Citations

Abstract Background Up to eight percent of pregnant women have pre-eclampsia. These women have an increased risk of future ischemic heart and cerebral disease. This warrants early cardiovascular risk management in early disease stages. This meta-analysis determines how the prevalence of subclinical atherosclerosis in women after pre-eclamptic compared to non-pre-eclamptic pregnancies changes over time. Methods A systematic search was used. Studies reporting the prevalence of systemic atherosclerosis using ultrasound or computed tomography in formerly pre-eclamptic and non-pre-eclamptic women were included. A random-effects meta-analysis provided overall odds ratio’s (OR (95% confidence interval (CI)) for the association between pre-eclampsia and the prevalence of atherosclerosis. Results Eleven articles could be included with a total of 13,217 participants. Maternal age ranged from 33 to 60 years. Within this age period, pooled OR of developing atherosclerosis after pre-eclampsia was 1.57 (95%CI 1.39-1.78). The pooled odds of developing atherosclerotic plaque after a pre-eclamptic versus a non-pre-eclamptic pregnancy increased gradually with age. The odds ratio was not significantly different in the 30-39 age group (OR 0.64 (95%CI 0.10-4.15)), but there was a statistically significantly increased odds of finding an atherosclerotic plaque in the 40-49 (OR 1.59 (95%CI 1.34-1.89)) and 50-60 age groups (OR 2.00 (95%CI 1.30-3.08)) after pre-eclamptic pregnancies compared to non-pre-eclamptic pregnancies. Conclusions Formerly pre-eclamptic women have earlier and more frequent atherosclerosis and occurs ten years earlier than in non-pre-eclamptic women. Targeted prevention strategies are required to prevent premature cardiovascular disease morbidity and mortality in formerly pre-eclamptic women.

Abstract Introduction Solid organ transplant recipients experience high rates of cognitive impairment; however, little is known about what modifiable factors contribute to cognitive impairment after transplantation, limiting evidence-based treatment options. Insomnia is a sleep disorder that is associated with poor cognitive functioning in healthy adults and is amenable to interventions, but the relationship between insomnia and cognitive impairment after organ transplantation has not been explored. The purpose of this study was to identify relationships between insomnia, sleep characteristics, and perceived cognitive function after organ transplantation. Methods We conducted a descriptive, cross-sectional study of adult (>18 years) transplant recipients. We used the Insomnia Severity Index to measure insomnia, 10 days of continuous wrist actigraphy (Ambulatory Monitoring Inc. MicroMotionlogger) to measure sleep characteristics, and the PROMIS Cognitive Function to elicit perceived cognitive function. Descriptive statistics, Spearman’s Rho correlations, and Pearson’s correlations were used to describe relationships. Results We enrolled 34 participants [Mean age 62.5 years (SD 10.7), 64.7% (n=22) female, 85.3% (n=29) white, 17 liver/9 heart/8 kidney, average time since transplant 4.8 years (SD 4.2)]. 73.3% had clinically significant insomnia [mean ISI: 12.9 (SD 6.9)]. Sleep characteristics were obtained using actigraphy (mean duration: 7.03 hours [SD 1.28], onset latency: 9.16 min [SD 4.90], efficiency: 89.49% [SD 8.96], wake after sleep onset: 49.61 [SD 37.37]). Perceived cognitive function for the sample was worse than that of the general population, with a mean T-score of 45.21 (SD 11.44). Lower perceived cognitive function scores were significantly associated with younger age (rs = -.416, p=.016) and shorter time since transplant (rs =-.386, p=.024). Longer wake after sleep onset (rs =.347, p=.048) and lower sleep efficiency (rs=-.358, p=.041) were associated with lower perceived cognitive function. Lower perceived cognitive function was strongly associated with higher insomnia severity scores (r=.817, p=<.001). Conclusion Insomnia was common in our sample of transplant recipients and was strongly correlated with worse perceived cognitive function. Future research should incorporate objective measures of cognitive functioning and should consider insomnia treatment as a potential intervention to promote optimal cognitive functioning after organ transplantation. Support (if any) Mayo Clinic Center for Clinical and Translational Science.

