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Study profiles sleep disruption in depression
Waking theta reduced in depression
BALTIMORE – Disruption of slow-wave activity may potentially explain the positive influence that sleep deprivation may have on major depressive disorder, according to results of a study presented at the annual meeting of the Associated Professional Sleep Societies.
Jennifer Goldschmied, PhD, of the University of Pennsylvania, Philadelphia, reported preliminary results of a study of slow-wave activity (SWA) disruption in 26 subjects – 12 healthy controls and 14 people diagnosed with major depressive disorder – that found a significant decrease of about 20% in waking theta activity, as measured with EEG, in the MDD group. In the 3-night sleep study, conducted at the University of Michigan, Ann Arbor, an adaptation night was followed by baseline and SWA disruption nights with EEGs performed each night. After the baseline night, patients also had a morning and afternoon EEG.
Across the baseline day, patients with depression showed “no modulation of theta activity whatsoever,” Dr. Goldschmied said. “And then we see, following slow-wave disruption, a significant decrease in theta activity,” whereas, healthy controls showed no change in waking theta following slow-wave disruption. “So what this means is that the presence of SWA may actually be facilitating the reduction of theta or sleep propensity during typical sleep in healthy individuals,” she added. In MDD patients, the decline in theta power following slow-wave disruption was from around 5.4 to 4.3.
Dr. Goldschmied noted that this finding somewhat supports what is known as the synaptic homeostasis hypothesis that University of Wisconsin researchers Giulio Tononi, MD, PhD, and Chiara Cirelli, MD, PhD, reported (Brain Res Bull. 2003;62:143-50). This hypothesis holds that SWA is a marker of synaptic strength and promotes the downscaling of synaptic strength during sleep. No method for measuring synaptic strength in humans exists, Dr. Goldschmied added, but waking theta can be considered a proxy for net synaptic strength across the cortex.
Dr. Goldschmied noted other research that has found SWA disruption improves mood (Psychiatry Res. 2015;228:715-8; J Psychiatr Res. 2011;45:1019-26), but the study she reported on found no role of decreased theta activity in that change. “To go even further,” she said, “we looked at the entire data set and found no relationship between the decrease in theta and any of the measures of sleep architecture – so there’s really no way to predict this decrease in our sample of people with depression.”
SWA plays a significant role in depression and merits more study, Dr. Goldschmied said. She noted that future research should examine the effects of SWA disruption in a larger sample, investigate theta findings with other proxy measures of synaptic strength such as brain-derived neurotrophic factor and transcranial magnetic stimulation, explore differences in SWA between sexes, and explore how SWA enhancement influences mood and theta activity.
Dr. Goldschmied reported having no financial relationships.
SOURCE: Goldschmied J et al. Sleep 2018, Abstract 0245.
Waking theta reduced in depression
Waking theta reduced in depression
BALTIMORE – Disruption of slow-wave activity may potentially explain the positive influence that sleep deprivation may have on major depressive disorder, according to results of a study presented at the annual meeting of the Associated Professional Sleep Societies.
Jennifer Goldschmied, PhD, of the University of Pennsylvania, Philadelphia, reported preliminary results of a study of slow-wave activity (SWA) disruption in 26 subjects – 12 healthy controls and 14 people diagnosed with major depressive disorder – that found a significant decrease of about 20% in waking theta activity, as measured with EEG, in the MDD group. In the 3-night sleep study, conducted at the University of Michigan, Ann Arbor, an adaptation night was followed by baseline and SWA disruption nights with EEGs performed each night. After the baseline night, patients also had a morning and afternoon EEG.
Across the baseline day, patients with depression showed “no modulation of theta activity whatsoever,” Dr. Goldschmied said. “And then we see, following slow-wave disruption, a significant decrease in theta activity,” whereas, healthy controls showed no change in waking theta following slow-wave disruption. “So what this means is that the presence of SWA may actually be facilitating the reduction of theta or sleep propensity during typical sleep in healthy individuals,” she added. In MDD patients, the decline in theta power following slow-wave disruption was from around 5.4 to 4.3.
