A1 Index Research Articles

Transvenous phrenic nerve stimulation for treating central sleep apnea may regulate sleep microstructure

Study objectivesTo assess the impact of transvenous phrenic nerve stimulation (TPNS) on non-rapid eye movement sleep microstructure quantified by cyclic alternating pattern (CAP) in individuals with central sleep apnea (CSA). MethodsWe analyzed baseline and 6-month follow-up overnight polysomnograms (PSG) in 134 CSA patients enrolled in the remedē System Pivotal Trial implanted with TPNS randomized (1:1) to neurostimulation (treatment group) or no stimulation (control group). Differences in CAP rate, A1 index, and A2+A3 index between study arms at follow-up were assessed using Analysis of Covariance adjusted for baseline values. ResultsOn follow-up PSG, the treatment group showed a decrease in the frequency of A2+A3 phases compared to controls (−5.86 ± 11.82 vs. 0.67 ± 15.25, p = 0.006), while the frequency of A1 phases increased more in the treatment group (2.57 ± 11.67 vs. −2.47 ± 10.60, p = 0.011). The change in CAP rate at follow-up was comparable between study arms. ConclusionsTPNS treatment for central sleep apnea may affect sleep microstructure. Brief phases of rapid cortical activity appear to be replaced by short phases of slower cortical activity, which may promote sleep continuity. Further investigations are warranted to elucidate the mechanisms underlying the effect of TPNS on CAP.

Comparing corneal biomechanic changes among solo cataract surgery, microhook ab interno trabeculotomy and iStent implantation

Minimally invasive glaucoma surgery has expanded the surgical treatment options in glaucoma, particularly when combined with cataract surgery. It is clinically relevant to understand the associated postoperative changes in biomechanical properties because they are influential on the measurement of intraocular pressure (IOP) and play an important role in the pathogenesis of open-angle glaucoma (OAG). This retrospective case–control study included OAG patients who underwent cataract surgery combined with microhook ab interno trabeculotomy (µLOT group: 53 eyes of 36 patients) or iStent implantation (iStent group: 59 eyes of 37 patients) and 62 eyes of 42 solo cataract patients without glaucoma as a control group. Changes in ten biomechanical parameters measured with the Ocular Response Analyzer and Corneal Visualization Scheimpflug Technology (Corvis ST) at 3 and 6 months postoperatively relative to baseline were compared among the 3 groups. In all the groups, IOP significantly decreased postoperatively. In the µLOT and control groups, significant changes in Corvis ST-related parameters, including stiffness parameter A1 and stress‒strain index, indicated that the cornea became softer postoperatively. In contrast, these parameters were unchanged in the iStent group. Apart from IOP reduction, the results show variations in corneal biomechanical changes from minimally invasive glaucoma surgery combined with cataract surgery.

Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1

BackgroundSpinal muscular atrophy (SMA) is a severe neuromuscular disorder, the phenotype of the disease is caused by the mutation of the SMN1 (survival motor neuron 1) gene which encodes for the SMN protein. Innovative treatments for SMA have become available and the first molecule approved is Nusinersen, an antisense oligonucleotide that increases the production of SMN protein. Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event‐free survival. For these reasons the aim of the present study is to assess if Nusinersen is able modify sleep architecture and microstructure and to improve sleep structure in these patients. MethodsSixteen patients affected by SMA1 were enrolled in the study (4 boys, 12 girls; median age 72.5 months, intelligence quotient range 24–84). All patients underwent complete nocturnal PSG before the start of the treatment trough intrathecal injections with Nusinersen (T0) and after the fifth infusion (day 180, T180). PSG recordings were visually scored and interpreted according to the indications of the American Academy of Sleep Medicine (AASM) and and microstructure by means of the Cyclic Alternating Pattern (CAP). ResultsAfter 6 months therapy we found a significantly reduced sleep latency and a significantly increased sleep efficiency. Regarding sleep microstructure parameters (CAP), we did not find any significant change after therapy however, it is worth mentioning that a moderate effect size was observed for the increase in CAP A3 index. ConclusionsWe observed short-term effects of Nusinersen on sleep with an improvement in sleep efficiency and reduction in sleep onset latency; regarding sleep microstructure, a moderate effect size was found for the number of CAP A3 subtypes that slightly increased, possibly indicating a slightly higher arousability. This finding points at a probably overall better sleep pattern organization associated with the treatment, but they need to be confirmed by larger studies with patients treated earlier in life and for a longer period.

