Dr. Joan Saary, MD, MSc, PhD, FRCPC, CIP, FACOEM Assistant Professor of Medicine, University of Toronto OEMAC Conference, Toronto, Sept 28, 2015

Transcription

1 Dr. Joan Saary, MD, MSc, PhD, FRCPC, CIP, FACOEM Assistant Professor of Medicine, University of Toronto OEMAC Conference, Toronto, Sept 28, 2015

2 DISCLOSURE OF COMMERCIAL SUPPORT Potential for conflict(s) of interest: - Joan Saary has not received payment/funding, etc. from any organization whose product(s) are being discussed in this program

3 FACULTY/PRESENTER DISCLOSURE Faculty: Joan Saary Relationships with commercial interests: - Grants/Research Support: none - Speakers Bureau/Honoraria: none - Consulting Fees: none - Other: none

4 Learning Objectives 1) As a mechanism to enhance recollection, the learner will be able extrapolate some of the health effects of shiftwork by understanding the basic physiology of circadian rhythms. 2) The learner will enhance his/her knowledge of the inter-related concepts of sleep, circadian rhythms and shiftwork by gaining awareness of current research, including newsworthy topics such as blue light and e-readers 3) Through exposure to current information on strategies for enabling circadian adaptation and mitigating health risks, the learner will be able to formulate management strategies relevant to groups of workers in their own practice as well as individuals requesting restrictions. JSaary, Oct

5 Are you an average teen? The average teenager spends how many hours engaged in recreational media use? JSaary, Oct

6 Are you an average teen? The average teenager spends how many hours engaged in recreational media use? 7.5 hours JSaary, Oct

7 Neurological Conditions Associated with Sleep Loss (<7-8 hrs/night) Cerebrovascular disease Alzheimer s disease Parksinson s disease Multiple sclerosis Epilepsy Headache disorders Somnambulism and nightmares Pain JSaary, Oct

8 JSaary, Oct

9 National Sleep Foundation 2015 Updated Recommendations Teenagers (14-17): Sleep range widened by one hour to 8 to 10 hours previously 8.5 to 9.5 hrs Younger adults (18-25): new age category Sleep range is 7 to 9 hours Adults (26-64): Remains 7 to 9 hours Older adults (65+): new age category Sleep range is 7 to 8 hours JSaary, Oct

10 Circadian Rhythms Many human functions oscillate within a 24 hour framework including: Physiologic processes (eg metabolism) Psychological Processes (eg short-term memory) Social Processes (eg family interaction) The body clock or circadian pacemaker is situated in suprachiasmatic nucleus of hypothalamus which controls the timings of: sleep-wake cycle, alertness and performance rhythms, hormone production, temperature regulation, metabolism. JSaary, Oct

11 Cajochen et al. Am J Physiol 1999

12 Entrainment Daily 24-hour light-dark cycle is required to entrain to a 24 hour day Most totally blind people cannot remain entrained to 24 hours 750 Non-entrained Days 5-6 A 1 0 Days y No light perception = h Study day amt6s (ng/h) 750 Days Days Days Clock time (h) Sleep-wake cycle 0 Clock time (h) Urinary melatonin Lockley et al., Dialogues Clin Neurosci 2007

13 Incomplete Entrainment With changing shifts, each of the circadian rhythms adapt, but at its own rate = dyssynchrony

14 Some Causes of Incomplete Entrainment in Shift Workers 1. Reversion to daytime schedules on days off 2. Exposure to light at the end of the shift 3. Short rotation schedules don t leave enough adaptation time: readjustment for complete cycle inversion takes several weeks, not days

15 Another Cause of Incomplete Entrainment JSaary, Oct

16 Citation: Cancer Care Ontario. Cancer Fact: Shift work in Canadian industries a probable cancer risk factor. March Available at Prepared by staff in the Occupational Cancer Research Centre in Prevention and Cancer Control.

