Light Exposure Among Adolescents With Delayed Sleep Phase Disorder: A Prospective Cohort Study

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n?=?16, 15.3?±?1.8 yrs) and unaffected controls (n?=?22, 13.7?±?2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00?h and 05:00 to 14:00?h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p?<?.02, 22:00–02:00?h) and less morning (p?<?.05, 08:00–09:00?h and 10:00–12:00?h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p?<?.03, 5–7?h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p?<?.001 and p?=?.02, respectively) and morning (p?=?.01 and p?<?.001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p?<?.001). Increased total sleep time also correlated with increased exposure during the 9?h before sleep onset (p?=?.01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p?<?.001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. (Author correspondence: auger.raymond1@mayo.edu)     

Wearing blue light-blocking glasses in the evening advances circadian rhythms in the patients with delayed sleep phase disorder: An open-label trial

It has been recently discovered that blue wavelengths form the portion of the visible electromagnetic spectrum that most potently regulates circadian rhythm. We investigated the effect of blue light-blocking glasses in subjects with delayed sleep phase disorder (DSPD). This open-label trial was conducted over 4 consecutive weeks. The DSPD patients were instructed to wear blue light-blocking amber glasses from 21:00 p.m. to bedtime, every evening for 2 weeks. To ascertain the outcome of this intervention, we measured dim light melatonin onset (DLMO) and actigraphic sleep data at baseline and after the treatment. Nine consecutive DSPD patients participated in this study. Most subjects could complete the treatment with the exception of one patient who hoped for changing to drug therapy before the treatment was completed. The patients who used amber lens showed an advance of 78 min in DLMO value, although the change was not statistically significant (p = 0.145). Nevertheless, the sleep onset time measured by actigraph was advanced by 132 min after the treatment (p = 0.034). These data suggest that wearing amber lenses may be an effective and safe intervention for the patients with DSPD. These findings also warrant replication in a larger patient cohort with controlled observations.     

Circadian rhythmicity of cortisol and body temperature: morningness-eveningness effects

The purpose of this study was to describe and compare the circadian rhythm of body temperature and cortisol, as well as self-reported clock times of sleep onset and offset on weekdays and weekends in 19 healthy adult "larks" (morning chronotypes) and "owls" (evening chronotypes), defined by the Home and Ostberg questionnaire. Day-active subjects entered the General Clinical Research Center, where blood was sampled every 2 h over 38 h for later analysis for cortisol concentration by enzyme immunoassay. Rectal body temperature was measured continuously. Lights were turned off at 22:30 for sleep and turned on at 06:00, when subjects were awakened. The acrophases (peak times) of the cortisol and temperature rhythms occurred 55 minutes (P < or = .05) and 68 minutes (P < .01), respectively, earlier in the morningness group. The amplitude of the cortisol rhythm was lower in the eveningness than in the morningness group (P = n.s.). Subject groups differed on all indices of habitual and preferred timing of sleep and work weekdays and weekends (P = .05-.001).     

Short and long-term effects of unguided internet-based cognitive behavioral therapy for chronic insomnia in morning and evening persons: a post-hoc analysis