Restless sleep disorder in children with epileptic and non-epileptic nocturnal attacks.

Restless sleep disorder (RSD) is an important sleep disorder characterised by the presence of frequent large muscle movements (LMM) during sleep, which may be comorbid to other conditions/diseases. In this study, we investigated the frequency and the characteristics of RSD among children who were evaluated by polysomnography (PSG) due to epileptic and non-epileptic nocturnal attacks. We analysed consecutively children younger than 18 years who were referred for PSG recording due to abnormal motor activities during sleep. The diagnosis of nocturnal events as sleep-related epilepsy was made based on the current consensus. Patients who were referred with suspicion of sleep-related epilepsy, but who were diagnosed to have non-epileptic nocturnal events and children with a definitive diagnosis of NREM sleep parasomnias were also enrolled. Sixty-two children were analysed in this study (17 children with sleep-related epilepsy, 20 children with NREM parasomnia, and 25 children with nocturnal events not otherwise classified [neNOS]). The mean number of LMM, LMM index, LMM-associated with arousal and its index were all significantly higher in children with sleep-related epilepsy. Restless sleep disorder was present in 47.1% of patients with epilepsy, 25% of patients with parasomnia, and in 20% of patients with neNOS. The mean A3 duration and the A3 index were higher in children with sleep-related epilepsy and RSD compared with those with parasomnia and restless sleep disorder. Patients with RSD had lower ferritin levels than those without RSD in all subgroups. Our study demonstrates a high prevalence of restless sleep disorder in children with sleep-related epilepsy, associated with an increased cyclic alternating pattern.

Cyclic alternating pattern in non-rapid eye movement sleep in patients with vestibular migraine

ObjectiveThis study aimed to analyze the microstructural features of sleep in patients with vestibular migraine and migraine, and to hypothesize the pathophysiological mechanism between vestibular migraine and sleep disorders. MethodsFrom March 2021 to June 2022, 35 vestibular migraine patients, 35 migraine patients, and 30 controls were collected from the Vertigo Center & Sleep Center of the Second Affiliated Hospital of Zhengzhou University. The anxiety and depression status, sleep quality, and cyclic alternating pattern (CAP) of the three groups were analyzed and compared using the Pittsburgh Sleep Quality Index, Hamilton Anxiety and Depression Scale, and polysomnography (PSG). ResultsThe vestibular migraine group had a higher CAP time (mean 173.64 vs. 122.11, P < 0.001), CAP index (mean 54.25 vs. 37.50, P < 0.001), CAP rate (mean 48.41 vs. 32.31, P < 0.001), CAP sequences (mean 42.60 vs. 29.83, P < 0.001), A3% (mean 45.58 vs. 17.50, P < 0.001) and A2%+A3% (mean 68.87 vs. 38.83, P < 0.001) compared to the control group, with a lower A1 index (mean 16.68 vs. 23.87, P < 0.001) and A1% (mean 31.13% vs. 61.17, P < 0.001). ConclusionPatients with vestibular migraine have poor sleep quality, thalamic-cortical hyperfunction and active arousal system. In addition, high CAP rate and high A2 to A3 ratio make the sleep structure more fragmented.

Effects of CPAP Treatment on Electroencephalographic Activity in Patients with Obstructive Sleep Apnea Syndrome During Deep Sleep with Consideration of Cyclic Alternating Pattern.