Dr. Goldschmied noted that this finding somewhat supports what is known as the synaptic homeostasis hypothesis that University of Wisconsin researchers Giulio Tononi, MD, PhD, and Chiara Cirelli, MD, PhD, reported (Brain Res Bull. 2003;62:143-50). This hypothesis holds that SWA is a marker of synaptic strength and promotes the downscaling of synaptic strength during sleep. No method for measuring synaptic strength in humans exists, Dr. Goldschmied added, but waking theta can be considered a proxy for net synaptic strength across the cortex.
Dr. Goldschmied noted other research that has found SWA disruption improves mood (Psychiatry Res. 2015;228:715-8; J Psychiatr Res. 2011;45:1019-26), but the study she reported on found no role of decreased theta activity in that change. “To go even further,” she said, “we looked at the entire data set and found no relationship between the decrease in theta and any of the measures of sleep architecture – so there’s really no way to predict this decrease in our sample of people with depression.”
SWA plays a significant role in depression and merits more study, Dr. Goldschmied said. She noted that future research should examine the effects of SWA disruption in a larger sample, investigate theta findings with other proxy measures of synaptic strength such as brain-derived neurotrophic factor and transcranial magnetic stimulation, explore differences in SWA between sexes, and explore how SWA enhancement influences mood and theta activity.
Dr. Goldschmied reported having no financial relationships.
SOURCE: Goldschmied J et al. Sleep 2018, Abstract 0245.
BALTIMORE – Disruption of slow-wave activity may potentially explain the positive influence that sleep deprivation may have on major depressive disorder, according to results of a study presented at the annual meeting of the Associated Professional Sleep Societies.
Jennifer Goldschmied, PhD, of the University of Pennsylvania, Philadelphia, reported preliminary results of a study of slow-wave activity (SWA) disruption in 26 subjects – 12 healthy controls and 14 people diagnosed with major depressive disorder – that found a significant decrease of about 20% in waking theta activity, as measured with EEG, in the MDD group. In the 3-night sleep study, conducted at the University of Michigan, Ann Arbor, an adaptation night was followed by baseline and SWA disruption nights with EEGs performed each night. After the baseline night, patients also had a morning and afternoon EEG.
Across the baseline day, patients with depression showed “no modulation of theta activity whatsoever,” Dr. Goldschmied said. “And then we see, following slow-wave disruption, a significant decrease in theta activity,” whereas, healthy controls showed no change in waking theta following slow-wave disruption. “So what this means is that the presence of SWA may actually be facilitating the reduction of theta or sleep propensity during typical sleep in healthy individuals,” she added. In MDD patients, the decline in theta power following slow-wave disruption was from around 5.4 to 4.3.
Dr. Goldschmied noted that this finding somewhat supports what is known as the synaptic homeostasis hypothesis that University of Wisconsin researchers Giulio Tononi, MD, PhD, and Chiara Cirelli, MD, PhD, reported (Brain Res Bull. 2003;62:143-50). This hypothesis holds that SWA is a marker of synaptic strength and promotes the downscaling of synaptic strength during sleep. No method for measuring synaptic strength in humans exists, Dr. Goldschmied added, but waking theta can be considered a proxy for net synaptic strength across the cortex.
Dr. Goldschmied noted other research that has found SWA disruption improves mood (Psychiatry Res. 2015;228:715-8; J Psychiatr Res. 2011;45:1019-26), but the study she reported on found no role of decreased theta activity in that change. “To go even further,” she said, “we looked at the entire data set and found no relationship between the decrease in theta and any of the measures of sleep architecture – so there’s really no way to predict this decrease in our sample of people with depression.”
SWA plays a significant role in depression and merits more study, Dr. Goldschmied said. She noted that future research should examine the effects of SWA disruption in a larger sample, investigate theta findings with other proxy measures of synaptic strength such as brain-derived neurotrophic factor and transcranial magnetic stimulation, explore differences in SWA between sexes, and explore how SWA enhancement influences mood and theta activity.
Dr. Goldschmied reported having no financial relationships.
SOURCE: Goldschmied J et al. Sleep 2018, Abstract 0245.
