Objective: This is one of two separate clinical trials to evaluate the efficacy and safety of modafinil, a novel wake-promoting agent, in patients with excessive daytime sleepiness (EDS) associated with narcolepsy. Methods: In this 9-week, randomized, placebo-controlled, double-blind, 21-center clinical trial, patients were randomized to receive fixed daily doses of modafinil 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 2-week treatment discontinuation phase was included to evaluate the effects of withdrawal on patients who had been receiving modafinil. A total of 271 patients who were naive to modafinil received study medication in the 9-week trial and 240 patients received study medication in the discontinuation phase. Results: Treatment with modafinil resulted in significant improvement in two objective measures of EDS: the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Additionally, patient self-assessment of sleepiness was significantly improved, as measured by the Epworth Sleepiness Scale, and level of illness was significantly reduced on the independent clinician assessment, the Clinical Global Impression of Change. Nighttime sleep, monitored by nocturnal polysomnography, was not adversely effected with modafinil treatment compared with placebo treatment. The most frequent adverse experience was headache, which was not significantly greater for modafinil than placebo. During treatment discontinuation, individuals who had been receiving modafinil experienced a return of their EDS to baseline levels. During treatment discontinuation, patients did not experience symptoms associated with amphetamine withdrawal syndrome. For up to 9 weeks of daily use there was no evidence for the development of dependence at the dose levels studied. Conclusion: The data indicate that modafinil has an excellent safety profile and is very well tolerated. Modafinil is an effective treatment for excessive daytime sleepiness in narcolepsy and shows continued efficacy with up to 9 weeks of daily use.

Narcolepsy is considered a homogeneous clinical entity when excessive daytime sleepiness and cataplexy are present. Cataplexy is a polymerphic symptom that can be very mild and is thus subjectively defined. The Multiple Sleep Latency Test (MSLT) is widely used as a diagnostic test for narcolepsy. A short mean sleep latency and multiple sleep onset REM periods (SOREMPs) are typically observed in narcoleptic patients. The discovery of a tight association of narcolepsy with HLA class II antigens offers a unique opportunity to explore the respective value of the MSLT or of the presence of clear-cut cataplexy in defining an etiologically homogeneous group of narcoleptic patients. In this study, we carried out HLA typing for DR15(DR2) and DQB1*0602 in 188 narcoleptic patients with cataplexy in three ethnic groups (24 Asians, 61 Blacks, and 163 Caucasians). These results confirm the importance of DQB1*0602 typing rather than DR15 (DR2) typing in Black narcoleptic patients and demonstrate that the presence of clear-cut cataplexy is a better predictor for DQB1*0602 positivity than the presence of abnormal MSLT results.

Background: Sleep problems are common in lung cancer survivors, yet little is known about the prevalence, determinants, and effects on quality of life (QoL) of these sleep problems in long-term lung cancer survivors. Methods: A case-control study design comparing 76 elderly lung cancer survivors (LCS, >5 years post diagnosis with mean survival time of 8 years ± 2.1 years) and 78 elderly non-cancer controls (NCC). Measurements included a standardized questionnaire for sleep (Pittsburgh Sleep Quality Index-PSQI), and analogue scales for dyspnea, pain, and other comorbid symptoms, as well as demographic factors and cancer history. Results: Overall, 56.6% of LCS had poor sleep (PSQI global score > 5) as compared to only 29.5% of NCC (p < 0.001), and 49.2% of LCS who did not have sleep difficulties prior to their lung cancer diagnosis ultimately developed them. There was also evidence of significant impairments in sleep efficiency in LCS (78.3%) relative to NCC (89.6%, p < 0.001), predominantly due to increased nocturnal awakenings. A single-item analogue scale for sleep quality was not as effective in identifying sleep problems as more specific questions about sleep duration and sleep efficiency. Poor sleep quality was significantly correlated with impairments in quality of life, even when controlling for other factors, such as dyspnea. Conclusions: Even 8 years after diagnosis, LCS continue to have significant sleep difficulties. By asking specific questions about sleep medication use, nocturnal awakenings and sleep efficiency, health care providers can identify sleep problems that could be treated and potentially improve the quality of life of their patients. © 2007 Elsevier Ireland Ltd. All rights reserved.