To investigate whether continuous positive airway pressure (CPAP) treatment would change EEG activities associated with cyclic alternating pattern (CAP subtype A1, A2, and A3) and non-CAP (NCAP) during non-rapid eye movement sleep stage 3 (N3) in patients with obstructive sleep apnea (OSA). The effects of CPAP treatment on the percentages of sleep stage N3 occupied by the CAP and NCAP, power of EEG waves in the CAP and NCAP were examined in 18 patients with moderate-to-severe OSA undergoing polysomnographic recordings. Apnea and hypopnea index during sleep stage N3 was positively correlated with ratios of phases A2 and A3 duration to total phase A duration [Phase (A2+A3) /Phase A] and negatively correlated with phase A1/phase A. With CPAP treatment, percentages of sleep stage N3 occupied by total CAPs and subtypes A2 and A3, as well as CAP A2 and CAP A3 indexes were significantly decreased while percentages of sleep stage N3 occupied by NCAP (NCAP/N3) and CAP A1 index were significantly increased. In addition, CPAP treatment significantly decreased percentage of respiratory events associated CAPs and increased percentage of non-respiratory related CAPs. Moreover, absolute and relative delta power was significantly increased during phase A1, unchanged during phase A2 and phase B2, and significantly decreased during phases B1, A3 and B3. The absolute power of faster frequency EEG waves in CAPs showed a general trend of decrease. The absolute and relative power of delta waves with amplitudes ≥75 μV, but not <75 μV, was significantly increased. CPAP treatment improves the sleep quality in OSA patients mainly by increasing delta power and decreasing power of higher frequency waves during phase A1, and decreasing CAP A2 and A3 indexes as well as increasing NCAP/N3 and power of delta waves with amplitudes ≥75 μV during NCAP.

Sleep macrostructure and cyclic alternating pattern in patients who underwent surgery for hippocampal sclerosis: A prospective controlled polysomnographic study

IntroductionTemporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) is one of the most common drug-resistant epilepsy. Surgery is currently accepted as an effective and safe therapeutic approach compared to antiseizure medications (ASMs). The study aims to evaluate the effect of surgical treatment of TLE-HS on sleep profile and architecture by subjective and objective evaluation of sleep in basal condition after one month and one year. MethodsThirteen patients with TLE-HS were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) in basal condition (T0), one month (T1) and one year after surgery (T2), respectively. Thirteen healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. ResultsThe comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.003) and REM percentage (p < 0.001). Regarding CAP, patients at T0 showed higher total CAP rate (p < 0.001), CAP rate in N2 (p < 0.001), higher A3 (%) (p =0.001), higher mean duration of A1 (p = 0.002), A3 index (p < 0.001), cycle in sequences (p < 0.001), lower B duration (p < 0.001), cycle mean duration (p < 0.001) than HC. Surgery did not induce significant changes in nocturnal macrostructural polysomnographic variables in T1 and T2. Lower CAP rate (T1 vs T0 and T2 vs T0 p < 0.001), CAP rate in N3 (T1 vs T0 and T2 vs T0 p < 0.001), A3 (%) (T1 vs T0 and T2 vs T0 p < 0.001); lower phase A2 index (T1 vs T0 p < 0.001) and A3 index (T1 vs T0 p < 0.001), lower phase A1 index (T2 vs T0 p < 0.001) and cycle in sequences (T2 vs T0 p = 0.002) higher B mean duration (T2 vs T0 p = 0.002). No significant differences were found between T1 and T2 in CAP parameters. ConclusionWe found a significant NREM sleep instability in patients with TLE-HS compared with HC. In addition, anterior temporal lobectomy (ATL) induced a significant improvement in sleep continuity as evaluated by cyclic alternating pattern already one month later and this effect persisted after one year. ALT seems to restore a more resilient sleeping brain.

Sleep microstructure in attention deficit hyperactivity disorder according to the underlying sleep phenotypes.