REPORTING FROM SLEEP 2018
Key clinical point: Patients with major depression have reduced brain activity after sleep disruption.
Major finding: Morning theta activity was 20% lower following slow-wave disruption in patients with major depressive disorder than in healthy controls.
Data source: EEG measures of 14 individuals with major depressive disorder and 12 healthy controls in the evening before sleep and the morning following sleep after 1 night of baseline and 1 night of selective slow-wave disrupted sleep.
Disclosure: Dr. Goldschmied had no financial relationships to disclose.
Source: Goldschmied J et al. Sleep 2018, Abstract 0245.
Emerging CPAP options show sustained benefits
BALTIMORE – Emerging developments for the treatment of obstructive sleep apnea have shown promise in providing options beyond continuous-positive airway pressure, investigators reported at the annual meeting of the Associated Professional Sleep Societies. These developments include a single-use nasopharyngeal airway stent, upper-airway stimulation using a pacemaker-like device, a negative-pressure device that opens the airway, and an artificial intelligence approach that can predict outcomes of oral appliance therapy.
Nasopharyngeal airway stent
Clete A. Kushida, MD, of Stanford (Calif.) University reported on recent results of a trial of the nasopharyngeal airway stent (NAS) single-use disposable insert (Seven Dreamers Laboratories, Tokyo). This device consists of a flexible semi-rigid silicone rubber tube 120-145 mm in length and coated with a hydrophilic gel. The patient inserts the distal end of the tube into the nostril, and it positions itself within the nasopharynx and retropalatal oropharynx to open the airway. A clip attaches to the exterior septum to keep the device in place. The patient removes the NAS in the morning. The device is commercially available in Japan and some European countries.
Dr. Kushida reported on two posters that were presented at Sleep 2018. The first by the Osaka University Graduate School of Dentistry in Japan investigated the predictability of NAS efficacy in patients with a velopharynx that was narrower than the hypopharynx (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.554). The study showed that 11 responders had a narrow velopharynx while 18 nonresponders had a narrow hypopharynx. Response was defined as 50% or greater reduction of apnea-hypopnea index (AHI) from baseline. “The success rate of NAS for the patients with narrowing of the velopharynx is 83.3%,” Dr. Kushida said.
He also reported on a study he led of NAS in patients with obstructive sleep apnea and healthy controls (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.555). The trial was conducted at Stanford and Tokyo sleep medical centers, with healthy controls at the Tokyo site only. AHI improved in all three obstructive sleep apnea (OSA) groups, but most significantly in those with moderate (n = 23) and severe (n = 21) OSA: 7.2 (P = .0038) and 11.7 (P = .0069), respectively. In the Stanford cohort, 2 of 32 patients originally enrolled dropped out because they found the NAS uncomfortable; none dropped out of the Tokyo cohort.
“NAS can be effective in treatment of snoring and OSA, in particular those with moderate/severe OSA, with significant improvement in mean obstructive apnea index,” Dr. Kushida said. He also noted the device is more effective in patients with narrowing of the oropharynx/velopharynx rather than the hypopharynx.
Dr. Kushida reported he had a financial relationship with the Seven Dreamers Laboratories.
Continuous negative external pressure
Jerrold A. Kram, MD, reported on a device that employs continuous negative external pressure – known as cNEP – that uses a silicone collar covering the front of the throat and a pump that applies suction to keep the airway open from the outside. He cited a small 2015 study out of Japan that found the device was effective in keeping the pharyngeal airway open in nonobese women (J Appl Physiol. 2015;118:912-20). Another small U.S. study found cNEP reduces respiratory impairment during screening colonoscopy (Endoscopy. 2016;48:584-7). Sommetrics, which has patented the technology, is developing a version of the product for obstructive sleep apnea, Dr. Kram said. The company already has a Food and Drug Administration–approved product to treat apneas that people experience when under mild to moderate sedation, such as a colonoscopy. It is approved for sale in Canada, but not in the United States.
“It gives us another tool in the box,” Dr. Kram said. “It’s very small and portable, easy to take on an airplane with you, and it reduces the chance for claustrophobia” that comes with continuous-positive airway pressure (CPAP), said Dr. Kram. There are no tubes or masks and no humidifier to deal with.
