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Improving Outcomes in Non–24-Hour Sleep-Wake Disorder Identifying Patients and Tailoring Therapy

Karl Doghramji, MD; Paul P. Doghramji, MD, FAAFP

This activity is jointly provided by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from Vanda Pharmaceuticals, Inc.

Faculty

Karl  Doghramji, MD
Professor of Psychiatry, Neurology, and Medicine
Medical Director, Jefferson Sleep Disorders Center
Program Director, Fellowship in Sleep Medicine
Thomas Jefferson University 
Philadelphia, Pennsylvania

Paul P.  Doghramji, MD, FAAFP
Family Physician
Collegeville Family Practice
Medical Director of Health Services
Ursinus University 
Collegeville, Pennsylvania

Educational Objectives

After completing this activity, the participant will be better able to:

  • Discuss the neurobiologic mechanisms that control circadian rhythms and the potential causes and multisystem consequences of disrupted daily cycles 
  • Identify patients with non-24-hour sleep-wake disorder based on common risk factors, presenting symptoms, a comprehensive sleep history, and published diagnostic criteria 
  • Tailor therapeutic regimens for patients with non–24-hour sleep-wake disorder, including appropriate combinations of nonpharmacologic and pharmacologic modalities

Target Audience

The educational design of this activity addresses the needs of primary care providers (PCPs), sleep specialists, and other clinicians involved in the identification and ongoing treatment of patients with non–24-hour sleep-wake disorder (non-24 disorder).

Statement of Need/Program Overview

Non-24 disorder is an intrinsic circadian rhythm disorder characterized by cyclic desynchronization between the patient’s endogenous physiologic rhythms and the earth’s 24-hour light/dark cycle.1,2 Although most affected individuals are totally blind and completely lack the daily entrainment signal provided by light, recent research has suggested that the disorder is more common than previously appreciated in partially blind patients, and—albeit still rare—in sighted teenagers and young adults.3,4 Delays or even complete failures in the diagnosis of non-24 disorder are all too common, in part because patients do not proactively discuss sleep problems with their clinicians.5,6 Time-constrained providers also may not specifically probe for the presence of the cardinal symptoms of excessive sleepiness and insomnia, even in high-risk cohorts.5,7 Clinicians are further challenged to individualize evidence-based treatment regimens, especially because the recently updated national practice parameters on managing intrinsic circadian rhythm disorders do not fully integrate the only agent that has been approved by the US Food and Drug Administration for the treatment of non-24 disorder.8,9 This online Point-of-Care 101 (POC101) program has been built around a 3D animation and lively discussions between 2 sleep medicine experts on the pathophysiologic basis of non-24 disorder, actionable diagnostic recommendations, nonpharmacologic treatment approaches, and the latest evidence for pharmacologic modalities.

  1. Zee PC, et al. Circadian rhythm abnormalities. Continuum (Minneap Minn). 2013;19(1 Sleep Disorders):132-147.
  2. American Academy of Sleep Medicine. International Classification of Sleep Disorders Diagnostic and Coding Manual, Second Edition (ICSD-3). 3rd ed. Westchester, IL: American Academy of Sleep Medicine; 2014.
  3. Hayakawa T, et al. Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: A study of 57 consecutively diagnosed cases. Sleep. 2005;28(8):945-952.
  4. Lockley SW, et al. Visual impairment and circadian rhythm disorders. Dialogues Clin Neurosci. 2007;9(3):301-314.
  5. Uchiyama M, Lockley SW. Non-24-hour sleep-wake syndrome in sighted and blind patients. Sleep Med Clin. 2015;10(4):495-516.
  6. National Sleep Foundation. 2009 Sleep in America Poll: Health and Safety. National Sleep Foundation. 2009:1-55.
  7. Sorscher AJ. How is your sleep: a neglected topic for health care screening. J Am Board Fam Med. 2008;21(2):141-148.
  8. Auger RR, et al. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2015;11(10):1199-1236.
  9. Lockley SW, et al. Tasimelteon for non-24-hour sleep–wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials. Lancet. 2015;386(10005):1754-1764..  