The analysis of sleep microstructure in attention deficit hyperactivity disorder (ADHD) revealed an under-representation of the EEG slow component during NREM sleep. Previous studies either excluded or did not characterize objectively sleep disorders, which notoriously affect sleep architecture. The present study aimed to investigate the cyclic alternating pattern in a real clinical sample of children with ADHD, in whom sleep disorders could be considered. Twenty-seven consecutively enrolled drug-naïve children (mean age, 10.53 years; nine females) and 23 controls (mean age, 10.22years; 11 females) underwent a full sleep investigation, including attended video-polysomnography. Visual cyclic alternating pattern analysis was performed in a blinded way. Children with ADHD had one or more sleep disorders (a narcolepsy-like phenotype was found in two cases, sleep onset insomnia in three cases, arousal disorder in one case, movement disorder phenotype in six cases and obstructive sleep apnea in 11 cases, and six children had sleep-related epileptiform discharges). Children with ADHD and normal controls showed a similar microstructure with a cyclic alternating pattern rate of about 50%. Children with obstructive sleep apnea had a significantly higher cyclic alternating pattern rate during stage N3. Despite not reaching statistical differences, a lower cyclic alternating pattern rate and A1 index were found in children without epileptic abnormalities/obstructive sleep apnea. Our analysis might allow differentiation of the "primary form" of ADHD associated with a decrease of NREM instability from those forms associated with sleep apnea and epileptic activity.

Efficacy and safety of a single intra-articular injection of 6\u2009ml Hylan G-F 20 compared to placebo in Chinese\xa0patients with symptomatic knee osteoarthritis

BackgroundSingle 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity.MethodsThis was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection.ResultsFour hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/− 40.5% and − 2.271 (0.110) /− 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%).ConclusionsWhile the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients.Trial registrationProspectively registered Jun 16, 2017 at www.clinicaltrials.gov (NCT03190369).

Identifying Top Predictors of Change in Noncalcified Coronary Burden in Psoriasis by Machine Learning Over 1-Year

Background: Psoriasis is associated with accelerated non-calcified coronary burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that improved NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that worsened NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.

Sleep EEG microstructure in children and adolescents with attention deficit hyperactivity disorder: a systematic review and meta-analysis.

Attention deficit hyperactivity disorder (ADHD) is commonly associated with sleep problems, possibly due to shared pathophysiology. Microstructural sleep electroencephalographic (EEG) alterations may likely represent markers of disordered cortical maturation in ADHD, although literature data are still conflicting, deserving further assessment. After having systematically reviewed the literature, we included 11 studies from 598 abstracts, and assessed 23 parameters of cyclic alternating pattern (CAP), four parameters of sleep EEG power and one parameter of sleep graphoelements through 29 meta-analyses and, when possible, univariate meta-regressions. Slow wave activity (SWA) in ADHD was significantly higher in early childhood and lower in late childhood/adolescence compared to controls, with an inversion point at 10 years. Total CAP rate and CAP A1 index in non-rapid eye movement (NREM) stage 2 sleep, and CAP A1 rate in NREM sleep were significantly lower in ADHD patients than controls. SWA and CAP A1 changes are therefore possible markers of altered cortical maturation in ADHD, consistently with the neuropsychological deficits characterizing the disorder, likely fostering earlier detection of at-risk/milder conditions, and more tailored therapeutic interventions.

Effects of eslicarbazepine as add-on therapy on sleep architecture in temporal lobe epilepsy: results from “Esleep” study

RationaleStudies looking at the effect of antiseizure medications (ASMs) on the sleep microstructure of subjects with epilepsy are scarce. This study aims to evaluate the impact of eslicarbazepine (ESL) as add-on therapy on the sleep microstructure in temporal lobe epilepsy (TLE). MethodsTwelve patients affected by TLE were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Ten healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. ResultsTen patients completed the study. The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.049), REM percentage (p = 0.002), higher REM latency (p = 0.02), N2 (p = 0.001) and WASO (p = 0.01). Regarding CAP, patients at T0 showed higher CAP rate in N1 (p = 0.01), lower A1 (%) (p = 0.03), higher A3 (%) (p = 0.01), higher mean duration of A (p = 0.02) and A3 (p = 0.006), A3 index (p = 0.02) than HC. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Furthermore, the ESS score showed no modification after treatment. Lower CAP rate in N3 (p = 0.02), phase A2 index (p = 0.02) average number of CAP cycle per sequences and mean duration of CAP sequences (both p = 0.02) was evident after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p = 0.09) and N2 (p = 0.09), and for the increase of B phase mean duration (p = 0.07). ConclusionWe found significant improvement in sleep continuity as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep fragmentation in patients with TLE, and hence enhance sleep quality. Our results suggest a favourable sleep profile with the use of ESL.