Dr. Kram conducted a small study of 15 OSA patients using cNEP last year. Among nine excellent responders, the lowest AHI was 1.5 on average, from an average baseline of 43.9; among four partial responders, the lowest observed AHI averaged 11.75 (J Clin Sleep Med. 2017;13:1009-12).
The cNEP device is also the subject of a home study of patients with OSA in Canada, Dr. Kram said. Unpublished results indicate that 46% (27/59) of patients had an initial response rate to either -25 or -30 characteristic moment waveform (cmw) of negative airway pressure. For those who completed 3 weeks of treatment, the response rate was 64% (16/25). “Seventy-six percent of subjects felt their overall experience with cNEP was better than with CPAP,” Dr. Kram said.
However, studies have noted some minor issues with cNEP, Dr. Kram said. They include mild skin irritation, choking sensation if not properly placed, limited size availability, and absence of efficacy data. Dr. Kram said a U.S. pivotal trial is scheduled to start soon.
Dr. Kram disclosed he is a paid adviser for Sommetrics.
Oral appliance therapy
Oral appliance therapy (OAT) has been very effective in some patients and has been endorsed by the American Academy of Sleep Medicine since 2006, but it has been underutilized predominantly for two reasons, noted John Remmers, MD, because fitting the device requires a trial-and-error approach that can discourage patients; and the therapeutic success rate is 50%-60%.
To predict which patients are likely to succeed with OAT, Dr. Remmers and his colleagues at Zephyr Sleep Technologies have developed an artificial intelligence (AI) platform that uses a feedback-controlled mandibular positioner, a mouthpiece-like device that opens the airway during sleep. Dr. Remmers is chief medical officer and cofounder of Zephyr Sleep Technologies, based in Calgary, Alta.
While imaging has been used in awake patients to fit OAT devices, Dr. Remmers noted a number of shortcomings with this modality. “Sleep apnea results from an anatomic problem – i.e., structural encroachment on the pharyngeal airway, which is neurally compensated when the patient is awake,” he said. “Because of this, we need to do the test when the patient is asleep.”
The AI platform with feedback-controlled mandibular positioner uses temporary dental trays to create impressions for the mouthpiece the patient uses during sleep. The mouthpiece connects to a remote-controlled device that makes real-time adjustments in the mandibular position without disturbing the patient’s sleep. “The computer identifies respiratory events all night long, adjusting the position of the mandible,” he said in explaining the AI component of the device. “Just think of it as similar to autotitration with CPAP.”
Dr. Remmers reported results of a phase 2 study of the platform presented as a poster reporting on a study of 101 patients with OSA participants. The study reported sensitivity of 86% and specificity of 92% in predicting success with the feedback-controlled mandibular positioner, he said.
“The sensitivity and overall predictive accuracy of the AI-based approach was greater than an intuitive approach using a pretreatment, temporary appliance, indicating that feedback-controlled mandibular positioning test outperformed the intuitive approach,” he said. The device has been approved by Health Canada and is awaiting clearance in the United States.
Upper airway stimulation
Upper airway stimulation (UAS) is emerging as a new class of therapy, said Patrick J. Strollo Jr., MD, of the University of Pittsburgh. The therapy involves an impulse generator (IPG) similar to a pacemaker that is implanted in the left side of the chest and connected to a stimulation lead secured to the distal hypoglossal nerve in the neck. The UAS system also incorporates a sensing lead that is implanted between the intercostal muscles and attached to the IPG allowing for phasic stimulation of the genioglossal muscle. The patient uses a remote control to turn the device on at night and off in the morning.
Dr. Strollo was lead author of the Stimulation Therapy for Apnea Reduction (STAR) trial (N Engl J Med. 2014:370;139-49), a prospective multicenter trial with a randomized therapy withdrawal arm. In 126 participants, he said, the median AHI score declined 68% in 12 months, from 29.3 at baseline to 9 (P less than .0001).