17 Who Can Stand Shiftwork? 20% of workers have to stop shiftwork altogether after a very brief period because of health problems 10% do not complain about shiftwork during their whole working life 70% withstand shiftwork with different levels of intolerance that can become more or less manifest at different times and with different intensity in terms of discomforts, troubles or diseases Waterhouse et al., 1992

18 Circadian Photoreception Much like the ear has dual functions for audition and balance, the human eye has a dual role in detecting light for a range of behavioral and physiological responses separate and apart from sight These non-visual effects of light are mediated by non-rod, non-cone photoreceptors in the ganglion cell layer of the eye These photosensitive ganglion cells contain a photopigment (melanopsin) to detect light Maximally sensitive to short-wavelength (blue) visible light ( max ~480 nm) JSaary, Oct

19 Intrinsically Photosensitive Retinal Ganglion Cells (iprgcs) A type of neuron in the mammalian retina discovered in 2007 although they were found in mice earlier, and the effect was known well before that Small subset of retinal ganglion cells (1%) unlike other ganglion cells because they are photosensitive Contain melanopsin Respond to light even when rods and cones do not function Send light information via the retino-hypothalamic tract to the supra-chiasmatic nucleus JSaary, Oct

20 Suprachiasmatic Nucleus - SCN Located in the hypothalamus Capacity for light-induced gene expression Info from SCN is sent to other hypothalamic nuclei to regulate functions with circadian rhythmicity such as body temperature and hormone production eg cortisol, melatonin JSaary, Oct

21 Melatonin and Light Our biological clocks use light as a marker Melatonin is the hormone which regulates circadian rhythms Melatonin is produced in the absence of light (i.e. in darkness) Melatonin induces sleepiness and lowers core temperature Sun goes down, melatonin rises to nocturnal levels Sun rises, melatonin falls to very low daytime levels Melatonin = night = sleepy Trying to sleep during the day is difficult (since low or no melatonin in blood) JSaary, Oct

22 Dose -Response Melatonin suppression is proportional to: light intensity length of exposure JSaary, Oct

23 Dose- Response - Irradiance Response curve was developed for plasma melatonin suppression in subjects exposed to a range of irradiances of blue LED light. Blood melatonin samples were collected before and after light exposures between 2:00 and 3:30 am Increasing irradiances of narrow band blue-appearing light can elicit increasing plasma melatonin suppression Narrow bandwidth blue LED light may be stronger than white fluorescent light currently used in most general lighting fixtures for suppressing melatonin. West et al. Journal of Applied Physiology 2011; 110(3): JSaary, Oct

24 Maximally Sensitive to Blue Melatonin shuts off in the daytime with blue light, around 460 to 480 nm Blue light = daytime Blue-blocking = nighttime JSaary, Oct

25 Lux vs Lambda (λ) JSaary, Oct

26 Effect of Wavelength Volunteers were randomly allocated to one of four conditions of equal luminance: light box, white LED, blue/green LED, no light/ control group. The experimental groups showed significant melatonin suppression with the blue/green LEDs producing the greatest (70%) suppression. There was no significant difference between the light box at 63% and white LED at 50% suppression. Similarly, the blue/green LED had a significantly greater delay in melatonin release of 42 min and no difference between the light box of 23 min and the white LED of 22 min. Wright et al. Journal of Pineal Research 2001; 31(4): JSaary, Oct

27 Sensing Light in Blindness A small percentage of blind individuals retain non-image-forming photoreception Such patients can choose non-randomly about the presence of light 2 sec of blue light modified EEG activity fmri showed that < 1 min of blue light triggered the recruitment of supplemental prefrontal and thalamic brain regions involved in alertness and cognition regulation. Conclusion: Light stimulates higher cognitive brain activity, independently of vision, and engages supplemental brain areas to perform an ongoing cognitive process. Vandewalle et al. Journal of Cognitive Neuroscience 2013; 25(12): JSaary, Oct