ABSTRACT

A post-hoc analysis comparing morning and evening persons with insomnia on sleep and mental health characteristics was conducted in order to investigate whether an Internet-based cognitive behavioral therapy for insomnia (ICBTi) was effective both for morning and evening persons. Adult patients (N = 178, mean age = 44.8, 67% females) with insomnia were randomized to either ICBTi (N = 92; morning persons = 41; evening persons = 51) or a web-based patient education condition (N = 86; morning persons = 44; evening persons = 42). All patients were assessed with sleep diaries, the Insomnia Severity Index (ISI), the Bergen Insomnia Scale (BIS), the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Hospital Anxiety and Depression Scale (HADS) and the Chalder Fatigue Scale (CFQ). Patients were characterized as morning or evening persons based on a median split on the Horne-Östberg Morningness Eveningness Questionnaire. Short and long-term effects of treatment were examined with mixed-model repeated-measures analyses. Morning and evening persons did not differ in terms of age, gender or educational status. At baseline, morning persons had more wake time after sleep onset (d= 0.54, p < .001) and more early morning awakening (d= 0.38, p < .05) compared to evening persons, while evening persons reported longer sleep onset latency (d= 0.60, p < .001), more time in bed (d= 0.56, p < .001), longer total sleep time (d= 0.45, p < .01), more fatigue (d= 0.31, p < .05) and more dysfunctional beliefs and attitudes about sleep (d= 0.47, p < .01). Despite these differences at baseline, both morning and evening persons receiving ICBTi benefitted more across most measures compared to morning and evening persons who received patient education. For morning persons in the ICBTi group, ISI scores were reduced from 17.3 at baseline to 8.8 (d_pre-post = 2.48, p < .001) at post-assessment, and to 10.0 at 18-month follow up (d_pre-post18m = 2.13, p < .001). Comparable results were found for evening persons in the ICBTi group, with a reduction in ISI scores from 17.4 at baseline to 8.6 (d_pre-post = 2.24, p < .001) at post-assessment, and to 8.7 at 18-month follow up (d_pre-post18m = 2.19, p < .001). Similar results were found on the BIS, DBAS, HADS, CFQ and sleep diary data. Despite different insomnia symptomatology between the two groups, the current study suggests that ICBTi is effective across scores on the morningness-eveningness dimension. The study was pre-registered at: ClinicalTrials.gov Identifier: NCT02261272.     

The impact of sleep timing and bright light exposure on attentional impairment during night work

The prevalence of hazardous incidents induced by attentional impairment during night work and ensuing commute times is attributable to circadian misalignment and increased sleep pressure. In a 10-day shift work simulation protocol (4 day shifts and 3 night shifts), the efficacies of 2 countermeasures against nighttime (2300 to 0700 h) attentional impairment were compared: (1) Morning Sleep (0800 to 1600 h; n = 18) in conjunction with a phase-delaying light exposure (2300 to 0300 h), and (2) Evening Sleep (1400 to 2200 h; n = 17) in conjunction with a phase-advancing light exposure (0300 to 0700 h). Analysis of the dim light salivary melatonin onset indicated a modest but significant circadian realignment in both sleep groups (evening sleep: 2.27 +/- 0.6 h phase advance, p < 0.01; morning sleep: 4.98 +/- 0.43 h phase delay, p < 0.01). Daytime sleep efficiency and total sleep time did not differ between them or from their respective baseline sleep (2200 to 0600 h; p > 0.05). However, on the final night shift, the evening sleep subjects had 37% fewer episodes of attentional impairment (long response times: 22 +/- 4 vs. 35 +/- 4; p = 0.02) and quicker responses (p < 0.01) on the Psychomotor Vigilance Task than their morning sleep counterparts. Their response speed recovered to near daytime levels (p = 0.47), whereas those of the morning sleep subjects continued to be slower than their daytime levels (p = 0.008). It is concluded that partial circadian realignment to night work in combination with reduced homeostatic pressure contributed to the greater efficacy of a schedule of Evening Sleep with a phase-advancing light exposure as a countermeasure against attentional impairment, over a schedule of Morning Sleep with a phase-delaying light exposure. These results have important implications for managing patients with shift work disorder.     

Effect of Evening Exposure to Dim or Bright Light on the Digestion of Carbohydrate in the Supper Meal

In a previous study we found that daytime exposure to bright as compared to dim light exerted a beneficial effect on the digestion of the evening meal. This finding prompted us to examine whether the digestion of the evening meal is also affected by evening light intensity. Subjects lived in light of 200 lux during the daytime (08:00–17:00 h) and took their evening meal at 17:00 h under 20 lux (evening dim‐light condition: 17:00–02:00 h) or 2000 lux (evening bright‐light condition: 17:00–02:00 h) until retiring at 02:00 h. Assessment of carbohydrate digestion of the evening meal was accomplished by a breath hydrogen test that is indicative of the malabsorption of dietary carbohydrate. Hydrogen excretion in the breath in the evening under the dim‐light condition was significantly less than under the bright‐light condition (p < 0.05). This finding is the opposite to that obtained in previous experiments in which subjects were exposed to the different intensities of light during the daytime, and indicates that the exposure to dim light in the evening exerts a better effect on carbohydrate digestion in the evening meal than does the exposure to bright light.     