He provided updated results that showed 80% of patients continued to use the device after 5 years (Otolaryngol Head Neck Surg. 2018; doi: 10.1177/0194599818762383). Median AHI at 5 years was 6.9, Dr. Strollo said, and median Epworth Sleepiness Scale scores declined from 11.6 at baseline to 6.9 at 5 years.
Another postapproval study of UAS, the ADHERE registry, has enrolled 348 patients at 10 centers with a goal of 2,500, Dr. Strollo said (Otolaryngol Head Neck Surg. 2018: doi: 10.1177/0194599818764896). Twelve-month study results have shown reductions in AHI and Epworth Sleepiness Scale scores comparable to previous reports. ADHERE also reported that 92% of patients were satisfied with UAS.
The latest innovation for UAS is the ability to download data from the implant at office visits so the physician can review patient adherence patterns, along with energy levels and settings for sensing and stimulation, Dr. Strollo said.
“Upper airway stimulation is an additional tool in the management of properly selected, at-risk apnea patients who do not accept or adhere to positive pressure therapy,” Dr. Strollo said. “The STAR trial has provided robust evidence that upper airway stimulation is safe and effective in participants with moderate to severe OSA, and the treatment effect is maintained beyond the 12-month endpoint.”
Dr. Strollo disclosed a financial relationship with Inspire Medical Systems, manufacturer of the UAS device.
BALTIMORE – Emerging developments for the treatment of obstructive sleep apnea have shown promise in providing options beyond continuous-positive airway pressure, investigators reported at the annual meeting of the Associated Professional Sleep Societies. These developments include a single-use nasopharyngeal airway stent, upper-airway stimulation using a pacemaker-like device, a negative-pressure device that opens the airway, and an artificial intelligence approach that can predict outcomes of oral appliance therapy.
Nasopharyngeal airway stent
Clete A. Kushida, MD, of Stanford (Calif.) University reported on recent results of a trial of the nasopharyngeal airway stent (NAS) single-use disposable insert (Seven Dreamers Laboratories, Tokyo). This device consists of a flexible semi-rigid silicone rubber tube 120-145 mm in length and coated with a hydrophilic gel. The patient inserts the distal end of the tube into the nostril, and it positions itself within the nasopharynx and retropalatal oropharynx to open the airway. A clip attaches to the exterior septum to keep the device in place. The patient removes the NAS in the morning. The device is commercially available in Japan and some European countries.
Dr. Kushida reported on two posters that were presented at Sleep 2018. The first by the Osaka University Graduate School of Dentistry in Japan investigated the predictability of NAS efficacy in patients with a velopharynx that was narrower than the hypopharynx (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.554). The study showed that 11 responders had a narrow velopharynx while 18 nonresponders had a narrow hypopharynx. Response was defined as 50% or greater reduction of apnea-hypopnea index (AHI) from baseline. “The success rate of NAS for the patients with narrowing of the velopharynx is 83.3%,” Dr. Kushida said.
He also reported on a study he led of NAS in patients with obstructive sleep apnea and healthy controls (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.555). The trial was conducted at Stanford and Tokyo sleep medical centers, with healthy controls at the Tokyo site only. AHI improved in all three obstructive sleep apnea (OSA) groups, but most significantly in those with moderate (n = 23) and severe (n = 21) OSA: 7.2 (P = .0038) and 11.7 (P = .0069), respectively. In the Stanford cohort, 2 of 32 patients originally enrolled dropped out because they found the NAS uncomfortable; none dropped out of the Tokyo cohort.
“NAS can be effective in treatment of snoring and OSA, in particular those with moderate/severe OSA, with significant improvement in mean obstructive apnea index,” Dr. Kushida said. He also noted the device is more effective in patients with narrowing of the oropharynx/velopharynx rather than the hypopharynx.
Dr. Kushida reported he had a financial relationship with the Seven Dreamers Laboratories.