0818 Cyclic Alternating Pattern as Indicator for Subjective Sleep Quality in Community-Dwelling Older Men

Abstract Introduction The micro-architecture of NREM sleep displays a cyclic alternating pattern (CAP) comprising activation phases of slow high-amplitude waves (A1), fast low-amplitude brain activity rhythms (A3) or a mixture of both (A2). In this study, we investigated the relationship between CAP and subjective sleep quality parameters reported by community-dwelling older men from the Osteoporotic Fractures in Men Sleep Study. Methods CAP was scored in 2,811 overnight EEG recordings using a high performance automated CAP detection system. We quantified the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). Also, participants were asked to score the quality of their sleep on a Likert scale with five items from light to deep, from short to long, and from restless to restful. The relationship between CAP parameters and the subjective sleep quality measures was determined using ANCOVA with traditional sleep disturbance indices such as obstructive apnea-hypopnea index and arousal index as covariate. Results CAP rate decreased significantly with increasing quality of sleep for all three subjective measures (light vs. deep: 58.8±22.3% vs. 54.6±20.5%, p &amp;lt; 0.001; short vs. long: 58.4±21.4% vs. 55.1±20.5%, p &amp;lt; 0.001, restless vs. restful: 59.4±20.8% vs. 55.6±21.0%, p = 0.002). The A1 index did not show any significant variations across all three sleep quality parameters. The A2+A3 index behaved similarly to the CAP rate with decreasing values for each subjective measure (all: p &amp;lt; 0.001). Conclusion CAP rate, especially A2+A3-phases, are reduced in older men who report good sleep quality, while A1 index did not show any significant relationship with subjective sleep quality measures. Hence, CAP is an indicator of sleep quality. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

0392 The Effect of Benzodiazepine Use on Non-REM Sleep Instability in Community-Dwelling Older Men

Abstract Introduction Previous studies on the implications of benzodiazepine (BZD), a widely prescribed pharmacotherapeutic treatment method for sleep insomnia, on sleep architecture demonstrated significantly reduced EEG activity in low-frequency bands. In this study, we explore the effect of BZD on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 30 older men on long-acting BZD (LBZD), 35 older men on short-acting BZD (SBZD), and 50 age-matched men who did not use BZD (NBZD), participating in the Osteoporotic Fractures in Men Sleep Study (MrOS sleep). A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The relationship between CAP parameters and BZD use was determined using the Kruskal-Wallis test by ranks with Bonferroni correction for post-hoc analysis. Results CAP rate was significantly decreased in older men using long-acting BZD (NBZD: 59.6±18.0%, LBZD: 46.9±13.1%, SBZD: 53.0±20.1%) as compared to non-BZD user (p &amp;lt; 0.01). All BZD users demonstrated significantly lower frequencies of A1-phases (NBZD: 19.9±23.0 no./h, LBZD: 6.9±13.3 no./h, SBZD: 4.5±9.9 no./h) as compared to non-BZD users (LBZD: p &amp;lt; 0.01, SBZD: p &amp;lt; 0.001). The A2+A3 index did not show any variations between the three groups. Conclusion Older men using long-acting BZD demonstrate a significantly reduced CAP rate during sleep, particularly less frequent A1-phases, compared to the control group. Moreover, short-acting BZD user show significantly less frequent A1-phases but no difference in CAP rate and A2+A3-phases than older men using no BZD. Hence, BZD usage has a major adverse effect on the occurrence of EEG slow waves. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