Introduction: Sleepiness in obstructive sleep apnoea is associated with cardiovascular risk; however, the biological mechanisms are not known. This study explored whether those with subjective sleepiness have increased plasma tumour necrosis factor-related protein 1 (C1qTNF1), a novel adipose-derived hormone (adipokine), and 24-h ambulatory blood pressure (ABP) compared to those without sleepiness in newly diagnosed, treatment-naïve participants with obstructive sleep apnoea. Methods: Overall, 94 participants were included in the analysis. Participants completed the Epworth Sleepiness Scale (ESS), 24-h ABP was monitored, and plasma C1qTNF1 was measured. Sleepy participants were defined as ESS≥10 and nonsleepy as ESS<10. Multiple linear regression was used to explore differences in C1qTNF1, and 24-h mean arterial pressure (MAP) between sleepy and nonsleepy participants, adjusting for age, sex, body mass index, apnoea-hypopnoea index, and smoking status. Results: C1qTNF1 was significantly higher in sleepy participants (n=57) compared to nonsleepy participants (n=37) (β=0.41 NPX, 95% CI 0.02, 0.80; p=0.04). The 24-h MAP was significantly higher in sleepy participants compared to nonsleepy participants (β=4.06 mmHg, 95% CI 0.36, 7.77; p=0.03). Conclusions: Our findings show that sleepiness is associated with inflammation and higher 24-h MAP in sleep apnoea.

The objective of the study was to determine if sleep disorder, depression or anxiety screening status was associated with safety outcomes in a diverse population of hospital workers. A sample of shift workers at four hospitals participated in a prospective cohort study. Participants were screened for five sleep disorders, depression and anxiety at baseline, then completed prospective monthly surveys for the next 6 months to capture motor vehicle crashes, near-miss crashes, occupational exposures and medical errors. We tested the associations between sleep disorders, depression and anxiety and adverse safety outcomes using incidence rate ratios adjusted for potentially confounding factors in a multivariable negative binomial regression model. Of the 416 hospital workers who participated, two in five (40.9%) screened positive for a sleep disorder and 21.6% screened positive for depression or anxiety. After multivariable adjustment, screening positive for a sleep disorder was associated with 83% increased incidence of adverse safety outcomes. Screening positive for depression or anxiety increased the risk by 63%. Sleep disorders and mood disorders were independently associated with adverse outcomes and contributed additively to risk. Our findings suggest that screening for sleep disorders and mental health screening can help identify individuals who are vulnerable to adverse safety outcomes. Future research should evaluate sleep and mental health screening, evaluation and treatment programmes that may improve safety.

Background: Insomnia is a prevalent sleep disorder, and it has been increasingly associated with cardiovascular morbidity and mortality. The reasons for this relationship are not completely understood but may involve endothelial dysfunction. In this study, we hypothesized that insomnia symptoms would be associated with reduced endothelial function. Methods: Working adults (n = 496, 67.5% female, 78.6% white, mean age 48.7 [SD, 10.8] years, body mass index 28.2 [SD, 6.7] kg/m 2 , diabetes 5.8%, hypertension 20.0%, hyperlipidemia 17.9%, heart disease 2.6%) enrolled in the Emory-Georgia Tech Predictive Health Institute study completed baseline demographic, clinical, depression (Beck Depression Inventory II), anxiety (General Anxiety Disorder 7), sleep (Pittsburg Sleep Quality Index), and noninvasive endothelial function (brachial artery flow-mediated dilation [FMD]) measures. Insomnia symptoms were defined as subjective sleep latency of 30 minutes or longer, nighttime or early morning awakenings, and/or sleep medication use occurring 3 times or more per week in the past month. Results: Insomnia symptoms were reported by 39.5% of participants. Multivariable regression models showed that insomnia symptoms, age, baseline artery diameter, and dyslipidemia were inversely related to FMD. After adjusting for age, baseline artery diameter, and dyslipidemia, participants reporting insomnia symptoms had lower FMD than did participants reporting better sleep (adjusted FMD mean, 6.13% [SD, 0.28%] vs 6.83% [SD, 0.26%], P =.035). Conclusion: In this study, insomnia symptoms were associated with reduced FMD. Research examining the therapeutic benefits of treating insomnia on endothelial function and future cardiovascular risk is warranted.

Sleep is essential for optimal health, well-being, and cognitive functioning, and yet nationwide, youth are not obtaining consistent, adequate, or high-quality sleep. In fact, more than two-thirds of US adolescents are sleeping less than 8 hours nightly on school nights. Racial and ethnic minority children and adolescents are at an increased risk of having shorter sleep duration and poorer sleep quality than their white peers. In this review, we critically examined and compared results from 23 studies that have investigated racial/ethnic sleep disparities in American school-aged children and adolescents ages 6-19 years. We found that White youth generally had more sufficient sleep than minority youth, Hispanics had more than Blacks, and there was inconclusive evidence for Asians and other minorities. Recommendations for researchers include the following: (1) explore underlying causes of the disparities of these subpopulations, with a particular interest in identifying modifiable causes; (2) examine factors that may be impacted by racial/ethnic sleep disparities; (3) use a multidimensional approach to measuring sleep disparities; and (4) examine how beliefs about sleep are patterned by race/ethnicity. Understanding sleep disparities can inform interventions, policies, and educational programs to minimize sleep disparities and their impact on health, psychological, and educational outcomes.