Continuous negative external pressure
Jerrold A. Kram, MD, reported on a device that employs continuous negative external pressure – known as cNEP – that uses a silicone collar covering the front of the throat and a pump that applies suction to keep the airway open from the outside. He cited a small 2015 study out of Japan that found the device was effective in keeping the pharyngeal airway open in nonobese women (J Appl Physiol. 2015;118:912-20). Another small U.S. study found cNEP reduces respiratory impairment during screening colonoscopy (Endoscopy. 2016;48:584-7). Sommetrics, which has patented the technology, is developing a version of the product for obstructive sleep apnea, Dr. Kram said. The company already has a Food and Drug Administration–approved product to treat apneas that people experience when under mild to moderate sedation, such as a colonoscopy. It is approved for sale in Canada, but not in the United States.
“It gives us another tool in the box,” Dr. Kram said. “It’s very small and portable, easy to take on an airplane with you, and it reduces the chance for claustrophobia” that comes with continuous-positive airway pressure (CPAP), said Dr. Kram. There are no tubes or masks and no humidifier to deal with.
Dr. Kram conducted a small study of 15 OSA patients using cNEP last year. Among nine excellent responders, the lowest AHI was 1.5 on average, from an average baseline of 43.9; among four partial responders, the lowest observed AHI averaged 11.75 (J Clin Sleep Med. 2017;13:1009-12).
The cNEP device is also the subject of a home study of patients with OSA in Canada, Dr. Kram said. Unpublished results indicate that 46% (27/59) of patients had an initial response rate to either -25 or -30 characteristic moment waveform (cmw) of negative airway pressure. For those who completed 3 weeks of treatment, the response rate was 64% (16/25). “Seventy-six percent of subjects felt their overall experience with cNEP was better than with CPAP,” Dr. Kram said.
However, studies have noted some minor issues with cNEP, Dr. Kram said. They include mild skin irritation, choking sensation if not properly placed, limited size availability, and absence of efficacy data. Dr. Kram said a U.S. pivotal trial is scheduled to start soon.
Dr. Kram disclosed he is a paid adviser for Sommetrics.
Oral appliance therapy
Oral appliance therapy (OAT) has been very effective in some patients and has been endorsed by the American Academy of Sleep Medicine since 2006, but it has been underutilized predominantly for two reasons, noted John Remmers, MD, because fitting the device requires a trial-and-error approach that can discourage patients; and the therapeutic success rate is 50%-60%.
To predict which patients are likely to succeed with OAT, Dr. Remmers and his colleagues at Zephyr Sleep Technologies have developed an artificial intelligence (AI) platform that uses a feedback-controlled mandibular positioner, a mouthpiece-like device that opens the airway during sleep. Dr. Remmers is chief medical officer and cofounder of Zephyr Sleep Technologies, based in Calgary, Alta.
While imaging has been used in awake patients to fit OAT devices, Dr. Remmers noted a number of shortcomings with this modality. “Sleep apnea results from an anatomic problem – i.e., structural encroachment on the pharyngeal airway, which is neurally compensated when the patient is awake,” he said. “Because of this, we need to do the test when the patient is asleep.”
The AI platform with feedback-controlled mandibular positioner uses temporary dental trays to create impressions for the mouthpiece the patient uses during sleep. The mouthpiece connects to a remote-controlled device that makes real-time adjustments in the mandibular position without disturbing the patient’s sleep. “The computer identifies respiratory events all night long, adjusting the position of the mandible,” he said in explaining the AI component of the device. “Just think of it as similar to autotitration with CPAP.”
Dr. Remmers reported results of a phase 2 study of the platform presented as a poster reporting on a study of 101 patients with OSA participants. The study reported sensitivity of 86% and specificity of 92% in predicting success with the feedback-controlled mandibular positioner, he said.
“The sensitivity and overall predictive accuracy of the AI-based approach was greater than an intuitive approach using a pretreatment, temporary appliance, indicating that feedback-controlled mandibular positioning test outperformed the intuitive approach,” he said. The device has been approved by Health Canada and is awaiting clearance in the United States.
Upper airway stimulation
Upper airway stimulation (UAS) is emerging as a new class of therapy, said Patrick J. Strollo Jr., MD, of the University of Pittsburgh. The therapy involves an impulse generator (IPG) similar to a pacemaker that is implanted in the left side of the chest and connected to a stimulation lead secured to the distal hypoglossal nerve in the neck. The UAS system also incorporates a sensing lead that is implanted between the intercostal muscles and attached to the IPG allowing for phasic stimulation of the genioglossal muscle. The patient uses a remote control to turn the device on at night and off in the morning.