0393 The Effect of Trazadone Use on Non-REM Sleep Instability in Community-Dwelling Older Men

Abstract Introduction With steadily growing numbers of patients with a depressive disorder, the effect of antidepressants on sleep architecture is of increasing concern. One major oral antidepressant medication is trazadone, which has also been prescribed in low doses for sleep insomnia treatment. Here, we investigate the effect of trazadone on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 41 older men on trazadone (TRZ) and 50 age-matched men who did not use trazadone (NTRZ), participating in the Osteoporotic Fractures in Men Sleep Study. A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The effect of TRZ on CAP parameters was determined using the Mann-Whitney U test. Results CAP rate was significantly decreased in men using trazadone (NTRZ: 58.2±19.7%, TRZ: 47.9±15.9%) as compared to non-trazadone user (p &amp;lt; 0.01). Subtype indices did not show any significant difference between both groups but to some extent less frequent A2-A3 phases for TRZ user (A1-phases: NTRZ 13.0±18.7 no./h vs. TRZ 10.8±20.4 no./h, p = 0.35; A2+A3-phases: NTRZ 51.5±33.7 no./h vs. TRZ 44.7±23.3 no./h, p = 0.068). Conclusion CAP rate was significantly decreased in older men on trazadone as compared to older men who did not use trazadone, suggesting that trazadone usage has a stabilising effect on sleep micro-structure. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

Characterization of cyclic alternating pattern during sleep in older men and women using large population studies.

To assess the microstructural architecture of non-rapid eye movement (NREM) sleep known as cyclic alternating pattern (CAP) in relation to the age, gender, self-reported sleep quality, and the degree of sleep disruption in large community-based cohort studies of older people. We applied a high-performance automated CAP detection system to characterize CAP in 2,811 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 426 women from the Study of Osteoporotic Fractures (SOF). CAP was assessed with respect to age and gender and correlated to obstructive apnea-hypopnea index, arousal index (AI-NREM), and periodic limb movements in sleep index. Further, we evaluated CAP across levels of self-reported sleep quality measures using analysis of covariance. Age was significantly associated with the number of CAP sequences during NREM sleep (MrOS: p = 0.013, SOF = 0.051). CAP correlated significantly with AI-NREM (MrOS: ρ = 0.30, SOF: ρ = 0.29). CAP rate, especially the A2+A3 index, was inversely related to self-reported quality of sleep, independent of age and sleep disturbance measures. Women experienced significantly fewer A1-phases compared to men, in particular, in slow-wave sleep (N3). We demonstrate that automated CAP analysis of large-scale databases can lead to new findings on CAP and its subcomponents. We show that sleep disturbance indices are associated with the CAP rate. Further, the CAP rate is significantly linked to subjectively reported sleep quality, independent from traditionally scored markers of sleep fragmentation. Finally, men and women show differences in the microarchitecture of sleep as identified by CAP, despite similar macro-architecture.

Implementation of a Personalized Care Plan for Patients With Type 2 Diabetes Is Associated With Improvements in Clinical Outcomes: An Observational Real-World Study.

Objective: To analyze the clinical outcomes of patients with type 2 diabetes (T2D) before and after implementation of a personalized care plan in the primary health care setting. Design: Observational, retrospective, real-world study. Setting: All T2D patients with a care plan in Rovaniemi Health Center, Rovaniemi, Finland, for whom data were available from a baseline visit (in 2013-2015 during which the care plan was written) and from a follow-up visit, including an updated care plan by the year 2017. Subjects: In total, 447 patients were included. Mean age was 66.9 (SD 10.1) years, 58.8% were male, 15.4% were smokers, 33.1% had vascular disease, and 17.0% were receiving insulin treatment. The mean follow-up time was 14.4 months. Main Outcome Measures: Glycosylated hemoglobin A1 (HbA1c), low-density lipoprotein (LDL), blood pressure (BP), and body mass index (BMI). Clinical values were taken at both baseline and follow-up. Results: LDL decreased by 0.2 mmol/L, systolic blood pressure by 2.2 mm Hg, diastolic blood pressure by 1.5 mm Hg, and BMI by 0.5 kg/m2 (P < .05 for each). The decrease in HbA1c was 0.8 mmol/mol (P = .07). Conclusion: We observed statistically significant decreases in LDL, BP, and BMI. Our results indicate that, over 14 months of follow-up, implementation of a written care plan was associated with small improvements in the clinical outcomes of T2D patients in a primary health care study population in a real-world setting.

NREM Sleep Instability in Pediatric Migraine Without Aura.