Physician Accreditation Statement

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas.  Global is accredited by the ACCME to provide continuing medical education for physicians.

Global Education Group designates this enduring activity for a maximum of 0.50 AMA PRA Category 1 Credit™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Global Contact Information

For information about the accreditation of this program, please contact Global at 303-395-1782 or inquire@globaleducationgroup.com

Instructions to Receive Credit

In order to receive credit for this activity, the participant must score 70% or better on the posttest and complete the program evaluation.

System Requirements

PC/MAC: Supports any web browser.

Fee Information & Refund/Cancellation Policy

There is no fee for this educational activity.

Disclosure of Conflicts of Interest

Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: 

Karl Doghramji, MD     Nothing to disclose.

Paul P. Doghramji, MD, FAAFP     Consultant (AstraZeneca, Merck & Co., Inc., Teva Pharmaceutical Industries Ltd.);
Speakers Bureau (Merck & Co., Inc., Takeda Pharmaceuticals U.S.A., Inc., Teva Pharmaceutical Industries Ltd.)

Amanda Glazar, PhD      Nothing to disclose
Andrea Funk      Nothing to disclose
Laura Gilsdorf      Nothing to disclose
Jim Kappler, PhD      Nothing to disclose

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global Education Group (Global) and Integritas Communications do not recommend the use of any agent outside of the labeled indications.  

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. 

Click "Begin Activity" to acknowledge that you have reviewed the preamble information for this activity.