28 Cataracts Reduced blue-light transmission through cataract impairs non-visual brain responses Researchers have tested for changes in reaction time following cataract surgery and intraocular lens implantation. Responses became both quicker and more consistent following surgery, with statistically significant improvements which were not due to a learning effect or improved vision. CONCLUSION: Improved blue-light transmission following cataract surgery has a beneficial effect on cognitive function. Schmoll et al. British Journal of Ophthalmology 2011; 95(12): JSaary, Oct

29 Lens Aging Reduced transmission of blue light to the retina reduced because of aging of the lens may impair the photo-entrainment of circadian rhythm leading to sleep disorders. Researchers studied the association between lens aging and sleep disorders. Sleep disturbances were evaluated by a combination of questionnaire and the use of prescription sleeping medication. Lens aging was measured objectively by lens autofluorometry The risk of sleep disturbances was significantly increased when the transmission of blue light to the retina was low, even after correction for the effect of age and other confounding factors such as smoking habits, diabetes mellitus, gender, and the risk of ischemic heart disease (P < ). Kessel et al. Sleep 2011; 34(9): JSaary, Oct

30 Aging Using f-mri to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light: the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. CONCLUSION: The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. JSaary, Oct 2015 Daneault et al. Sleep 2014; 37(1):

31 Genetics and Circadian Rhythms 1960s: Oscillating rhythms were found to be genetically regulated (Pittendrigh, 1967). 1980s: The first circadian gene, Period, was cloned from fruit flies (Bargiello et al.,1984; Reddy et al., 1984). Many circadian genes have since been identified Numerous gene products that function in interacting feedback loops have been identified in all species studied. There is survival advantage in having a biological clock because behaviour and physiology can be organized around cyclic changes in the environment. JSaary, Oct

32 Period3 Polymorphisms Per3 is a clock gene Polymorphisms in this gene affect both subjective and objective response to light Individuals homozygous for the longer allele of PER3 (PER35/5) appear to be more sensitive to blue-enriched light than carriers of the shorter allele (PER34/4). Their subjective perception was that light was brighter, and objectively they had higher levels of occipital NREM sleep throughout the entire sleep episode, following light exposure at 6500 K. Light at 6500 K attenuated endogenous melatonin and enhanced the alerting response to light, with less subjective sleepiness and waking EEG theta activity (5 7 Hz), only in PER35/5 individuals The more blue light is perceived as bright, the more the occipital cortex may be engaged during light exposure. Chellappa et al, Behavioural Brain Research 2014; 271: JSaary, Oct 2015

33 Per2 Gene Expression Measurement of PER2 gene expression in oral mucosa samples demonstrated circadian oscillation Induction of human PER2 expression is stimulated by exposing subjects to 2 h of blue (460 nm) but not green (550 nm) light in the evening statistically moreso than a non-light control condition Cajochen et al. European Journal of Neuroscience 2006; 23(4): JSaary, Oct

34 Energy Efficiency Trade Off Compared to an incandescent lamp and daylight, typical energy savers spectra contain multiple sharp peaks and dips. JSaary, Oct

35 Too Much Daytime Too much daytime = too much blue 2 problematic circumstances: making daytime at night needing nighttime during the day JSaary, Oct

36 Are You Typical? What percentage of people used some type of electronics at least a few nights per week within 1 h before bedtime? in a recent representative survey of 1,508 American adults JSaary, Oct

37 Are You Typical? What percentage of people used some type of electronics at least a few nights per week within 1 h before bedtime? 90% JSaary, Oct

38 Effect of Electronics Before Bed Sustained alertness Interruptions from wakeup calls from chimes, reminders, etc Suppression of melatonin JSaary, Oct

39 E-reader vs ipad The ipad and traditional computer screens use a back-lit display emitting light of its own An e-paper screen reflects ambient light like a real book would. This makes e-paper devices easy to view even in direct sunlight. The reason for concern with the ipad over other forms of late-night light is that readers hold the device relatively close to their face JSaary, Oct