Abstract Introduction Large language models (LLMs), such as ChatGPT-4, have demonstrated promising potential as diagnostic tools across various medical disciplines. In sleep medicine, artificial intelligence tools are already used to analyze physiological sleep data and are being studied for their potential in phenotyping, endotyping, and predicting treatment responses. However, the effectiveness of LLMs in accurately diagnosing sleep disorders based on clinical history has not yet been studied. This study evaluates ChatGPT-4’s diagnostic performance using clinical vignettes. Methods Nineteen clinical cases were selected from the Case Book of Sleep Medicine, Third Edition (AASM, 2019). Each case included patient history, examination findings, and test results. The vignettes were input into ChatGPT-4 using the following standardized prompt: “Based on the provided case details, generate the top 5 differential diagnoses and identify the most likely final diagnosis: (copy and paste clinical vignette).” The model was tasked with generating both differential diagnoses and a final diagnosis for each case. The AI’s results were compared to reference diagnoses from the case book. Differential diagnoses were measured as the number of matches, and accuracy was reported as a percentage. Final diagnoses were scored as 0 (no match), 1 (partial match), or 2 (full match). Results The mean number of AI-generated differential diagnoses matching the AASM case differential diagnoses was 2.79 ± 0.71 (95% CI: 2.45–3.13). The mean accuracy percentage for differential diagnoses was 63.27% ± 15.61% (95% CI: 55.75%–70.79%), with scores ranging from 33.33% to 100%. For final diagnoses, ChatGPT-4 scored a total of 30 out of a possible 38, with a mean score was 1.58 ± 0.61 (95% CI: 1.29–1.87) out of 2, with 74% of cases achieving a full match. Performance was higher in cases with fewer differential diagnoses, whereas accuracy decreased in more complex cases. Conclusion ChatGPT-4 showed moderate to high accuracy in generating both differential and final diagnoses for sleep disorders. These findings suggest that AI could become a valuable clinical decision-support tool in sleep medicine. However, its inconsistent performance in complex cases highlights the need for further refinement and clinical testing. Support (if any)

Background: Major League Baseball (MLB) recently instituted a combine for their prospective players. Purpose/Hypothesis: The purpose of this study was to report initial epidemiological findings for both physical examination and imaging findings for the MLB Combine. It was hypothesized that most players would have no significant abnormal physical examination findings, but most would have abnormal findings on their shoulder and elbow magnetic resonance imaging (MRI) scans. Study Design: Descriptive epidemiology study. Methods: All players who attended the 2023 MLB Combine were included. History was taken and physical examination was performed by an MLB team physician, and MRI of the shoulder, elbow, cervical spine, and lumbar spine was performed on all players and read by 1 of 2 musculoskeletal radiologists. Physical examination notes and imaging reports were reviewed by the authors and recorded. Data were analyzed separately for pitchers and position players. Results: Overall, 219 players (112 pitchers [51%], 107 position players [49%]) were included. The mean age was 20.4 ± 1.5 years. The majority of players (95%) had no current pain or limitations; 54 players (25%) had a history of previous surgery. For pitchers, 18% underwent previous elbow surgery. With regard to MRI, >80% of pitchers had some abnormality within their ulnar collateral ligament (UCL), the majority of which was UCL scarring/remodeling. 70% of pitchers and 60% of position players had evidence of an olecranon osteophyte. Increased signal within the ulnar nerve was common in pitchers (40%) but rare in position players (4%). For the shoulder, 95% of pitchers and 93% of position players had some rotator cuff abnormality (often tendinosis within the supraspinatus and infraspinatus muscles). Also, 75% of pitchers had MRI evidence of a superior labrum anterior to posterior (SLAP) tear, while 24% of position players demonstrated this. Lumbar spine MRI showed that 47% of position players had a disk protrusion and 46% had a previous pars fracture. Conclusion: Most baseball players who participated in the 2023 MLB Combine had MRI evidence of rotator cuff abnormalities, and many showed evidence of an olecranon osteophyte. Eighteen percent of pitchers had a previous history of elbow surgery. The majority of pitchers had some abnormality within their UCL and evidence of a SLAP tear on MRI scans.