Begin Activity

expiration 07/07/2017

type POC101


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SHOW COLUMNS FROM `activities`
1 0.001767 0.001767 0.001767 0.001767
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
5 0.001734 0.000347 0.000288 0.000508
SHOW COLUMNS FROM `events`
1 0.001462 0.001462 0.001462 0.001462
SHOW COLUMNS FROM `users`
1 0.001237 0.001237 0.001237 0.001237
SHOW COLUMNS FROM `view_log`
1 0.001211 0.001211 0.001211 0.001211
SHOW COLUMNS FROM `interactions`
1 0.001198 0.001198 0.001198 0.001198
SHOW CREATE TABLE `interactions`
1 0.001159 0.001159 0.001159 0.001159
SHOW COLUMNS FROM `resources`
1 0.001145 0.001145 0.001145 0.001145
select id, status from activities where FIND_IN_SET(:shortAddress, shortAddress)
2 0.001137 0.000569 0.000263 0.000874
SHOW COLUMNS FROM `questionnaires`
1 0.001026 0.001026 0.001026 0.001026
SHOW COLUMNS FROM `user_activitiesstatus`
1 0.001022 0.001022 0.001022 0.001022
SELECT * FROM `users` `t` WHERE session=:session LIMIT 1
2 0.000955 0.000477 0.000472 0.000483
SELECT `t`.`id` AS `t0_c0`, `t`.`group_id` AS `t0_c1`, `t`.`resource_id` AS `t0_c2`, `t`.`title` AS `t0_c3`, `t`.`type` AS `t0_c4`, `t`.`facultyNames` AS `t0_c5`, `t`.`shortDescription` AS `t0_c6`, `t`.`fullDescription` AS `t0_c7`, `t`.`creditAmount` AS `t0_c8`, `t`.`shortAddress` AS `t0_c9`, `t`.`creditType` AS `t0_c10`, `t`.`startDate` AS `t0_c11`, `t`.`finishDate` AS `t0_c12`, `t`.`sponsors` AS `t0_c13`, `t`.`status` AS `t0_c14`, `t`.`createDate` AS `t0_c15`, `t`.`image` AS `t0_c16`, `t`.`image_featured` AS `t0_c17`, `t`.`archived` AS `t0_c18`, `t`.`managers_list` AS `t0_c19`, `t`.`is_send_pp_email` AS `t0_c20`, `t`.`muvi_sync_date` AS `t0_c21`, `t`.`expert_questions` AS `t0_c22`, `interaction`.`id` AS `t1_c0`, `interaction`.`activity_id` AS `t1_c1`, `interaction`.`title` AS `t1_c2`, `interaction`.`link` AS `t1_c3`, `interaction`.`type` AS `t1_c4`, `interaction`.`status` AS `t1_c5`, `interaction`.`createDate` AS `t1_c6` FROM `activities` `t` LEFT OUTER JOIN `interactions` `interaction` ON (`interaction`.`activity_id`=`t`.`id`) WHERE (`t`.`id`=45)
1 0.000741 0.000741 0.000741 0.000741
SELECT `activity_id` AS `c`, COUNT(*) AS `s` FROM `user_activitiesstatus` `t` WHERE (user_id=:user AND isFinished=1) AND (`t`.`activity_id`=45) GROUP BY `activity_id`
1 0.000490 0.000490 0.000490 0.000490
SHOW CREATE TABLE `events`
1 0.000437 0.000437 0.000437 0.000437
SELECT * FROM `questionnaires` `t` WHERE t.activity_id=:id AND t.type=:type LIMIT 1
1 0.000425 0.000425 0.000425 0.000425
SHOW CREATE TABLE `activities`
1 0.000358 0.000358 0.000358 0.000358
SHOW CREATE TABLE `view_log`
1 0.000313 0.000313 0.000313 0.000313
SHOW CREATE TABLE `user_activitiesstatus`
1 0.000308 0.000308 0.000308 0.000308
SHOW CREATE TABLE `resources`
1 0.000308 0.000308 0.000308 0.000308
SHOW CREATE TABLE `users`
1 0.000306 0.000306 0.000306 0.000306
SHOW CREATE TABLE `questionnaires`
1 0.000296 0.000296 0.000296 0.000296
SELECT `resource`.`id` AS `t1_c0`, `resource`.`shortAddress` AS `t1_c1`, `resource`.`status` AS `t1_c2`, `resource`.`title` AS `t1_c3`, `resource`.`type` AS `t1_c4`, `resource`.`image` AS `t1_c5`, `resource`.`slides` AS `t1_c6`, `resource`.`linkedResources` AS `t1_c7`, `resource`.`reading` AS `t1_c8`, `resource`.`shortDescription` AS `t1_c9`, `resource`.`fullDescription` AS `t1_c10`, `resource`.`link` AS `t1_c11`, `resource`.`createDate` AS `t1_c12`, `resource`.`archived` AS `t1_c13` FROM `resources` `resource` WHERE (`resource`.`id`=:ypl0)
1 0.000295 0.000295 0.000295 0.000295