Children with migraine headaches appear to have a range of sleep disturbances. The aim of the present study was to assess the NREM sleep instability in a population of school-aged individuals affected by migraine without aura (MoA). Thirty-three children with MoA (20 males, 13 females, mean age 10.45 ± 2.06 years) underwent to overnight Polysomnographic (PSG) recordings and Cyclic Alternating Pattern (CAP) analyses accordingly with international criteria. MoA group showed a reduction in sleep duration parameters (TIB, SPT, TST; p ≤ 0.001 for all) and in arousal index during REM sleep and an increase in awakenings per hour (AWK/h) vs. Controls (C) (p = 0.008). In particular, MoA children showed a reduced CAP rate% (p ≤ 0.001), CAP rate% in S1 (p ≤ 0.001) and CAP rate% in SWS (p = 0.004) vs. C. Moreover, A phases distribution were characterized by a reduction in slow wave components (total number CAP A1%, CAP A1 index) (p ≤ 0.001) and an increase of fast components representation (total number of CAP A2% and CAP A3%) (p < 0.001) in MoA vs. C. Moreover, MoA children showed an increased A1 and A2 mean duration (p ≤ 0.001). Our findings show a reduction of arousability in MoA group and lower NREM lower sleep instability associated with MoA in children.

Decision Support System on Selection of Lecturer Research Grant Proposals using Preferences Selection Index

The Institute for Research and Community Service is a forum for lecturers at every university/institution to develop their knowledge according to their respective disciplines through research fields. This study aims to determine the recipient of the best research grant at STIKOM Tunas Bangsa Pematangsiantar. Research data comes from relevant agencies. There are 9 names of lecturers that are used as alternatives and 5 criteria as the assessment of grantees, namely type of problem formulation (C1), research output opportunities (C2), research method (C3), literature review (C4) and research feasibility (C5). This study uses the Preference selection index (PSI) method. In this method does not require relative determination of attributes, so the researcher does not need to determine the weight criteria. Based on the results of the study obtained several alternatives with the highest preference value, A8 (index selection value 0.8819), A9 (index selection value 0.8627), A4 (index selection value 0.8447), A3 (index selection value 0.83123) and A5 (Index selection value 0.8184) are entitled to get an internal research grant at STIKOM Tunas Bangsa. With this system, it can be used as a comparison between reviewer evaluators and the PSI system so as to maintain the quality of assessment in determining the recipients of internal research grants objectively. It is hoped that this research can provide recommendations to the Institute for Research and Community Services in determining internal lecturer research proposal grants so that the results obtained are more objective.

Isolated rapid eye movement sleep behavior disorder and cyclic alternating pattern: is sleep microstructure a predictive parameter of neurodegeneration?

To evaluate the role of sleep cyclic alternating pattern (CAP) in patients with isolated REM sleep behavior disorder (IRBD) and ascertain whether CAP metrics might represent a marker of phenoconversion to a defined neurodegenerative condition. Sixty-seven IRBD patients were included and classified into patients who phenoconverted to a neurodegenerative disease (RBD converters: converter REM sleep behavior disorder [cRBD]; n = 34) and remained disease-free (RBD non-converters: non-converter REM sleep behavior disorder [ncRBD]; n = 33) having a similar follow-up duration. Fourteen age- and gender-balanced healthy controls were included for comparisons. Compared to controls, CAP rate and CAP index were significantly decreased in IRBD mainly due to a decrease of A1 phase subtypes (A1 index) despite an increase in duration of both CAP A and B phases. The cRBD group had significantly lower values of CAP rate and CAP index when compared with the ncRBD group and controls. A1 index was significantly reduced in both ncRBD and cRBD groups compared to controls. When compared to the ncRBD group, A3 index was significantly decreased in the cRBD group. The Kaplan-Meier curve applied to cRBD estimated that a value of CAP rate below 32.9% was related to an average risk of conversion of 9.2 years after baseline polysomnography. IRBD is not exclusively a rapid eye movement (REM) sleep parasomnia, as non-rapid eye movement (non-REM) sleep microstructure can also be affected by CAP changes. Further studies are necessary to confirm that a reduction of specific CAP metrics is a marker of neurodegeneration in IRBD.