40 Peaks at 452 nm are in the blue light range, compared with broad-spectrum light (white light), with a peak at 612 nm. JSaary, Oct

41 LE-eBook vs Print Compared to reading a printed book, participants reading an LE-eBook: took longer to fall asleep got less REM sleep had reduced evening sleepiness, AND reduced next morning alertness taking hours longer to fully wake up had reduced melatonin secretion by 55% (± 20%) compared to no suppression Chang, A-M et al. PNAS 2015; 112(4): JSaary, Oct

42 The Next Day: You ll Pay Subjects were exposed either to blue LEDs or to no light for 2 h in the evening. During sleep, sleep architecture and alpha and delta power of EEG were similar in the two experimental conditions. Exposure to low intensity blue light in the evening, which did not affect sleep architecture and energy metabolism during sleep, elicited drowsiness and suppression of energy metabolism the following morning. Kayaba et al. Environ Health Prev Med 2014;19(5): JSaary, Oct

43 Backlighting Researchers compared the effects of evening exposure to a white LED-backlit screen with more than twice as much 464 nm light emission than a white non-ledbacklit screen on melatonin, alertness, and cognitive performance levels Compared to non-led-backlit the white LED-backlit screen elicited: a significant suppression of the evening rise in endogenous melatonin reduced subjective sleepiness reduced objective sleepiness measured by a reduced incidence of slow eye movements and EEG low-frequency activity (1-7 Hz) in frontal brain regions. Cajochen et al. Journal of Applied Physiology 2011; 110(5): JSaary, Oct

44 Comparison to Hypnotics There is a 10-min-shorter sleep latency with print-books compared to the LE-eBook The effect size is similar to that of eszopiclone treatment on sleep latency in patients with primary insomnia Conclusion Krystal AD, et al. Prim Care Companion CNS Disord 2012; 14(4). JSaary, Oct

45 Solutions for Too Much Blue JSaary, Oct

46 NSF Recommendations Stick to a sleep schedule, even on weekends Practice a relaxing bedtime ritual Exercise daily Evaluate your bedroom to ensure ideal temperature, sound and light (cool, quiet, dark) Sleep on a comfortable mattress and pillows. Beware of hidden sleep stealers, like alcohol and caffeine Turn off electronics before bed JSaary, Oct

47 Harvard Health: Recommendations Use dim red lights for night lights. Avoid looking at bright screens beginning two to three hours before bed. If you work a night shift or use a lot of electronic devices at night, consider wearing blue-blocking glasses. Expose yourself to lots of bright light during the day, which will boost your ability to sleep at night, as well as your mood and alertness during daylight. Harvard Health Letter JSaary, Oct

48 Reducing Device-Caused Blue JSaary, Oct

49 f.lux for Mac JSaary, Oct

50 For Android Phones: JSaary, Oct

51 Physical Barriers JSaary, Oct

52 JSaary, Oct

53 Liquid Sleep When used several hours before sleep melatonin shifts the circadian clock earlier, according to the phase response curve for melatonin in humans, thus promoting earlier sleep onset and morning awakening JSaary, Oct

54 Melatonin Treatment Melatonin (0.5 mg or 3.0 mg) produced partial dose-dependent circadian phase advances and increased daytime sleep in participants who slept in the evening prior to a simulated night shift Sharkey & Eastman. Am J Physiol Regul Integr Comp Physiol 2002; 282: R454 R463 JSaary, Oct

55 Strategic Napping Two types of strategic napping have been identified: prophylactic naps planned in the evening prior to the shift to limit anticipated sleep deprivation recuperative naps taken at night to temporarily relief sleepiness. Prophylactic and recuperative naps increase total sleep time during the day and improve alertness and performance at work Boivin &Tremblay. Sleep Med 2007; 8: Fallis et al. Crit Care Nurse 2011; 31: e1 e11 JSaary, Oct