Differences in circadian phase and weekday/weekend sleep patterns in a sample of middle-aged morning types and evening types

Factors contributing to sleep timing and sleep restriction in daily life include chronotype and less flexibility in times available for sleep on scheduled days versus free days. There is some evidence that these two factors interact, with morning types and evening types reporting similar sleep need, but evening types being more likely to accumulate a sleep debt during the week and to have greater sleep extension on weekend nights. The aim of the present study was to evaluate the independent contributions of circadian phase and weekend-to-weekday variability to sleep timing in daily life. The study included 14 morning types and 14 evening types recruited from a community-based sample of New Zealand adults (mean age 41.1 ± 4.7 years). On days 1–15, the participants followed their usual routines in their own homes and daily sleep start, midpoint and end times were determined by actigraphy and sleep diaries. Days 16–17 involved a 17 h modified constant routine protocol in the laboratory (17:00 to 10:00, <20 lux) with half-hourly saliva samples assayed for melatonin. Mixed model ANCOVAs for repeated measures were used to investigate the independent relationships between sleep start and end times (separate models) and age (30–39 years versus 40–49 years), circadian phase [time of the dim light melatonin onset (DLMO)] and weekday/weekend schedules (Sunday–Thursday nights versus Friday–Saturday nights). As expected on weekdays, evening types had later sleep start times (mean = 23:47 versus 22:37, p < .0001) and end times (mean = 07:14 versus 05:56, p < .0001) than morning types. Similarly on weekend days, evening types had later sleep start times (mean = 00:14 versus 23:07, p = .0032) and end times (mean = 08:56 versus 07:04, p < .0001) than morning types. Evening types also had later DLMO (22:06 versus 20:46, p = .0002) than morning types (mean difference = 80.4 min, SE = 18.6 min). The ANCOVA models found that later sleep start times were associated with later DLMO (p = .0172) and weekend-to-weekday sleep timing variability (p < .0001), after controlling for age, while later sleep end times were associated with later DLMO (p = .0038), younger age (p = .0190) and weekend days (p < .0001). Sleep end times showed stronger association with DLMO (for every 30 min delay in DLMO, estimated mean sleep end time occurred 14.0 min later versus 10.19 min later for sleep start times). Sleep end times also showed greater delays on weekends versus weekdays (estimated mean delay for sleep end time = 84 min, for sleep start time = 28 min). Comparing morning types and evening types, the estimated contributions of the DLMO to the mean observed differences in sleep timing were on weekdays, 39% for sleep start times and 49% for sleep end times; and on weekends, 41% for sleep start times and 34% of sleep end times. We conclude that differences in sleep timing between morning types and evening types were much greater than would be predicted on the basis of the independent contribution of the difference in DLMO on both weekdays and weekend days. The timing of sleep in daily life involves complex interactions between physiological and psychosocial factors, which may be moderated by age in adults aged 30–49 years.     

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2)?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.     

Effect of evening exposure to dim or bright light on the digestion of carbohydrate in the supper meal

In a previous study we found that daytime exposure to bright as compared to dim light exerted a beneficial effect on the digestion of the evening meal. This finding prompted us to examine whether the digestion of the evening meal is also affected by evening light intensity. Subjects lived in light of 200 lux during the daytime (08:00-17:00 h) and took their evening meal at 17:00 h under 20 lux (evening dim-light condition: 17:00-02:00 h) or 2000 lux (evening bright-light condition: 17:00-02:00 h) until retiring at 02:00 h. Assessment of carbohydrate digestion of the evening meal was accomplished by a breath hydrogen test that is indicative of the malabsorption of dietary carbohydrate. Hydrogen excretion in the breath in the evening under the dim-light condition was significantly less than under the bright-light condition (p < 0.05). This finding is the opposite to that obtained in previous experiments in which subjects were exposed to the different intensities of light during the daytime, and indicates that the exposure to dim light in the evening exerts a better effect on carbohydrate digestion in the evening meal than does the exposure to bright light.     

