Circadian-Related Sleep Disorders and Sleep Medication Use in the New Zealand Blind Population: An Observational Prevalence Survey

STUDY OBJECTIVES: To determine the prevalence of self-reported circadian-related sleep disorders, sleep medication and melatonin use in the New Zealand blind population. DESIGN: A telephone survey incorporating 62 questions on sleep habits and medication together with validated questionnaires on sleep quality, chronotype and seasonality. PARTICIPANTS: PARTICIPANTS WERE GROUPED INTO: (i) 157 with reduced conscious perception of light (RLP); (ii) 156 visually impaired with no reduction in light perception (LP) matched for age, sex and socioeconomic status, and (iii) 156 matched fully-sighted controls (FS). SLEEP HABITS AND DISTURBANCES: The incidence of sleep disorders, daytime somnolence, insomnia and sleep timing problems was significantly higher in RLP and LP compared to the FS controls (p<0.001). The RLP group had the highest incidence (55%) of sleep timing problems, and 26% showed drifting sleep patterns (vs. 4% FS). Odds ratios for unconventional sleep timing were 2.41 (RLP) and 1.63 (LP) compared to FS controls. For drifting sleep patterns, they were 7.3 (RLP) and 6.0 (LP). MEDICATION USE: Zopiclone was the most frequently prescribed sleep medication. Melatonin was used by only 4% in the RLP group and 2% in the LP group. CONCLUSIONS: Extrapolations from the current study suggest that 3,000 blind and visually impaired New Zealanders may suffer from circadian-related sleep problems, and that of these, fewer than 15% have been prescribed melatonin. This may represent a therapeutic gap in the treatment of circadian-related sleep disorders in New Zealand, findings that may generalize to other countries

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

&lt;p&gt;Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.&lt;/p&gt; &lt;p&gt;Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.&lt;/p&gt; &lt;p&gt;Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.&lt;/p&gt; &lt;p&gt;Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.&lt;/p&gt

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

Pathophysiology and pathogenesis of circadian rhythm sleep disorders

Metabolic, physiological and behavioral processes exhibit 24-hour rhythms in most organisms, including humans. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues. The transcription and translation feedback loops of multiple clock genes are involved in the molecular mechanism of the circadian system. Disturbed circadian rhythms are known to be closely related to many diseases, including sleep disorders. Advanced sleep phase type, delayed sleep phase type and nonentrained type of circadian rhythm sleep disorders (CRSDs) are thought to result from disorganization of the circadian system. Evaluation of circadian phenotypes is indispensable to understanding the pathophysiology of CRSD. It is laborious and costly to assess an individual's circadian properties precisely, however, because the subject is usually required to stay in a laboratory environment free from external cues and masking effects for a minimum of several weeks. More convenient measurements of circadian rhythms are therefore needed to reduce patients' burden. In this review, we discuss the pathophysiology and pathogenesis of CRSD as well as surrogate measurements for assessing an individual's circadian phenotype

The Impact of Duty Hours on Resident Self Reports of Errors

BACKGROUND: Resident duty hour limitations aim, in part, to reduce medical errors. Residents’ perceptions of the impact of duty hours on errors are unknown. OBJECTIVE: To determine residents’ self-reported contributing factors, frequency, and impact of hours worked on suboptimal care practices and medical errors. DESIGN: Cross-sectional survey. SUBJECTS: 164 Internal Medicine Residents at the University of California, San Francisco. MEASUREMENTS AND RESULTS: Residents were asked to report the frequency and contributing factors of suboptimal care practices and medical errors, and how duty hours impacted these practices and aspects of resident work-life. One hundred twenty-five residents (76%) responded. The most common suboptimal care practices were working while impaired by fatigue and forgetting to transmit information during sign-out. In multivariable models, residents who felt overwhelmed with work (p = 0.02) and who reported spending >50% of their time in nonphysician tasks (p = 0.002) were more likely to report suboptimal care practices. Residents reported work-stress (a composite of fatigue, excessive workload, distractions, stress, and inadequate time) as the most frequent contributing factor to medical errors. In multivariable models, only engaging in suboptimal practices was associated with self-report of higher risk for medical errors (p < 0.001); working more than 80 hours per week was not associated with suboptimal care or errors. CONCLUSION: Our findings suggest that administrative load and work stressors are more closely associated with resident reports of medical errors than the number of hours work. Efforts to reduce resident duty hours may also need to address the nature of residents’ work to reduce errors

Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function

Safety and acceptability of an organic light-emitting diode sleep mask as a potential therapy for retinal disease

Purpose The purpose of the study was to study the effect of an organic light-emitting diode sleep mask on daytime alertness, wellbeing, and retinal structure/function in healthy volunteers and in diabetic macular oedema (DMO). Patients and methods Healthy volunteers in two groups, 18–30 yrs (A), 50–70 yrs (B) and people with DMO (C) wore masks (504 nm wavelength; 80 cd/m2 luminance; ≤8 h) nightly for 3 months followed by a 1-month recovery period. Changes from baseline were measured for (means): psychomotor vigilance task (PVT) (number of lapses (NL), response time (RT)), sleep, depression, psychological wellbeing (PW), visual acuity, contrast sensitivity, colour, electrophysiology, microperimetry, and retinal thickness on OCT. Results Of 60 participants, 16 (27%) withdrew, 8 (13%) before month 1, due to sleep disturbances and mask intolerance. About 36/55 (65%) who continued beyond month 1 reported ≥1 adverse event. At month 3 mean PVT worsened in Group A (RT (7.65%, P<0.001), NL (43.3%, P=0.005)) and mean PW worsened in all groups (A 28.0%, P=0.01, B 21.2%, P=0.03, C 12.8%, P<0.05). No other clinically significant safety signal was detected. Cysts reduced/resolved in the OCT subfield of maximal pathology in 67% Group C eyes. Thinning was greater at 3 and 4 months for greater baseline thickness (central subfield P<0.001, maximal P<0.05). Conclusion Sleep masks showed no major safety signal apart from a small impairment of daytime alertness and a moderate effect on wellbeing. Masks were acceptable apart from in some healthy participants. Preliminary data suggest a beneficial effect on retinal thickness in DMO. This novel therapeutic approach is ready for large clinical trials

Analysis Method and Experimental Conditions Affect Computed Circadian Phase from Melatonin Data

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P = 0.57), but there were significant differences between those of melatonin offsets (P<0.0001). For a subset of phase assessment methods, we also examined the effects of data loss on variability of phase estimates by systematically removing data in 2-hour segments. Data loss near onset of melatonin secretion differentially affected phase estimates from the methods, with some methods incorrectly assigning phases too early while other methods assigning phases too late; missing data at other times did not affect analyses of the melatonin profile. We conclude that melatonin data set characteristics, including amplitude and completeness of data collection, differentially affect the results depending on the melatonin analysis method used

Association of Sleep Duration with Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Background: In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Methods: Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994–1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. Results: During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-,8 h/day, participants with sleep duration of,6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95