Citations

Background The prevalence of excessive daytime sleepiness (EDS) in the general population is reported to be 9 to 28 percent. Various social and biological factors have been reported to contribute to the development of EDS, such as cardiovascular disease, metabolic disorders as well as socioeconomic status. Medically, EDS is associated with poorer prognosis in patients with sleep disorders. However, whether sleepiness is an independent negative prognostic indicator in patients without sleep apnea is poorly understood. Objective To evaluate the relationship between self‐reported excessive daytime sleepiness (assessed by Epworth Sleepiness Scale) and the risk of all‐cause mortality in patients without obstructive sleep apnea (OSA). Methods We performed a retrospective cohort study in a large registry of patients seen at the Mayo Clinic Center for Sleep Medicine between November 17 th , 2009 and April 15 th , 2017. All patients received a diagnostic polysomnography and had completed Epworth Sleepiness Scale (ESS). The primary outcome of all‐cause mortality risk was computed using the Kaplan‐Meier analysis and Cox‐proportional hazard model with age, sex, body mass index (BMI), baseline comorbidities and sleep measurements as confounders. Results A total of 2746 non‐OSA patients were identified. The overall median age (IQR) was computed as 53 (40, 63) with 45% of patients identifying as males. The median follow‐up time was approximately 2.3 years. In a univariate analysis, daytime sleepiness was associated with the female sex, younger age and higher BMI. No significant differences were observed in vascular related diseases between sleepy and non‐sleepy patients. EDS was not significantly associated with all‐cause mortality with an adjusted hazard ratio of 1.23 (95% CI 0.86, 1.76; p =0.257). In addition, there was no significant association of EDS and the risk of all‐cause mortality even after stratifying by sex, age and BMI in non‐OSA patients. Conclusion EDS is not associated with all‐cause mortality in non‐OSA patients. Further prospective studies are needed to confirm this finding. Support or Funding Information This research was supported by NIH HL65176 and NIH HL114024. Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. image Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Treatment resistant restless legs syndrome (RLS) in the setting of psychiatric comorbidities can be difficult to manage. Our patient is a 69-year-old Caucasian gentleman with bipolar disorder type I, unspecified anxiety disorder, obstructive sleep apnea (OSA), and treatment-refractory RLS. At initial presentation, the patient’s prescribed medication regimen included fluoxetine 40 mg daily, gabapentin 800 mg in the morning and 3200 mg at bedtime, pramipexole 0.375 mg daily, lamotrigine 200 mg daily, trazodone 200 mg at bedtime, and temazepam 15 to 30 mg as needed for insomnia and RLS. Over the course of nearly 4 years, treatment interventions for this patient’s RLS included: cognitive behavioral therapy for insomnia, discontinuation of exacerbating medications, switching dopamine agonists, use of pregabalin and iron supplement. This report demonstrates a challenging case of RLS in the setting of psychiatric comorbidities, development of augmentation, and polypharmacy.