Dr. Strollo was lead author of the Stimulation Therapy for Apnea Reduction (STAR) trial (N Engl J Med. 2014:370;139-49), a prospective multicenter trial with a randomized therapy withdrawal arm. In 126 participants, he said, the median AHI score declined 68% in 12 months, from 29.3 at baseline to 9 (P less than .0001).
He provided updated results that showed 80% of patients continued to use the device after 5 years (Otolaryngol Head Neck Surg. 2018; doi: 10.1177/0194599818762383). Median AHI at 5 years was 6.9, Dr. Strollo said, and median Epworth Sleepiness Scale scores declined from 11.6 at baseline to 6.9 at 5 years.
Another postapproval study of UAS, the ADHERE registry, has enrolled 348 patients at 10 centers with a goal of 2,500, Dr. Strollo said (Otolaryngol Head Neck Surg. 2018: doi: 10.1177/0194599818764896). Twelve-month study results have shown reductions in AHI and Epworth Sleepiness Scale scores comparable to previous reports. ADHERE also reported that 92% of patients were satisfied with UAS.
The latest innovation for UAS is the ability to download data from the implant at office visits so the physician can review patient adherence patterns, along with energy levels and settings for sensing and stimulation, Dr. Strollo said.
“Upper airway stimulation is an additional tool in the management of properly selected, at-risk apnea patients who do not accept or adhere to positive pressure therapy,” Dr. Strollo said. “The STAR trial has provided robust evidence that upper airway stimulation is safe and effective in participants with moderate to severe OSA, and the treatment effect is maintained beyond the 12-month endpoint.”
Dr. Strollo disclosed a financial relationship with Inspire Medical Systems, manufacturer of the UAS device.
BALTIMORE – Emerging developments for the treatment of obstructive sleep apnea have shown promise in providing options beyond continuous-positive airway pressure, investigators reported at the annual meeting of the Associated Professional Sleep Societies. These developments include a single-use nasopharyngeal airway stent, upper-airway stimulation using a pacemaker-like device, a negative-pressure device that opens the airway, and an artificial intelligence approach that can predict outcomes of oral appliance therapy.
Nasopharyngeal airway stent
Clete A. Kushida, MD, of Stanford (Calif.) University reported on recent results of a trial of the nasopharyngeal airway stent (NAS) single-use disposable insert (Seven Dreamers Laboratories, Tokyo). This device consists of a flexible semi-rigid silicone rubber tube 120-145 mm in length and coated with a hydrophilic gel. The patient inserts the distal end of the tube into the nostril, and it positions itself within the nasopharynx and retropalatal oropharynx to open the airway. A clip attaches to the exterior septum to keep the device in place. The patient removes the NAS in the morning. The device is commercially available in Japan and some European countries.
Dr. Kushida reported on two posters that were presented at Sleep 2018. The first by the Osaka University Graduate School of Dentistry in Japan investigated the predictability of NAS efficacy in patients with a velopharynx that was narrower than the hypopharynx (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.554). The study showed that 11 responders had a narrow velopharynx while 18 nonresponders had a narrow hypopharynx. Response was defined as 50% or greater reduction of apnea-hypopnea index (AHI) from baseline. “The success rate of NAS for the patients with narrowing of the velopharynx is 83.3%,” Dr. Kushida said.
He also reported on a study he led of NAS in patients with obstructive sleep apnea and healthy controls (Sleep. 2018;41 (suppl 1):A207: doi.org/10.1093/sleep/zsy061.555). The trial was conducted at Stanford and Tokyo sleep medical centers, with healthy controls at the Tokyo site only. AHI improved in all three obstructive sleep apnea (OSA) groups, but most significantly in those with moderate (n = 23) and severe (n = 21) OSA: 7.2 (P = .0038) and 11.7 (P = .0069), respectively. In the Stanford cohort, 2 of 32 patients originally enrolled dropped out because they found the NAS uncomfortable; none dropped out of the Tokyo cohort.
