.gov/ct2/show/NCT02660385; Identifier: NCT02660385. CITATION: Redeker NS, Conley S, O'Connell M, Geer JH, Yaggi H, Jeon S. Sleep-related predictors of cognition among adults with chronic insomnia and heart failure enrolled in a randomized controlled trial of cognitive behavioral therapy for insomnia. J Clin Sleep Med. 2023;19(6):1073-1081.

Polysomnographic predictors of incident diabetes and pre-diabetes: an analysis of the DREAM study.

STUDY OBJECTIVES: We sought to evaluate sleep measures that better predict incident diabetes and prediabetes in a large cohort of veterans. METHODS: This secondary analysis included 650 patients without baseline diabetes from a multisite observational veterans' cohort. Participants underwent obstructive sleep apnea evaluation via laboratory-based polysomnography between 2000 and 2004 with follow-up through 2012. The primary outcomes were prediabetes and diabetes defined by fasting blood glucose, hemoglobin A1c, or use of glucose-lowering medication at study initiation. Exposure variables included respiratory event frequency, arousals, and oxygen desaturation. Cox models adjusted for body mass index, age, race, sex, change in body mass index, and continuous positive airway pressure device utilization. RESULTS: The adjusted analysis revealed that time spent with oxygen saturation less than 90 [hazards ratio (HR) 1.009], confidence interval (CI) 1.001-1.017, P = .02), respiratory arousals (HR 1.009, CI 1.003-1.015, P < 0.01) and total arousals (HR 1.006 CI 1.001-1.011 P = .02) were associated with an increased incidence of diabetes. Increases in mean nocturnal oxygen saturation were associated with decreased incidence of diabetes (HR 0.914 CI 0.857-0.975, P < .01) and prediabetes (HR 0.914 CI 0.857-0.975, P < .01). No significant relationships were demonstrated for apnea-hypopnea index (AHI), measures related to central apnea, Cheyne-Stokes respiration, periodic limb movements, or Epworth Sleepiness Scale score. CONCLUSIONS: There was no significant association of incident prediabetes or diabetes with AHI, the gold standard of sleep apnea severity. This study suggests that hypoxia may be a better predictor of glycemic outcomes than AHI in an obstructive sleep apnea population and may provide clues to the underlying mechanism(s) that link sleep-disordered breathing and its metabolic consequences. CITATION: Wojeck BS, Inzucchi SE, Qin L, Yaggi HK. Polysomnographic predictors of incident diabetes and pre-diabetes: an analysis of the DREAM study. J Clin Sleep Med. 2023;19(4):703-710.

Symptom Cluster Profiles Among Adults with Insomnia and Heart Failure.

OBJECTIVE/BACKGROUND: Both heart failure (HF) and insomnia are associated with high symptom burden that may be manifested in clustered symptoms. To date, studies of insomnia have focused only on its association with single symptoms. The purposes of this study were to: (1) describe daytime symptom cluster profiles in adults with insomnia and chronic HF; and (2) determine the associations between demographic and clinical characteristics, insomnia and sleep characteristics and membership in symptom cluster profiles. PARTICIPANTS: One hundred and ninety-five participants [M age 63.0 (SD12.8); 84 (43.1%) male; 148 (75.9%) New York Heart Association Class I/II] from the HeartSleep study (NCT0266038), a randomized controlled trial of the sustained effects of cognitive behavioral therapy for insomnia (CBT-I). METHODS: We analyzed baseline data, including daytime symptoms (fatigue, pain, anxiety, depression, dyspnea, sleepiness) and insomnia (Insomnia Severity Index), and sleep characteristics (Pittsburgh Sleep Quality Index, wrist actigraphy). We conducted latent class analysis to identify symptom cluster profiles, bivariate associations, and multinomial regression. RESULTS: We identified three daytime symptom cluster profiles, physical (N = 73 participants; 37.4%), emotional (N = 12; 5.6%), and all-high symptoms (N = 111; 56.4%). Body mass index, beta blockers, and insomnia severity were independently associated with membership in the all-high symptom profile, compared with the other symptom profile groups. CONCLUSIONS: Higher symptom burden is associated with more severe insomnia in people with stable HF. There is a need to understand whether treatment of insomnia improves symptom burden as reflected in transition from symptom cluster profiles reflecting higher to lower symptom burden.

Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial.

PURPOSE: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA. METHODS: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term "sleep apnea syndrome." A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA. RESULTS: Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m2; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28-0.96; P = 0.04). CONCLUSIONS: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA. CLINICALTRIALS: gov identifier: NCT01986881.

Insomnia with objective short sleep duration in community-living older persons: A multifactorial geriatric health condition.

BACKGROUND: Insomnia or poor sleep quality with objective short sleep duration (hereafter referred to as ISSD) has been identified as a high-risk phenotype among middle-aged persons. We evaluated the prevalence and clinical correlates of ISSD among community-living older persons. METHODS: In 3053 men from the Osteoporotic Fractures in Men Sleep Study (MrOS; average age 76.4 ± 5.5 years) and 3044 women from the Study of Osteoporotic Fractures (SOF; average age 83.6 ± 3.8 years), we evaluated the prevalence of ISSD (trouble getting to sleep within 30 minutes, waking up in the middle of the night or early morning, and/or taking a medication to help with sleep ≥3 times per week and actigraphy-estimated sleep duration <6 h). Using separate logistic regression models in men and women, we evaluated the cross-sectional associations between predisposing, precipitating, and perpetuating factors for ISSD, as compared with normal sleep (no insomnia and actigraphy-estimated sleep duration of 6-9 h). RESULTS: Overall, 20.6% of older men and 12.8% of older women had insomnia with short sleep duration. Multiple predisposing, precipitating, and perpetuating factors were cross-sectionally associated with ISSD in both men and women. In multivariable models that adjusted for predisposing factors (demographics, multimorbidity, obesity), precipitating (depression, anxiety, central nervous system-active medication use, restless legs syndrome) and perpetuating (napping, falls) factors were significantly associated with ISSD in men and women (adjusted odds ratios ranging 1.63-4.57). CONCLUSIONS: In this cross-sectional study of community-living older men and women, ISSD was common and associated with multiple predisposing, precipitating, and perpetuating factors, akin to a multifactorial geriatric health condition. Future work should examine causal pathways and determine whether the identified correlates represent modifiable risk factors.

PreScription DigitaL ThErapEutic for Patients with Insomnia (SLEEP-I): a protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04909229.

Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease.

AIMS: Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) often co-exist, yielding increased risk of cardiovascular (CV) complications including heart failure (HF). We assessed risk of cardiorenal outcomes, mortality and safety in patients with versus without COPD in the EMPA-REG OUTCOME trial. METHODS: Patients (n = 7,020) with T2DM and CV disease (CVD) were treated with empagliflozin (10 mg or 25 mg) or placebo. Cox regression was used to assess COPD subgroup (placebo only) associations with, and treatment effects of empagliflozin versus placebo on first hospitalization for HF (HHF), CV death, all-cause mortality, incident/worsening nephropathy, and all-cause hospitalization. RESULTS: At baseline, patients with COPD (n = 707) had more HF and used insulin more frequently than those without COPD. During follow-up in the placebo group, those with baseline COPD had increased risk of HHF (HR 2.15 [95% CI 1.32, 3.49]), HHF/CV death (1.60 [1.10, 2.33]), incident/worsening nephropathy (1.68 [1.26, 2.24]), all-cause hospitalization (1.44 [1.19, 1.74]) and all-cause death (1.60 [1.09, 2.35]) compared to those without COPD. Empagliflozin consistently reduced all clinical outcomes, irrespective of COPD status (interaction p-values 0.14 to 0.96), with a confirmed safety profile. CONCLUSIONS: In patients with T2DM and CVD, COPD increased the risk of mortality and cardiorenal outcomes, including HF. Empagliflozin consistently reduced these outcomes versus placebo regardless of COPD, suggesting that empagliflozin's benefits in patients with T2DM and CVD are not mitigated by the presence of COPD.