CIRCADIAN RHYTHMICITY OF CORTISOL AND BODY TEMPERATURE: MORNINGNESS-EVENINGNESS EFFECTS

The purpose of this study was to describe and compare the circadian rhythm of body temperature and cortisol, as well as self-reported clock times of sleep onset and offset on weekdays and weekends in 19 healthy adult “larks” (morning chronotypes) and “owls” (evening chronotypes), defined by the Horne and Östberg questionnaire. Day-active subjects entered the General Clinical Research Center, where blood was sampled every 2h over 38h for later analysis for cortisol concentration by enzyme immunoassay. Rectal body temperature was measured continuously. Lights were turned off at 22:30 for sleep and turned on at 06:00, when subjects were awakened. The acrophases (peak times) of the cortisol and temperature rhythms occurred 55 minutes (P ≤.05) and 68 minutes (P <.01), respectively, earlier in the morningness group. The amplitude of the cortisol rhythm was lower in the eveningness than in the morningness group (P = n.s.). Subject groups differed on all indices of habitual and preferred timing of sleep and work weekdays and weekends (P =. 05–.001). (Chronobiology International, 18(2), 249–261, 2001)     

Older Poor-Sleeping Women Display a Smaller Evening Increase in Melatonin Secretion and Lower Values of Melatonin and Core Body Temperature Than Good Sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62–72 yrs) and 9 older good-sleeping women (60–82 yrs) were compared with 10 younger good-sleeping women (23–28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R²?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people. (Author correspondence: mdittmar@zoologie.uni-kiel.de)     

Differences in Sleep,Light, and Circadian Phase in Offshore 18:00–06:00 h and 19:00–07:00 h Shift Workers

Complaints concerning sleep are high among those who work night shifts; this is in part due to the disturbed relationship between circadian phase and the timing of the sleep‐wake cycle. Shift schedule, light exposure, and age are all known to affect adaptation to the night shift. This study investigated circadian phase, sleep, and light exposure in subjects working 18:00–06:00 h and 19:00–07:00 h schedules during summer (May–August). Ten men, aged 46±10 yrs (mean±SD), worked the 19:00–07:00 h shift schedule for two or three weeks offshore (58°N). Seven men, mean age 41±12 yrs, worked the 18:00–06:00 h shift schedule for two weeks offshore (61°N). Circadian phase was assessed by calculating the peak (acrophase) of the 6‐sulphatoxymelatonin rhythm measured by radioimmunoassay of sequential urine samples collected for 72 h at the end of the night shift. Objective sleep and light exposure were assessed by actigraphy and subjective sleep diaries. Subjects working 18:00–06:00 h had a 6‐sulphatoxymelatonin acrophase of 11.7±0.77 h (mean±SEM, decimal hours), whereas it was significantly later, 14.6±0.55 h (p=0.01), for adapted subjects working 19:00–07:00 h. Two subjects did not adapt to the 19:00–07:00 h night shift (6‐sulphatoxymelatonin acrophases being 4.3±0.22 and 5.3±0.29 h). Actigraphy analysis of sleep duration showed significant differences (p=0.03), with a mean sleep duration for those working 19:00–07:00 h of 5.71±0.31 h compared to those working 18:00–06:00 h whose mean sleep duration was 6.64±0.33 h. There was a trend to higher morning light exposure (p=0.07) in the 19:00–07:00 h group. Circadian phase was later (delayed on average by 3 h) and objective sleep was shorter with the 19:00–07:00 h than the 18:00–06:00 h shift schedule. In these offshore conditions in summer, the earlier shift start and end time appears to favor daytime sleep.     

