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1

2 Alan presents

3 Restless Nights... on EARTH! Light, Circadian Physiology, and Promoting Alertness CAMA Annual Scientific & Educational Meeting, 9/10/16 -- Alan Kubey, M.D.

4 Disclosures Patent # US B2 Thomas Jefferson University Light Research Program (Dr. Brainard) Harvard Division of Sleep Medicine (Dr. Barger et al.) SSLA Development (NASA/NSBRI/BCM/Wyle)

5 NEED TO KNOW #1 Sleep deprivation and circadian misalignment decrease cognitive and physical performance Not all sleep deprivation and circadian misalignment is created equal There exist several, side-effect free, countermeasures

6 Definitions/Background Circadian Daily Biological Rhythm Internal clock regulates an average circadian rhythm of 24.2 hrs a day Light serves as the strongest external stimulus for maintaining circadian alignment to Earth s 24-hour day/night cycle

7 Phase Shifting Definitions/Background Phase advance shortens circadian cycle (shift to an earlier time for sleep) Phase delay lengthens circadian cycle (shift to a later time for sleep) Circadian Misalignment Desynchronization that results when external cues oppose the internal clock (i.e., light during the night) Traveling across time zones & working overnight lead to circadian misalignment CBT min.

8 Definitions/Background Melatonin: biological darkness signal In the evening and during periods of darkness, melatonin is produced and released into the blood. When melatonin is high at night, alertness dips and the desire to sleep increases Daytime levels of melatonin are barely detectable Bright light inhibits the release of melatonin

9 The Sleep-Deprived Pilot

10 The Sleep-Deprived Pilot

11 The Sleep-Deprived Pilot The macho pilot/astronaut/doctor approach and consequences "My mind clicks on and off... I try letting one eyelid close at a time while I prop the other open with my will. But the effort's too much. Sleep is winning. My whole body argues dully that nothing, nothing life can attain is quite so desirable as sleep. My mind is losing resolution and control. Charles Lindbergh Three Mile Island/Chernobyl/Korean Air Flight 801/Challenger/Exxon Valdez >180,000 patient deaths per year/needle sticks/mvas Sleep Deprivation Timeline: 24 hrs = BAC 0.1% 2-3 Days: Hallucinations 3+ Days: Possible seizures Days: Death

12 The Sleep-Deprived Pilot $2.1b $8.88 $150b $5

13 The Jet-Setting, Shift-Working, Pilot

14 The Jet-Setting, Shift-Working, Pilot A Case study... In SPACE!

15 The Jet-Setting, Shift-Working, Pilot Astronaut Circadian Misalignment (Evans et al., 2013) Misalignment L-11: 13% Flight: 21% Average Nightly Sleep L-11: 6.04h (aligned) 4.77h (misaligned) Flight: 6.33h (aligned) 5.34h (misaligned) Sleep Medication Usage L-11: 16% (aligned) 18% (misaligned) Flight: 11% (aligned) 28% (misaligned)

16 NEED TO KNOW #2 Light/dark = continuous interaction with humans Know your spectral power distribution (SPD) Blue wavelengths ( nm) key for significant nonphotic physiology

17 Fiat Lux Definitions/Background

18 Definitions/Background Light Light: Know Your Spectral Power Distribution (SPD) Be weary of color temperature (CCT) & Color Rendering Index (CRI) 4.54 billion years 137 (214) years 65 years 8 years

19 Definitions/Background

20 Choose Your Light Box

21 Choose Your Light Box A B C, D

22 Does it Work for SAD?

23 Does it Work for Alertness?

24 A Patient with Insomnia 53 YO F presents with 5-6 month history of sleeping <4 hours/night Difficulty with both sleep initiation and maintenance Reports Ambien (zolpidem) CR to be ineffective Prior to bed, attempts to relax on couch (next to light)...