# Query Time (s)
0
select id, status from activities where FIND_IN_SET(:shortAddress, shortAddress)
0.000874
1
SHOW COLUMNS FROM `activities`
0.001767
2
SHOW CREATE TABLE `activities`
0.000358
3
SHOW COLUMNS FROM `users`
0.001237
4
SHOW CREATE TABLE `users`
0.000306
5
SELECT * FROM `users` `t` WHERE session=:session LIMIT 1
0.000472
6
INSERT INTO `users` (`role`, `sendEmails`, `sendSms`, `source`, `session`, `lastLogin`, `phone`, `createDate`) VALUES (:yp0, :yp1, :yp2, :yp3, :yp4, :yp5, :yp6, :yp7)
0.003856
7
SELECT * FROM `users` `t` WHERE session=:session LIMIT 1
0.000483
8
UPDATE `users` SET `lastLogin`=:yp0 WHERE `users`.`id`=2491934
0.002882
9
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
0.000508
10
SHOW COLUMNS FROM `events`
0.001462
11
SHOW CREATE TABLE `events`
0.000437
12
SELECT `event`.`id` AS `t1_c0`, `event`.`group_id` AS `t1_c1`, `event`.`shortAddress` AS `t1_c2`, `event`.`resource_id` AS `t1_c3`, `event`.`type` AS `t1_c4`, `event`.`addType` AS `t1_c5`, `event`.`title` AS `t1_c6`, `event`.`shortDescription` AS `t1_c7`, `event`.`facultyNames` AS `t1_c8`, `event`.`faculty` AS `t1_c9`, `event`.`calendarDate` AS `t1_c10`, `event`.`creditAmount` AS `t1_c11`, `event`.`creditType` AS `t1_c12`, `event`.`shortWhen` AS `t1_c13`, `event`.`fullWhen` AS `t1_c14`, `event`.`venue` AS `t1_c15`, `event`.`shortWhere` AS `t1_c16`, `event`.`fullWhere` AS `t1_c17`, `event`.`createDate` AS `t1_c18`, `event`.`status` AS `t1_c19`, `event`.`description` AS `t1_c20`, `event`.`image` AS `t1_c21`, `event`.`linkout` AS `t1_c22`, `event`.`registrationEnabled` AS `t1_c23`, `event`.`activity_id` AS `t1_c24`, `event`.`adobe_connect_sco` AS `t1_c25`, `event`.`adobe_connect_datetime` AS `t1_c26`, `event`.`users_limit` AS `t1_c27`, `event`.`adobe_connect_duration` AS `t1_c28`, `event`.`calendar_description` AS `t1_c29` FROM `events` `event` WHERE (`event`.`activity_id`=:ypl0)
0.001900
13
select id, status from activities where FIND_IN_SET(:shortAddress, shortAddress)
0.000263
14
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
0.000288
15
SELECT `event`.`id` AS `t1_c0`, `event`.`group_id` AS `t1_c1`, `event`.`shortAddress` AS `t1_c2`, `event`.`resource_id` AS `t1_c3`, `event`.`type` AS `t1_c4`, `event`.`addType` AS `t1_c5`, `event`.`title` AS `t1_c6`, `event`.`shortDescription` AS `t1_c7`, `event`.`facultyNames` AS `t1_c8`, `event`.`faculty` AS `t1_c9`, `event`.`calendarDate` AS `t1_c10`, `event`.`creditAmount` AS `t1_c11`, `event`.`creditType` AS `t1_c12`, `event`.`shortWhen` AS `t1_c13`, `event`.`fullWhen` AS `t1_c14`, `event`.`venue` AS `t1_c15`, `event`.`shortWhere` AS `t1_c16`, `event`.`fullWhere` AS `t1_c17`, `event`.`createDate` AS `t1_c18`, `event`.`status` AS `t1_c19`, `event`.`description` AS `t1_c20`, `event`.`image` AS `t1_c21`, `event`.`linkout` AS `t1_c22`, `event`.`registrationEnabled` AS `t1_c23`, `event`.`activity_id` AS `t1_c24`, `event`.`adobe_connect_sco` AS `t1_c25`, `event`.`adobe_connect_datetime` AS `t1_c26`, `event`.`users_limit` AS `t1_c27`, `event`.`adobe_connect_duration` AS `t1_c28`, `event`.`calendar_description` AS `t1_c29` FROM `events` `event` WHERE (`event`.`activity_id`=:ypl0)
0.000272
16
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
0.000303
17
UPDATE activities SET archived=1 WHERE finishDate<now();
0.005882
18
SHOW COLUMNS FROM `view_log`
0.001211
19
SHOW CREATE TABLE `view_log`
0.000313
20
INSERT INTO `view_log` (`source`, `unique_id`, `resource_id`, `type`) VALUES (:yp0, :yp1, :yp2, :yp3)
0.003258
21
SHOW COLUMNS FROM `user_activitiesstatus`