Abstract Introduction The majority of adults with inflammatory bowel disease (IBD) experience disability which is not fully explained by disease activity. Up to 80% of adults with IBD experience poor sleep health, which is associated with disability in other populations; however, the relationship between disability and sleep health among patients with IBD is largely unexamined. The purpose of this study was to compare the sleep health characteristics of those with and without IBD-related disability. Methods We recruited adults (18 to 59 years old) with IBD from a single academic medical center from 2022 to 2024. We measured disease activity using the Manitoba IBD Index and sleep using the PROMIS Sleep Disturbance and PROMIS Sleep-Related Impairment scales, the Insomnia Severity Index, and 14 days of wrist-worn actigraphy (Phillips Spectrum Plus, Phillips Respironics). We asked participants how many days they missed or had at least 50% reduced productivity in paid work or household work or missed leisure activities in the last 3 months related to their IBD. Disability was defined as missing six or more day over three months. We conducted bivariate analyses and logistic regressions to study associations. Results Among 83 adults with IBD [mean age = 40.4 years (SD 10.7), 59 (71.1%) were female, 56 (71.1%) had Crohn’s disease], and 49 (62.0%) had IBD-related disability. Patients with disability had more severe sleep disturbance (56.4 vs. 51.0, p <.001), sleep-related impairment (58.3 vs 50.3, p <.001), more severe insomnia (12.7 vs. 9.4, p =.029), and actigraph-measured higher wake after sleep onset (41.6 minutes vs. 34.0 minutes, p = 0.012) and lower sleep efficiency (85.1% vs. 87.9%, p = 0.032) compared to those without disability. After controlling for age and disease activity, sleep-related impairment (OR = 1.1, 95% CI 1.03, 1.15) was independently associated with disability. Conclusion Patients with IBD-related disability experience poor sleep health. Sleep related daytime impairment uniquely contributed to disability when controlling for disease activity. Sleep interventions need to be tested in adults with IBD to determine if they are effective at addressing disability in this population. Support (if any) Mayo Clinic Bonner Fund

Abstract Introduction Tizanidine is an alpha-2 receptor adrenergic agonist employed for treatment of musculoskeletal pain and muscle spasticity. Drowsiness, xerostomia, and, less frequently, sleep disturbance are notable side effects. Central sleep apnea (CSA) occurs in patients taking other alpha-2 receptor agonists such as clonidine but the frequency of CSA among users of tizanidine is less well-known. Rarer still is the presence of central apneic episodes during wakefulness in patients without heart failure who have an intact brainstem and are not taking opioids or benzodiazepines. We report a case of a patient with central apneic episodes during wakefulness in the setting of tizanidine use. Report of case A 60-year-old white male was referred to our sleep center for sleep apnea. He was previously diagnosed with severe obstructive sleep apnea (apnea-hypopnea index of 104 events per hour) but was not adherent to continuous positive airway pressure (CPAP) due to a previous head injury which made use of CPAP straps intolerably painful. Thus, he had undergone a modified uvulopalatopharyngoplasty 3 months prior to evaluation. Despite UPPP he continued to have excessive daytime sleepiness. A repeat polysomnogram revealed frequent central apneic episodes during periods of wakefulness that did not persist after sleep onset. The patient had taken his nightly tizanidine 8 mg prior to testing. Echocardiogram prior to testing showed mild diastolic dysfunction and brain magnetic resonance imaging was unremarkable. A polysomnogram was repeated 1 month later, this time with tizanidine held for 1 week prior to testing. Wake-onset central apneic episodes had resolved without any other changes in medication or health status. Conclusion Certain medications such as opioids, benzodiazepines, and baclofen are known to induce CSA. However, to the best of our knowledge this is the first case of a commonly prescribed alpha-2 agonist implicated in the development of wake-onset central apneic episodes. More study is needed to elucidate the impact of tizanidine on ventilatory function in the wake and sleep states and whether similar effects may occur among other centrally acting medications. Support (if any)