Abstract Introduction Sleep disruption is common in patients with alcohol use disorders (AUD) and major depressive disorders (MDD). Our understanding of the differences in the rates of sleep disturbance and overall sleep duration in patients with AUD, MDD, and comorbid AUD and MDD is limited. Furthermore, it is unknown whether there is variation in demographic and clinical characteristics associated with sleep disturbance and duration in these diagnostic groups. Methods This study utilized data from the UK Biobank (UKB). Depression status was determined based on review of International Classification of Diseases (ICD) codes and health records. AUD status was based on AUDIT scores (score ≥8 was defined as AUD) and sleep disturbance was evaluated utilizing a self-reported questionnaire. The sample was categorized into those with MDD alone (MDD+/AUD-)(n=18,154), AUD alone (MDD-/AUD+)(n=6123), both (MDD+/AUD+)(n=9027), and controls with neither (MDD-/AUD-)(n=27,573). We used generalized linear models (GLMs) to compare rates of sleep disruption and duration among the groups and determine the clinical predictors of sleep disturbance/duration in the four groups as well as test whether these factors differed among the groups. Results The prevalence of sleep disturbance in the control sample (MDD-/AUD-) was 26.4% and the self-reported sleep duration in this sample was 7.209±0.919. Subjects with AUD and/or MDD had greater rates of sleep disturbance and shorter sleep duration. Among the different diagnostic categories, the prevalence of sleep disturbance was highest in subjects with MDD+/AUD+ (36.5%) followed by those with MDD+/AUD- (35.6%) and MDD-/AUD+ (27.9%)(all p<0.0001). Similarly, the sleep duration was shortest in subjects with MDD+/AUD+ (7.143±1.016), followed by MDD+/AUD- (7.158±1.050) and by MDD-/AUD+ (7.202±0.891)(all p<0.0001). Subjects with sleep disturbance were more likely to be older, female, and with higher body mass index, Townsend deprivation index, and neuroticism scores across all four groups (all p<0.05). Conclusion In a large population-based cohort, MDD with and without comorbid AUD was associated with greater rates of sleep disturbance and shorter sleep duration than AUD alone. The clinical and demographic factors associated with sleep disturbance did not differ in these diagnostic categories, indicating possible similar underlying risk factors. Support (if any) NA

Abstract Introduction Sleep disruption and reduced sleep duration are potential triggers and also core symptoms of a manic episode. Our understanding of how sleep duration changes during the course of a manic episode and its potential association with symptom improvement is limited. We examined the natural course of sleep duration and its association with time to discharge and other clinical and demographic factors in patients with mania. Methods This was a retrospective study conducted in patients admitted to an acute care psychiatric unit with a manic episode. Sleep duration was determined based on observer report as logged by nursing staff. Sleep duration at admission and discharge were determined by averaging the total sleep time on day 2/3 of hospitalization and day 3/2 preceding discharge date. We obtained data on possible confounders including antipsychotic (chlorpromazine equivalents), benzodiazepine (diazepam equivalents) and other hypnotic medication doses administered at admission and discharge. We examined the associations between the change in sleep duration from admission to discharge with length of hospitalization and other clinical and demographic characteristics. Results The sample consisted of 35 patients (54.3% male) aged 32 ± 9.96 years with an average length of hospitalization of 20.63 ± 18.62 days. The mean sleep duration on admission was 6.23 ± 1.77 hours and was 7.45 ± 1.49 hours on discharge, with a mean change of 1.23 ± 1.93 hours. The change in sleep duration was positively correlated with length of hospitalization (r=0.42; p=0.01). Other clinical factors including benzodiazepine or antipsychotic dose on admission, age, sex, and use of mood stabilizers were not correlated with the change in sleep duration. Conclusion There was a substantial improvement in the total sleep duration in patients with mania over the course of hospitalization. Overall, the change in sleep duration was only correlated to the length of stay and did not appear to be impacted by other clinical and demographic characteristics. Support (if any):

Opioid use disorder (OUD) is a cause of significant morbidity and mortality in the United States. Although efforts are being made to limit access to prescription opioids, the use of heroin and synthetic opioids as well as death due to opioid overdose has increased. Medication-assisted treatment (MAT) is the pairing of psychosocial intervention with a Food and Drug Administration (FDA)–approved medication (methadone, buprenorphine plus naltrexone) to treat OUD. MAT has resulted in reductions in overdose deaths, criminal activity, and infectious disease transmission. Access to MAT in rural areas is limited by shortages of addiction medicine-trained providers, lack of access to comprehensive addiction programs, transportation, and cost-related issues. Rural physicians express concern about lack of mentorship and drug diversion as reasons to avoid MAT. The prescribing of MAT with buprenorphine requires a Drug Enforcement Agency (DEA) waiver that can easily be obtained by Family Medicine providers. MAT can be incorporated into the outpatient practice, where patient follow-up rates and number needed to treat to effect change are similar to that of other chronic medical conditions. We describe a case of opioid overdose and a suggested protocol for the induction of MAT with buprenorphine/naloxone (Suboxone) for OUD in a rural family medicine outpatient practice. Treatment access is facilitated by utilizing the protocol, allowing office staff work to the extent allowed by their licensure, promoting teamwork and minimizing physician time commitment. We conclude that improved access to MAT can be accomplished in a rural family medicine outpatient clinic by staff that support and mentor one another through use of a MAT protocol.