Melatonin Treatment Effects on Adolescent Students' Sleep Timing and Sleepiness in a Placebo-Controlled Crossover Study

During the last few decades, the incidence of sleep-onset insomnia, due to delay of circadian phase, has increased substantially among adolescents all over the world. We wanted to investigate whether a small dose of melatonin given daily, administered in the afternoon, could advance the sleep timing in teenagers. Twenty-one students, aged 14–19 yrs, with sleep-onset difficulties during school weeks were recruited. The study was a randomized, double blind, placebo (PL)-controlled crossover trial, lasting 5 wks. During the first 6 d in wks 2 and 4, the students received either PL or melatonin (1 mg) capsules between 16:30 and 18:00 h. During the first 6 d of wk 5, all students received melatonin. Wks 1 and 3 were capsule-free. In the last evening of each week and the following morning, the students produced saliva samples at home for later melatonin analysis. The samples were produced the same time each week, as late as possible in the evening and as early as possible in the morning. Both the student and one parent received automatic mobile text messages 15 min before saliva sampling times and capsule intake at agreed times. Diaries with registration of presumed sleep, subjective sleepiness during the day (Karolinska Sleepiness Scale, KSS) and times for capsule intake and saliva samplings were completed each day. Primary analysis over 5 wks gave significant results for melatonin, sleep and KSS. Post hoc analysis showed that reported sleep-onset times were advanced after melatonin school weeks compared with PL school weeks (p < .005) and that sleep length was longer (p < .05). After the last melatonin school week, the students fell asleep 68 min earlier and slept 62 min longer each night compared with the baseline week. Morning melatonin values in saliva diminished compared with PL (p < .001) and evening values increased (p < .001), indicating a possible sleep phase advance. Compared with PL school weeks, the students reported less wake up (p < .05), less school daytime sleepiness (p < .05) and increased evening sleepiness (p < .005) during melatonin weeks. We conclude that a small dose of melatonin given daily, administered in the afternoon, could advance the sleep timing and make the students more alert during school days even if they continued their often irregular sleep habits during weekends. (Author correspondence: arne.lowden@stress.su.se)     

Theophylline Dose-Concentration Relationship of a 12-Hourly Nuelin SA Regimen Supplemented with Nocturnal Nuelin Liquid in Healthy Volunteers

Twelve healthy male volunteers who were diurnally active between 05:00 and 23:00 took part in a randomized, multiple-dose, double-blind, four-way, crossover study to determine the relationship between the dose of a nonsus-tained-release theophylline (NSRT) formulation added to the evening administration of a 12-hourly sustained-release theophylline (SRT) regimen and the elevation of the early morning (between 02:00 and 05:00) steady-state plasma theophylline concentration. The four treatments were 250 mg Nuelin SA (sustained-release theophylline) every 12 h plus either placebo or Nuelin liquid (non-sustained-release theophylline) equivalent to 100 mg, 200 mg, or 300 mg of theophylline. Without evening supplementation (placebo), the early morning plasma theophylline concentrations were 13% lower than the average 24-h concentration. but with evening supplementation the early morning plasma theophylline concentration could be raised up to and above the average 24-h Concentration. A prediction equation for the early morning plasma theophylline concentration as a function of the additional evening dose of Nuelin liquid, and of the steady-state evening trough plasma theophylline concentration without evening supplementation, was established. This prediction equation can be used to determine the additional evening dose of Nuelin liquid (administered at 19:00) needed to reduce early morning bronchoconstriction in asthmatic patients who are on a 12-hourly Nuelin SA (drug administered at 07:00 and 19:00) regimen.     

Differences in sleep, light, and circadian phase in offshore 18:00-06:00 h and 19:00-07:00 h shift workers