Abstract Introduction Restless Legs Syndrome (RLS) affects up to 3% of the adult population in the United States, with approximately one-third of these individuals experiencing medically refractory disease. Historically, treatments for RLS have included iron replacement, dopamine agonists, and alpha-2-delta ligands. However, dopamine agonists are often associated with augmentation, a phenomenon in which RLS symptoms worsen. This includes increased severity, earlier onset, spread of symptoms to other parts of the body, and the need for higher doses of medications. Over the past decade, the use of opioid therapy for refractory RLS has become more widely accepted. Buprenorphine-naloxone, a combination medication, includes buprenorphine, a partial agonist at the mu-opioid receptor, which is less likely to cause respiratory depression, overdose, or euphoria compared to full agonists. Naloxone, an opioid antagonist, is included to deter misuse. Here, we share the treatment responses of three patients with refractory RLS who were treated with buprenorphine-naloxone. Report of case Pre- and post-treatment IRLS were compared in three Sleep Medicine patients (two females, aged 70, and one male, aged 72) on therapeutic doses of buprenorphine-naloxone. Patient charts were reviewed for medication side effects. Previous treatments included dopamine agonists, alpha-2-delta ligands, iron supplementation, benzodiazepines, methadone, and melatonin. Pre-treatment IRLS scores were 13, 13, and 24, classified as moderate to severe. The formulations used included buprenorphine-naloxone 2-0.5 mg sublingual tablets and buprenorphine-naloxone 2-0.5 mg 1/8 films. Therapeutic daily doses of buprenorphine-naloxone ranged from 7.5 to 60 morphine milligram equivalents (MME) per day. Post-treatment IRLS scores were 0, 2, and 3, representing an average reduction of over 15 points on the IRLS. Average time between pre- and post-treatment IRLS was 29 months. Side effects were reported by one patient, including fatigue, depressive symptoms, and reflux, but none of the patients experienced side effects that limited the use of the medication. Conclusion In this case series, we demonstrate the positive impact of buprenorphine-naloxone in managing refractory RLS, as evidenced by substantial reductions in IRLS scores from moderate to severe levels. We hope to encourage clinicians to consider buprenorphine-naloxone as an effective and well-tolerated treatment option for patients with refractory RLS. Support (if any)

Abstract Introduction Moyamoya is characterized by idiopathic, progressive, large intracranial arterial steno-occlusion, affecting the anterior circulation of the brain. Common presentations include strokes, seizures, and headaches, which have been associated with poor sleep quality and sleep disorders in the general population. However, to our knowledge, sleep quality has not been previously investigated in Moyamoya disease. The aim of this study was to characterize self-reported sleep quality, sleepiness, sleep disorder diagnoses in patients with Moyamoya syndrome, and to explore possible association between sleep disturbance and quality of life in these patients. Methods We analyzed consecutive patients with Moyamoya evaluated at our institution who completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). We also abstracted the Patient-Reported Outcomes Measurement Information System (PROMIS) to measure person-centered physical, mental and social wellbeing. Results We studied 23 patients with mean age 41.8 ± 12.1 years old having disease duration of 3 ± 4.4 years. 15 (65.2%) had ischemic strokes. Mean total PSQI score was 6.9 ± 2.9, and 17 (73.9%) had poor sleep quality (PSQI>5). Mean sleep efficiency was reduced at 80 ± 17%. Although Median ESS was 6 (IQR 3.25 – 8), most patients (91.3%) reported at least mild daytime dysfunction (Component 7≥1). Mean PSQI component scores (0 – 3 severity, 3 is worse) were 1.29 ± 0.62 (subjective quality), 1.1 ± 0.73 (sleep latency), 1.04 ± 0.83 (sleep duration), 0.87 ± 1.01 (sleep efficiency), 1.22 ± 0.52 (sleep disturbances), 0.3 ± 0.88 (sleep medication), and 1.1 ± 0.52 (daytime dysfunction). The total PSQI score was positively correlated with PROMIS score (r=0.47, p=0.044). Only one patient was diagnosed with obstructive sleep apnea and three with chronic insomnia. Conclusion Poor sleep quality appears to be a frequent problem in patients with Moyamoya disease. Sleep disturbance severity was similar to previous findings in clinical stroke populations. The apparent mismatch between subjective sleep disturbance and sleep disorder diagnoses suggest that sleep disorders are likely underdiagnosed in Moyamoya patients. The relationship between PSQI and PROMIS scores suggests that sleep disturbance may significantly affect quality of life in these patients. Support (if any)