56 Monitoring Technology The use of sleepiness monitoring technologies at work has been proposed to prevent accidents and errors related to shift work. However, often alert workers when drowsiness is already present. Ideally part of a comprehensive fatigue management program. Golz et al. Somnologie 2010; 14: JSaary, Oct

57 Spectral Modulation through Optical Light Filtering JSaary, Oct

58 Lenses Volunteers were randomized to wear either blueblocking (amber) or yellow-tinted (blocking ultraviolet only) safety glasses for 3 h prior to sleep for 2 weeks. At the end of the study, the amber lens group experienced significant improvement in sleep quality Mood also improved significantly relative to controls. Burkhart & Phelps. Chronobiology International 2009; 26(8): JSaary, Oct

59 JSaary, Oct

60 Selective Removal of Short λ In animals and humans, selectively removing short wavelengths from nocturnal illumination: prevents melatonin suppression induced by light exposure at night prevents cortisol elevation prevents circadian disruption of clock gene expression Per2 and Bmal No differences in alertness, sleepiness, fatigue, or vigilance Improved sleep duration and quality by polysomnography on nights immediately following night shifts. Improvement in mood and cognitive performance toward the end of the night shift with the use of the optical filters as well. Casper & Rahman. Fertility & Sterility 2014; 102(2): JSaary, Oct

61 JSaary, Oct

62 Combination A strategy based on: blue-green light at night orange-tinted goggles in the morning Resulted in increased daytime sleep by min/day in small groups of shift workers Boivin & Boudreau. Pathologie Biologie 2014; 62(5): JSaary, Oct

63 Passive Phototherapy Volunteers were exposed during sleep to either darkness or a sequence of 2-msec light flashes given every 30 sec from hours 2 to 3 after habitual bedtime Exposing sleeping individuals to 0.24 sec of light spread over an hour shifted the timing of the circadian clock and did so without major alterations to sleep itself. Confirmation that the flashes penetrated the eyelids is presented by the occurrence of an evoked response in the EEG. The future: Passive phototherapy treatment...? Zeitzer et al. Journal of Biological Rhythms. 2014; 29(5): JSaary, Oct

64 2 sides to every coin JSaary, Oct

65 The Flipside JSaary, Oct

66 The Flipside People who spend most of the day indoors (offices etc.) and are often lacking the necessary blue light exposure. Blue and cool white light sources can be used to create lighting conditions such that people will receive their daily portion of blue light to keep their physiology in tune with the natural day night rhythm. NSBRI is examining whether blue-enriched white-appearing light can be used to enhance waking performance Elizabeth Klerman at Harvard-Brigham and Women's Hospital has demonstrated significant circadian phase shifting with an ultra-short two-minute bright light stimulus and is studying the effect of multiple intermittent two-minute exposures within a 6.5-hour time window JSaary, Oct

67 ISS DLS: Dynamic Lighting Schedule Lighting on ISS needs replacing unique opportunity three pre-determined settings to address different operational needs: 1. white light for general vision; 2. blue-enriched white light to enhance high circadian adaptation and alertness; and, 3. blue-depleted white light to minimize alertness prior to sleep JSaary, Oct

68 Learning Objectives 1) As a mechanism to enhance recollection, the learner will be able extrapolate some of the health effects of shiftwork by understanding the basic physiology of circadian rhythms. 2) The learner will enhance his/her knowledge of the inter-related concepts of sleep, circadian rhythms and shiftwork by gaining awareness of current research, including newsworthy topics such as blue light and e-readers 3) Through exposure to current information on strategies for enabling circadian adaptation and mitigating health risks, the learner will be able to formulate management strategies relevant to groups of workers in their own practice as well as individuals requesting restrictions. JSaary, Oct

69 Questions and Discussion JSaary, Oct