Self-reported and actigraphic short sleep duration in older adults.

STUDY OBJECTIVES: Persons > 65 years with short sleep duration (≤ 6 hours) are at risk for adverse outcomes, but the accuracy of self-reported sleep duration may be affected by reduced symptom awareness. We evaluated the performance characteristics of self-reported vs objectively measured sleep duration in this age group. METHODS: In 2,980 men from the Osteoporotic Fractures in Men Sleep Study and 2,855 women from the Study of Osteoporotic Fractures we examined the agreement and accuracy of self-reported vs actigraphy-measured short and normal (> 6 but < 9 hours) sleep duration. We evaluated associations of select factors (demographics; medical, physical, and neuropsychiatric conditions; medication and substance use; and sleep-related measures) with risk of false-negative (normal sleep duration by self-report but short sleep duration by actigraphy) and false-positive (short sleep duration by self-report and normal sleep duration by actigraphy) designations, respectively, using logistic regression. RESULTS: Average ages were 76.3 ± 5.5 and 83.5 ± 3.7 years in men and women, respectively. There was poor agreement between self-reported and actigraphic sleep duration (kappa ≤ 0.24). False negatives occurred in nearly half and false positives in over a quarter of older persons. In multivariable models in men and women, false negatives were independently associated with obesity, daytime sleepiness, and napping, while false positives were significantly lower with obesity. CONCLUSIONS: Under- and overreporting of short sleep is common among older persons. Reliance on self-report may lead to missed opportunities to prevent adverse outcomes or unnecessary interventions. Self-reported sleep duration should be objectively confirmed when evaluating the effect of sleep duration on health outcomes. CITATION: Miner B, Stone KL, Zeitzer JM, et al. Self-reported and actigraphic short sleep duration in older adults. J Clin Sleep Med. 2022;18(2):403-413.

Cognitive behavioral therapy for insomnia has sustained effects on insomnia, fatigue, and function among people with chronic heart failure and insomnia: the HeartSleep Study.

STUDY OBJECTIVES: Insomnia is common among adults with chronic heart failure (HF) and associated with daytime symptoms and decrements in function. The purpose of this randomized controlled trial (RCT) was to evaluate the sustained effects over one year of CBT-I (Healthy Sleep: HS) compared with HF self-management education (Healthy Hearts; attention control: HH) on insomnia severity, sleep characteristics, symptoms, and function among people with stable HF. The primary outcomes were insomnia severity, actigraph-recorded sleep efficiency, and fatigue. METHODS: We randomized adults with stable HF with preserved or reduced ejection fraction who had at least mild insomnia (Insomnia severity index >7) in groups to HS or HH (4 sessions/8 weeks). We obtained wrist actigraphy and measured insomnia severity, self-reported sleep characteristics, symptoms (fatigue, excessive daytime sleepiness, anxiety, depression), and six-minute walk distance at baseline, within one month of treatment, and at 6 and 12 months. We used general linear mixed models (GLMM) and generalized estimating equations (GEE) to evaluate the effects. RESULTS: The sample included 175 participants (M age = 63 ± 12.9 years; 43% women; 18% Black; 68% New York Heart Association Class II or II; 33%; LVEF < 45%) randomized to HS (n = 91) or HH (n = 84). HS had sustained effects on insomnia severity, sleep quality, self-reported sleep latency and efficiency, fatigue, excessive daytime sleepiness, and six-minute walk distance at 12 months. CONCLUSIONS: CBT-I produced sustained improvements in insomnia, fatigue, daytime sleepiness, and objectively measured physical function among adults with chronic HF, compared with a robust HF self-management program that included sleep hygiene education. CLINICAL TRIAL INFORMATION: Insomnia Self-Management in Heart Failure; https://clinicaltrials.gov/ct2/show/NCT02660385; NCT02660385.