Abstract Introduction Comparing sleep and rest-activity rhythms (RARs) across the spectrum of cognitive aging can reveal novel risk factors and potential mechanisms underlying dementia disorders. However, our current understanding is restricted by differences in sleep measurement, limited longitudinal data, and heterogeneous cognitive aging processes. We aimed to determine (1) which sleep/RAR features exhibit meaningful changes within three distinct cognitive pathways; and (2) which sleep/RAR features differ between cognitive aging pathways prior to and after the onset of mild cognitive impairment (MCI) and/or dementia. Methods Longitudinal self-reported sleep and actigraphy data were obtained from 1,449 participants in the Rush Memory and Aging Project (mean age= 81.2±7.1 years, 75.2% female, 5.2% Black, 94.8% White). We applied flexible cubic spline models to quantify differences in the levels and trajectories of sleep amount (self-reported duration; actigraphy rest interval length and alpha), regularity (actigraphy interdaily stability, intradaily variability, and midpoint standard deviation), and timing (self-reported midpoint; actigraphy midpoint and acrophase) within and between three cognitive aging pathways over 12 years: Normal Cognitive Aging (‘Normal’), Progression to MCI (‘Stable MCI’), and Progression to Dementia (‘Dementia’). Models were adjusted for key sociodemographic and health variables. Results Sleep amount was lowest in the Dementia pathway prior to MCI or dementia, but increased with age, most rapidly following dementia. The greatest effect was observed in self-reported duration (standardized mean change, d[95%CI]=0.912 [0.47, 1.36]. Regularity declined across all pathways, most rapidly after cognitive diagnoses, with the largest increases in intradaily variability occurring among the Stable MCI (d=0.97 [0.70, 1.23]) and Dementia paths (d=1.11 [0.84, 1.38). Shifts toward earlier sleep timing were observed in actigraphy measures across all three pathways (-0.54≤d≤-0.31). Conclusion Shorter sleep amount in cognitively healthy older adults may be a risk factor or prodromal indicator of dementia, while longer sleep amounts and decreasing regularity following dementia may reflect neurodegeneration. Advances in sleep timing may be less useful as a clinical indicator of future cognitive impairment or decline. Differences between self-reported and actigraphy-measured sleep/RAR outcomes may reflect distinct underlying mechanisms, warranting further research. Support (if any) NIH: T32HL082610, RF1AG056331, R01AG052488, R01AG071638, RF1AG070436, R01AG17917

Abstract Introduction Sleep apnea impacts 50-70% of patients following stroke. Treatment of obstructive sleep apnea (OSA) in patients with stroke using continuous positive airway pressure (CPAP) has been recommended in recent American Heart Association/American Stroke Association guidelines. However, stroke patients poorly tolerate CPAP and often remain untreated. There is a paucity of data regarding alternative treatments such as oral appliance therapy (OAT) in stroke patients. We hypothesized that oral appliance therapy would be an efficacious option in the treatment of OSA in stroke patients, defined as a ≥50% reduction in apnea-hypopnea index (AHI) or oxygen desaturation index (ODI) or reduction in total AHI or ODI to < 10/h. Methods We performed a retrospective review of patients with OSA treated with OAT at our institution and had a history of stroke prior to receiving the oral appliance. Chart abstraction included demographic data, stroke type, sleep apnea diagnostic data, and efficacy data. Efficacy data included repeat sleep studies, overnight oximetry, patient reported outcomes, and subjective benefit, as available. Results 23 patients (52% female, mean age 63) were identified with a history of stroke prior to use of OAT for OSA. Baseline parameters (mean, SD) included BMI (30.8, 4.2), AHI (15.0, 10.6), and Epworth Sleepiness Scale (ESS) (9.3, 5.4). Post-treatment parameters included (mean, SD) BMI (30.1, 4.2), AHI (12.4, 12.0), and ESS (6.5, 4.0). 12 patients had both baseline and follow-up sleep studies performed which met criteria for AHI efficacy of OAT in 7 of 12 (58%). Wilcoxon signed rank exact test demonstrated improvement in median AHI of 9.3 (0.40-17.6, p< 0.05) among these 12 patients. 2 of 3 (67%) patients with overnight oximetry follow-up met criteria for ODI efficacy of OAT. Of 8 patients with only subjective follow-up, 6 (75%) reported subjective improvement and 2 (25%) did not tolerate the device. Conclusion This study demonstrated that oral appliance therapy is efficacious in reducing the AHI by at least 50% or to a value below 10 in a majority of patients. Oral appliance therapy may be a viable alternative to CPAP in selected OSA patients with a history of stroke. Support (if any) No support