Complaints concerning sleep are high among those who work night shifts; this is in part due to the disturbed relationship between circadian phase and the timing of the sleep-wake cycle. Shift schedule, light exposure, and age are all known to affect adaptation to the night shift. This study investigated circadian phase, sleep, and light exposure in subjects working 18:00-06:00 h and 19:00-07:00 h schedules during summer (May-August). Ten men, aged 46+/-10 yrs (mean+/-SD), worked the 19:00-07:00 h shift schedule for two or three weeks offshore (58 degrees N). Seven men, mean age 41+/-12 yrs, worked the 18:00-06:00 h shift schedule for two weeks offshore (61 degrees N). Circadian phase was assessed by calculating the peak (acrophase) of the 6-sulphatoxymelatonin rhythm measured by radioimmunoassay of sequential urine samples collected for 72 h at the end of the night shift. Objective sleep and light exposure were assessed by actigraphy and subjective sleep diaries. Subjects working 18:00-06:00 h had a 6-sulphatoxymelatonin acrophase of 11.7+/-0.77 h (mean+/-SEM, decimal hours), whereas it was significantly later, 14.6+/-0.55 h (p=0.01), for adapted subjects working 19:00-07:00 h. Two subjects did not adapt to the 19:00-07:00 h night shift (6-sulphatoxymelatonin acrophases being 4.3+/-0.22 and 5.3+/-0.29 h). Actigraphy analysis of sleep duration showed significant differences (p=0.03), with a mean sleep duration for those working 19:00-07:00 h of 5.71+/-0.31 h compared to those working 18:00-06:00 h whose mean sleep duration was 6.64+/-0.33 h. There was a trend to higher morning light exposure (p=0.07) in the 19:00-07:00 h group. Circadian phase was later (delayed on average by 3 h) and objective sleep was shorter with the 19:00-07:00 h than the 18:00-06:00 h shift schedule. In these offshore conditions in summer, the earlier shift start and end time appears to favor daytime sleep.     

Theophylline Dose-Concentration Relationship of a 12-Hourly Nuelin SA Regimen Supplemented with Nocturnal Nuelin Liquid in Healthy Volunteers

Twelve healthy male volunteers who were diurnally active between 05:00 and 23:00 took part in a randomized, multiple-dose, double-blind, four-way, crossover study to determine the relationship between the dose of a nonsus-tained-release theophylline (NSRT) formulation added to the evening administration of a 12-hourly sustained-release theophylline (SRT) regimen and the elevation of the early morning (between 02:00 and 05:00) steady-state plasma theophylline concentration. The four treatments were 250 mg Nuelin SA (sustained-release theophylline) every 12 h plus either placebo or Nuelin liquid (non-sustained-release theophylline) equivalent to 100 mg, 200 mg, or 300 mg of theophylline. Without evening supplementation (placebo), the early morning plasma theophylline concentrations were 13% lower than the average 24-h concentration. but with evening supplementation the early morning plasma theophylline concentration could be raised up to and above the average 24-h Concentration. A prediction equation for the early morning plasma theophylline concentration as a function of the additional evening dose of Nuelin liquid, and of the steady-state evening trough plasma theophylline concentration without evening supplementation, was established. This prediction equation can be used to determine the additional evening dose of Nuelin liquid (administered at 19:00) needed to reduce early morning bronchoconstriction in asthmatic patients who are on a 12-hourly Nuelin SA (drug administered at 07:00 and 19:00) regimen.     

Relationship of chronotype to sleep, light exposure, and work-related fatigue in student workers

Students who work during the school year face the potential of sleep deprivation and its effects, since they have to juggle between school and work responsibilities along with social life. This may leave them with less time left for sleep than their nonworking counterparts. Chronotype is a factor that may exert an influence on the sleep of student workers. Also, light and social zeitgebers may have an impact on the sleep-related problems of this population. This study aimed to document sleep, light exposure patterns, social rhythms, and work-related fatigue of student workers aged 19-21 yrs and explore possible associations with chronotype. A total of 88 student workers (mean ± SD: 20.18 ± .44 yrs of age; 36 males/52 females) wore an actigraph (Actiwatch-L; Mini-Mitter/Respironics,Bend, OR) and filled out the Social Rhythm Metric for two consecutive weeks during the school year. Also, they completed the Morningness-Eveningness Questionnaire (MEQ), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Occupational Fatigue Exhaustion/Recovery Scale (OFER). Repeated and one-way analyses of variance (ANOVAs), Pearson's chi-square tests, and correlation coefficients were used for statistical comparisons. Subjects slept an average of 06:28 h/night. Actigraphic sleep parameters, such as sleep duration, sleep efficiency, wake after sleep onset, and sleep latency, did not differ between chronotypes. Results also show that evening types (n = 17) presented lower subjective sleep quality than intermediate types (n = 58) and morning types (n = 13). Moreover, evening types reported higher levels of chronic work-related fatigue, exhibited less regular social rhythms, and were exposed to lower levels of light during their waking hours (between 2 and 11 h after wake time) as compared to intermediate types and morning types. In addition, exposure to light intensities between 100 and 500 lux was lower in evening types than in intermediate types and morning types. However, bright light exposure (≥ 1000 lux) did not differ between chronotypes. In conclusion, results suggest that student workers may constitute a high-risk population for sleep deprivation. Evening types seemed to cope less well with sleep deprivation, reporting poorer sleep quality and higher levels of work-related fatigue than intermediate types and morning types. The higher chronic work-related fatigue of evening types may be linked to their attenuated level of light exposure and weaker social zeitgebers. These results add credence to the hypothesis that eveningness entails a higher risk of health-impairing behaviors.     