Abstract Introduction Patients presenting with excessive sleepiness are frequently on antidepressant medication(s). While practice parameters recommend discontinuation of antidepressants prior to multiple sleep latency testing (MSLT), data examining the impact of tapering these medications on MSLT results are limited. Methods Adult patients who underwent MSLT at Mayo Clinic Rochester, Minnesota, between 2014-2018 were included. Clinical and demographic characteristics, medications, including use of rapid eye movement suppressing antidepressants (REMS-AD) at assessment and during testing, actigraphy and polysomnography data were manually abstracted. The difference in number of sleep-onset rapid eye movement periods (SOREMS), proportion with ≥2 SOREMS and mean sleep latency (MSL) in patients who were on REMS-AD and discontinued prior to testing versus those who remained on REMS-AD were examined. At our center, all antidepressants are discontinued 2 weeks prior to MSLT wherever feasible; fluoxetine is stopped 4 weeks prior. Regression analyses accounting for demographic, clinical and other medication-related confounders were performed. Results A total of 502 patients (age=38.18±15.90 years; 67% female) underwent MSLT; 178 (35%) were on REMS-AD at the time of assessment. REMS-AD were discontinued prior to testing in 121/178 (70%) patients. Patients tapered off REMS-AD were more likely to have ≥2 SOREMS (OR-12.20; 95%CI=1.60-92.94) compared to patients who remained on REMS-AD at the time of the MSLT. They also had shorter MSL (8.77±0.46 vs 10.21±0.28; p>0.009) and higher odds of having ≥2 SOREMS (OR=2.22; 95%CI=1.23-3.98) compared to patients not on REMS-AD at initial assessment. These differences persisted after regression analyses accounting for confounders. Conclusion Patients who taper off REMS-AD prior to MSLT are more likely to demonstrate ≥2SOREMs and have a shorter MSL. Pending further prospective investigations, clinicians should preferably withdraw REMs-AD before an MSLT. If this is not done, the test interpretation should include a statement regarding the potential effect of the drugs on the results. Support None

Abstract Introduction Sleep disordered breathing (SDB) is associated with adverse cardiovascular outcomes and decreased cardiorespiratory fitness (CRF). The risk of long-term major adverse cardiovascular events (MACE) when SDB and decreased CRF co-occur has not been determined. Methods We included consecutive patients that underwent a symptom-limited cardiopulmonary exercise test followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-severe SDB (apnea/hypopnea index ≥15/hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO2). MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke/transient ischemic attack (TIA) and death. Cox-proportional hazard models adjusting for factors known to influence CRF and MACE were constructed. Results Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5-10.3 years). After adjusting for age, sex, beta-blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking and positive airway pressure (PAP) usage, decreased CRF alone (HR=1.91, 95%CI=1.15-3.18, p=0.012), but not SDB alone (HR=1.26, 95%CI=0.75-2.13, p=0.389) was associated with increased risk of MACE. Those with SDB and decreased CRF had increased risk of MACE compared to patients with decreased CRF alone (HR=1.85, 95%CI=1.21-2.84, p<0.005) after accounting for these confounders; the risk was attenuated after additionally adjusting for adequate adherence to PAP (HR=1.85, 95%CI=0.99-3.05, p=0.05). Conclusion The incidence of MACE, including mortality, was high in this sample. Moderate-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of including CRF in the risk assessment of patients with SDB, and conversely, that of screening for SDB in patients with low peak VO2. Support None.