25 A Patient with Insomnia

26 Bright (Blue) Light Naps Caffeine NEED TO KNOW #3

27 The Sleep-Deprived Pilot Countermeasures Light Bright, blue Caffeine

28 The Sleep-Deprived Pilot Countermeasures Light Bright, blue Caffeine SLEEP

29 The Sleep-Deprived Pilot Countermeasures Light Bright, blue Caffeine SLEEP

30 Reyner and Horne (1997) 30 minute drive 30 minute break 2 hour drive simulated motorway-type, dull, and tedious infrequent, mundane conversation

31 1 (1997) Reyner and Horne (1997) 30 minute drive 30 minute break 2 hour drive

32 NEED TO KNOW #1 Sleep deprivation and circadian misalignment decrease cognitive and physical performance Not all sleep deprivation and circadian misalignment is created equal There exist several, side-effect free, countermeasures

33 NEED TO KNOW #2 Light/dark = continuous interaction with humans Know your spectral power distribution (SPD) Blue wavelengths ( nm) key for significant nonphotic physiology

34 Bright (Blue) Light Naps Caffeine NEED TO KNOW #3

35 The Jet-Setting, Shift-Working Pilot Countermeasures Light, Darkness, Naps, Caffeine, Melatonin Phase Delay Phase Advance

36 The Jet-Setting, Shift-Working Pilot Countermeasures Light, Darkness, Naps, Caffeine, Melatonin Phase Delay Phase Advance

37 Pilot Astronaut Firefighter Police Officer Shift Worker Frequent Flyer Doctor Patient World... Save a...

38 Barger et al. Extended work duration and the risk of self-reported percutaneous injuries in interns [abstract only]. JAMA (2006): 296(9): Barger et al. Extended work shifts and the risk of motor vehicle crashes among interns [abstract only]. New England Journal of Medicine (2005): 352(2): Barger et al. High prevalence of sleep deficiency and hypnotic use among astronauts before and during Space Shuttle and International Space Station missions over the past decade. (Unpublished manuscript). Barger et al. Impact of extended-duration shifts on medical errors, adverse events, and attentional failures. PLoS Medicine (2006): 3(12):e487. Basner et al. Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing. Proceedings of the National Academy of Sciences of the United States of America(2013): 110(7): Blatter, Katharina and Christian Cajochen. Circaidan rhythms in cognitive performance: Methodological constraints, protocols, theoretical underpinnings. Physiology & Behavior (2007): 90(2-3): Czeisler et al. Stability, precision, and near-24-hour period of the human circadian pacemaker [abstract only]. Science (1999): 284(5423): Department of Health and Human Services Office of Inspector General. Adverse Events in Evans et al. Sleep Duration and Medication use Among Astronauts During Predicted Circadian Misalignment on Long Duration Missions Aboard the International Space Station. (Unpublished abstract). Hospitals: National Incidence Among Medicare Beneficiaries. Nov Mar < Google Image Search. Hatonen et al. Review of the Literature: Circadian Rhythms. 27 Mar < Hayashi et al. The alerting effects of caffeine, bright light and face washing after a short daytime nap. Clinical Neurophysiology (2003): 114: Ker et al. Caffeine for the prevention of injuries and errors in shift workers. The Cochrane Library, Issue 5, Chichester: Wiley. Monk et al. Circadian determinants of subjective alertness [abstract only, may be incorrect citation for chart]. Journal of Biological Rhythms (1989): 4(4): Philip et al. The Effects of Coffee and Napping on Nighttime Highway Driving: A Randomized Trial. Annals of Internal Medicine (2006): 144: Priest, Dana. War and Sleep; Why an $8 chaise longue became a prized accessory on the B-2 during the bombing of Yugoslavia. The Washington Post. 19 Nov Mar < Reyner, Louise and James Horne. Brief Report: Suppression of sleepiness in drivers: Combination of caffeine with a short nap. Psychophysiology (1997): 34: Unpublished NASA and Jefferson Light Research Lab research. Van Dongen et al. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep (2003): 26(2):

39 Thank You

40 BACKUP SLIDES

41 The Sleep-Deprived Pilot Narcolepsy 20 Residents Sleep Apnea Normal Insomnia 5 0

42 American Academy of Sleep Medicine The Sleep-Deprived Pilot NORMAL SLEEP = Paged MORNING ROUNDS ON CALL SLEEP

43 Definitions/Background

44 Methods Subjects diagnosed with Major Depression w/ Seasonal Pattern by SCID criteria and SIGH-SAD scores of 20. Each light unit had an array of 267 LEDs, measured 20 x 24 cm, and were viewed at a distance of 50 cm. ACGIH Hazard Analysis was conducted to assure safety of the light units. Random assignment, double-blind, to 468 nm or 654 nm used daily (45 m, between 0600 and 0800) for 3 weeks.

45 468 nm: 607 µw/cm2 55 % remitted 654 nm: 15 µw/cm2 31 % remitted Glickman, Byrne, Pineda, Hauck, Brainard: Biological Psychiatry (2006)

46 Thank You

47 Definitions/Background

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