Shifts of the hormonal rhythms of melatonin and cortisol after a 4 h bright‐light pulse in different diurnal types

If applied during corresponding times of the individual melatonin profiles, bright light shifts the circadian phase equally, irrespective of diurnal type. We examined 32 young men: 10 morning types, 11 evening types, and 11 with no predisposition; 16 with high and 16 with low melatonin production. Each completed a 40 h session that included two consecutive nights during which the participants remained, apart from two short breaks during the second day, in bed under an illumination level of 30 lux. A 4 h bright light pulse was applied just after the expected individual melatonin onset the first night to cause a delay of the hormonal profile the second night. Salivary levels of melatonin and cortisol were determined hourly. Melatonin was delayed by 108 min, and cortisol offset and onset by 47 and 110 min, respectively. The cortisol quiescent period (start and end of the quiescent period being defined by the decrease below and the increase above 60% of the average cortisol production between 18:00 and 09:00 h) was prolonged. In contrast to the other subgroups, the delay of melatonin synthesis was about 0.5 h shorter in morning types, and their cortisol quiescent period was shortened. The present study leads to the hypothesis that, despite individually scheduled light exposure, morning types are potentially disadvantaged due to elevated cortisol levels, if persisting, in career night workers.     

Ring the bell for Matins: circadian adaptation to split sleep by cloistered monks and nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39 ± 4:30 h (median ± 95% interval), plateau or rise of temperature at 22:35 ± 00:23 h (while asleep) lasting 296 ± 39 min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85 ± 15 min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05 ± 00:59 h vs. 00:00 ± 00:54 h, median ± 95% confidence interval, p= .0001) and offset (06:27 ± 0:22 h, vs. 07:37 ± 0:33 h, p= .0001), as well as a shorter sleep time (6.5 ± 0.6 vs. 7.6 ± 0.7 h, p= .05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time.     

Shifts of the hormonal rhythms of melatonin and cortisol after a 4 h bright-light pulse in different diurnal types

If applied during corresponding times of the individual melatonin profiles, bright light shifts the circadian phase equally, irrespective of diurnal type. We examined 32 young men: 10 morning types, 11 evening types, and 11 with no predisposition; 16 with high and 16 with low melatonin production. Each completed a 40 h session that included two consecutive nights during which the participants remained, apart from two short breaks during the second day, in bed under an illumination level of 30 lux. A 4 h bright light pulse was applied just after the expected individual melatonin onset the first night to cause a delay of the hormonal profile the second night. Salivary levels of melatonin and cortisol were determined hourly. Melatonin was delayed by 108 min, and cortisol offset and onset by 47 and 110 min, respectively. The cortisol quiescent period (start and end of the quiescent period being defined by the decrease below and the increase above 60% of the average cortisol production between 18:00 and 09:00 h) was prolonged. In contrast to the other subgroups, the delay of melatonin synthesis was about 0.5 h shorter in morning types, and their cortisol quiescent period was shortened. The present study leads to the hypothesis that, despite individually scheduled light exposure, morning types are potentially disadvantaged due to elevated cortisol levels, if persisting, in career night workers.