A SAS macro for modelling periodic data using cosinor analysis.

BACKGROUND AND OBJECTIVE: Cosinor analysis, developed by Franz Hallberg and colleagues in the 1960s, allows for the fitting of a cosine curve to data of a known period. Cosinor analysis is frequently used in the analysis of biological rhythm data. While software exists to perform these analyses, we are not aware of any published SAS procedures or macros which would facilitate them. METHODS: To meet this gap, we herein describe SAS macros which perform cosinor analyses that assume either normally or gamma distributed outcomes and fixed period. The macros can 1) produce datasets with cosinor parameters including acrophase, mesor, amplitude, nadir and test for rhythmicity 2) output datasets with fitted and observed values from the model, and 3) plot the resulting curve and underlying data. RESULTS: We demonstrate the use of these macros with data from our research on circadian rhythms of heart rate and sleep in critically ill patients. CONCLUSIONS: Cosinor analysis provides a parsimonious and intuitive set of estimates to summarize periodic data. We are hopeful that the publication of our macro will allow a wider spectrum of users to avail themselves of this technique.

Polysomnographic Phenotypes of Obstructive Sleep Apnea and Incident Type 2 Diabetes: Results from the DREAM Study.

Rationale: Obstructive sleep apnea (OSA) is associated with cardiovascular disease and incident type 2 diabetes (T2DM). Seven OSA phenotypes, labeled on the basis of their most distinguishing polysomnographic features, have been shown to be differentially associated with incident cardiovascular disease. However, little is known about the relevance of polysomnographic phenotypes for the risk of T2DM. Objectives: To assess whether polysomnographic phenotypes are associated with incident T2DM and to compare the predictive value of baseline polysomnographic phenotypes with the Apnea-Hypopnea Index (AHI) for T2DM. Methods: The study included 840 individuals without baseline diabetes from a multisite observational U.S. veteran cohort who underwent OSA evaluation between 2000 and 2004, with follow-up through 2012. The primary outcome was incident T2DM, defined as no diagnosis at baseline and a new physician diagnosis confirmed by fasting blood glucose >126 mg/dL during follow-up. Relationships between the seven polysomnographic phenotypes (1. mild, 2. periodic limb movements of sleep [PLMS], 3. non-rapid eye movement and poor sleep, 4. rapid eye movement and hypoxia, 5. hypopnea and hypoxia, 6. arousal and poor sleep, and 7. combined severe) and incident T2DM were investigated using Cox proportional hazards regression and competing risk regression models with and without adjustment for baseline covariates. Likelihood ratio tests were conducted to compare the predictive value of the phenotypes with the AHI. Results: During a median follow-up period of 61 months, 122 (14.5%) patients developed incident T2DM. After adjustment for baseline sociodemographics, fasting blood glucose, body mass index, comorbidities, and behavioral risk factors, hazard ratios among persons with "hypopnea and hypoxia" and "PLMS" phenotypes as compared with persons with "mild" phenotype were 3.18 (95% confidence interval [CI], 1.53-6.61] and 2.26 (95% CI, 1.06-4.83) for incident T2DM, respectively. Mild OSA (5 ⩽ AHI < 15) (vs. no OSA) was directly associated with incident T2DM in both unadjusted and multivariable-adjusted regression models. The addition of polysomnographic phenotypes, but not AHI, to known T2DM risk factors greatly improved the predictive value of the computed prediction model. Conclusions: Polysomnographic phenotypes "hypopnea and hypoxia" and "PLMS" independently predict risk of T2DM among a predominantly male veteran population. Polysomnographic phenotypes improved T2DM risk prediction comared with the use of AHI.