Correlates of sleep quality and excessive daytime sleepiness in people with opioid use disorder receiving methadone treatment
- 作者列表："Baldassarri, Stephen R.","Beitel, Mark","Zinchuk, Andrey","Redeker, Nancy S.","Oberleitner, David E.","Oberleitner, Lindsay M. S.","Carrasco, Danilo","Madden, Lynn M.","Lipkind, Nathan","Fiellin, David A.","Bastian, Lori A.","Chen, Kevin","Yaggi, H. Klar","Barry, Declan T.
Purpose The aim of this study was to evaluate the prevalence and clinical correlates of impaired sleep quality and excessive daytime sleepiness among patients receiving methadone for opioid use disorder (OUD). Methods Patients receiving methadone ( n = 164) completed surveys assessing sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), and related comorbidities. We used bivariate and multivariable linear regression models to evaluate correlates of sleep quality and daytime sleepiness. Results Ninety percent of patients had poor sleep quality (PSQI >5), and the mean PSQI was high (11.0 ±4). Forty-six percent reported excessive daytime sleepiness (ESS > 10). In multivariable analyses, higher PSQI (worse sleep quality) was significantly associated with pain interference (coefficient = 0.40; 95% CI = 0.18–0.62; β = 0.31), somatization (coefficient = 2.2; 95% CI = 0.75–3.6; β = 0.26), and negatively associated with employment (coefficient = − 2.6; 95% CI = − 4.9 to − 0.19; β = − 0.17). Greater sleepiness was significantly associated with body mass index (coefficient = 0.32; 95% CI = 0.18–0.46; β = 0.33), and there was a non-significant association between sleepiness and current chronic pain (coefficient = 1.6; 95% CI = 0.26–3.5; β = 0.13; p value = 0.09). Conclusions Poor sleep quality and excessive daytime sleepiness are common in patients receiving methadone for OUD. Chronic pain, somatization, employment status, and obesity are potentially modifiable risk factors for sleep problems for individuals maintained on methadone. People with OUD receiving methadone should be routinely and promptly evaluated and treated for sleep disorders.
目的本研究的目的是评估接受美沙酮治疗阿片类药物使用障碍 (OUD) 患者中睡眠质量受损和白天过度嗜睡的患病率和临床相关因素。方法美沙酮患者 (n = 164) 完成了评估睡眠质量 (匹兹堡睡眠质量指数 [PSQI]) 、日间嗜睡 (Epworth 嗜睡量表 [ESS]) 和相关合并症的调查。我们使用双变量和多变量线性回归模型来评估睡眠质量和日间嗜睡的相关性。结果 11.0 的患者睡眠质量差 (PSQI >5)，平均 PSQI 高 (± 4)。6% 报告白天过度嗜睡 (ESS> 10)。在多变量分析中，较高的 PSQI (较差的睡眠质量) 与疼痛干扰显著相关 (系数 = 0.40; 95% ci = 0.18-0.62; Β = 0.31),躯体化 (系数 = 2.2; 95% ci = 0.75-3.6; Β = 0.26)，与就业负相关 (系数 = − 2.6; 95% ci =-4.9 至-0.19; Β =-0.17)。嗜睡程度与体重指数显著相关 (系数 = 0.32; 95% ci = 0.18-0.46; Β = 0.33),嗜睡与当前慢性疼痛之间无显著相关性 (系数 = 1.6; 95% ci = 0.26-3.5; Β = 0.13; P值 = 0.09)。结论在接受美沙酮治疗的患者中，睡眠质量差和白天过度嗜睡是常见的。慢性疼痛、躯体化、就业状况和肥胖是维持服用美沙酮的个体睡眠问题的潜在可改变的危险因素。接受美沙酮治疗的 OUD 患者应常规及时评估和治疗睡眠障碍。
METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.
METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.
METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.