0.001022
22
SHOW CREATE TABLE `user_activitiesstatus`
0.000308
23
SHOW COLUMNS FROM `interactions`
0.001198
24
SHOW CREATE TABLE `interactions`
0.001159
25
SELECT `t`.`id` AS `t0_c0`, `t`.`group_id` AS `t0_c1`, `t`.`resource_id` AS `t0_c2`, `t`.`title` AS `t0_c3`, `t`.`type` AS `t0_c4`, `t`.`facultyNames` AS `t0_c5`, `t`.`shortDescription` AS `t0_c6`, `t`.`fullDescription` AS `t0_c7`, `t`.`creditAmount` AS `t0_c8`, `t`.`shortAddress` AS `t0_c9`, `t`.`creditType` AS `t0_c10`, `t`.`startDate` AS `t0_c11`, `t`.`finishDate` AS `t0_c12`, `t`.`sponsors` AS `t0_c13`, `t`.`status` AS `t0_c14`, `t`.`createDate` AS `t0_c15`, `t`.`image` AS `t0_c16`, `t`.`image_featured` AS `t0_c17`, `t`.`archived` AS `t0_c18`, `t`.`managers_list` AS `t0_c19`, `t`.`is_send_pp_email` AS `t0_c20`, `t`.`muvi_sync_date` AS `t0_c21`, `t`.`expert_questions` AS `t0_c22`, `interaction`.`id` AS `t1_c0`, `interaction`.`activity_id` AS `t1_c1`, `interaction`.`title` AS `t1_c2`, `interaction`.`link` AS `t1_c3`, `interaction`.`type` AS `t1_c4`, `interaction`.`status` AS `t1_c5`, `interaction`.`createDate` AS `t1_c6` FROM `activities` `t` LEFT OUTER JOIN `interactions` `interaction` ON (`interaction`.`activity_id`=`t`.`id`) WHERE (`t`.`id`=45)
0.000741
26
SELECT `activity_id` AS `c`, COUNT(*) AS `s` FROM `user_activitiesstatus` `t` WHERE (user_id=:user AND isFinished=1) AND (`t`.`activity_id`=45) GROUP BY `activity_id`
0.000490
27
SELECT `event`.`id` AS `t1_c0`, `event`.`group_id` AS `t1_c1`, `event`.`shortAddress` AS `t1_c2`, `event`.`resource_id` AS `t1_c3`, `event`.`type` AS `t1_c4`, `event`.`addType` AS `t1_c5`, `event`.`title` AS `t1_c6`, `event`.`shortDescription` AS `t1_c7`, `event`.`facultyNames` AS `t1_c8`, `event`.`faculty` AS `t1_c9`, `event`.`calendarDate` AS `t1_c10`, `event`.`creditAmount` AS `t1_c11`, `event`.`creditType` AS `t1_c12`, `event`.`shortWhen` AS `t1_c13`, `event`.`fullWhen` AS `t1_c14`, `event`.`venue` AS `t1_c15`, `event`.`shortWhere` AS `t1_c16`, `event`.`fullWhere` AS `t1_c17`, `event`.`createDate` AS `t1_c18`, `event`.`status` AS `t1_c19`, `event`.`description` AS `t1_c20`, `event`.`image` AS `t1_c21`, `event`.`linkout` AS `t1_c22`, `event`.`registrationEnabled` AS `t1_c23`, `event`.`activity_id` AS `t1_c24`, `event`.`adobe_connect_sco` AS `t1_c25`, `event`.`adobe_connect_datetime` AS `t1_c26`, `event`.`users_limit` AS `t1_c27`, `event`.`adobe_connect_duration` AS `t1_c28`, `event`.`calendar_description` AS `t1_c29` FROM `events` `event` WHERE (`event`.`activity_id`=:ypl0)
0.000282
28
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
0.000320
29
SELECT * FROM `activities` `t` WHERE `t`.`id`=45 LIMIT 1
0.000315
30
SHOW COLUMNS FROM `questionnaires`
0.001026
31
SHOW CREATE TABLE `questionnaires`
0.000296
32
SELECT * FROM `questionnaires` `t` WHERE t.activity_id=:id AND t.type=:type LIMIT 1
0.000425
33
SHOW COLUMNS FROM `resources`
0.001145
34
SHOW CREATE TABLE `resources`
0.000308
35
SELECT `resource`.`id` AS `t1_c0`, `resource`.`shortAddress` AS `t1_c1`, `resource`.`status` AS `t1_c2`, `resource`.`title` AS `t1_c3`, `resource`.`type` AS `t1_c4`, `resource`.`image` AS `t1_c5`, `resource`.`slides` AS `t1_c6`, `resource`.`linkedResources` AS `t1_c7`, `resource`.`reading` AS `t1_c8`, `resource`.`shortDescription` AS `t1_c9`, `resource`.`fullDescription` AS `t1_c10`, `resource`.`link` AS `t1_c11`, `resource`.`createDate` AS `t1_c12`, `resource`.`archived` AS `t1_c13` FROM `resources` `resource` WHERE (`resource`.`id`=:ypl0)
0.000295
Log Messages
Message (details) Level Category Time