“NAS can be effective in treatment of snoring and OSA, in particular those with moderate/severe OSA, with significant improvement in mean obstructive apnea index,” Dr. Kushida said. He also noted the device is more effective in patients with narrowing of the oropharynx/velopharynx rather than the hypopharynx.
Dr. Kushida reported he had a financial relationship with the Seven Dreamers Laboratories.
Continuous negative external pressure
Jerrold A. Kram, MD, reported on a device that employs continuous negative external pressure – known as cNEP – that uses a silicone collar covering the front of the throat and a pump that applies suction to keep the airway open from the outside. He cited a small 2015 study out of Japan that found the device was effective in keeping the pharyngeal airway open in nonobese women (J Appl Physiol. 2015;118:912-20). Another small U.S. study found cNEP reduces respiratory impairment during screening colonoscopy (Endoscopy. 2016;48:584-7). Sommetrics, which has patented the technology, is developing a version of the product for obstructive sleep apnea, Dr. Kram said. The company already has a Food and Drug Administration–approved product to treat apneas that people experience when under mild to moderate sedation, such as a colonoscopy. It is approved for sale in Canada, but not in the United States.
“It gives us another tool in the box,” Dr. Kram said. “It’s very small and portable, easy to take on an airplane with you, and it reduces the chance for claustrophobia” that comes with continuous-positive airway pressure (CPAP), said Dr. Kram. There are no tubes or masks and no humidifier to deal with.
Dr. Kram conducted a small study of 15 OSA patients using cNEP last year. Among nine excellent responders, the lowest AHI was 1.5 on average, from an average baseline of 43.9; among four partial responders, the lowest observed AHI averaged 11.75 (J Clin Sleep Med. 2017;13:1009-12).
The cNEP device is also the subject of a home study of patients with OSA in Canada, Dr. Kram said. Unpublished results indicate that 46% (27/59) of patients had an initial response rate to either -25 or -30 characteristic moment waveform (cmw) of negative airway pressure. For those who completed 3 weeks of treatment, the response rate was 64% (16/25). “Seventy-six percent of subjects felt their overall experience with cNEP was better than with CPAP,” Dr. Kram said.
However, studies have noted some minor issues with cNEP, Dr. Kram said. They include mild skin irritation, choking sensation if not properly placed, limited size availability, and absence of efficacy data. Dr. Kram said a U.S. pivotal trial is scheduled to start soon.
Dr. Kram disclosed he is a paid adviser for Sommetrics.
Oral appliance therapy
Oral appliance therapy (OAT) has been very effective in some patients and has been endorsed by the American Academy of Sleep Medicine since 2006, but it has been underutilized predominantly for two reasons, noted John Remmers, MD, because fitting the device requires a trial-and-error approach that can discourage patients; and the therapeutic success rate is 50%-60%.
To predict which patients are likely to succeed with OAT, Dr. Remmers and his colleagues at Zephyr Sleep Technologies have developed an artificial intelligence (AI) platform that uses a feedback-controlled mandibular positioner, a mouthpiece-like device that opens the airway during sleep. Dr. Remmers is chief medical officer and cofounder of Zephyr Sleep Technologies, based in Calgary, Alta.
While imaging has been used in awake patients to fit OAT devices, Dr. Remmers noted a number of shortcomings with this modality. “Sleep apnea results from an anatomic problem – i.e., structural encroachment on the pharyngeal airway, which is neurally compensated when the patient is awake,” he said. “Because of this, we need to do the test when the patient is asleep.”
The AI platform with feedback-controlled mandibular positioner uses temporary dental trays to create impressions for the mouthpiece the patient uses during sleep. The mouthpiece connects to a remote-controlled device that makes real-time adjustments in the mandibular position without disturbing the patient’s sleep. “The computer identifies respiratory events all night long, adjusting the position of the mandible,” he said in explaining the AI component of the device. “Just think of it as similar to autotitration with CPAP.”
Dr. Remmers reported results of a phase 2 study of the platform presented as a poster reporting on a study of 101 patients with OSA participants. The study reported sensitivity of 86% and specificity of 92% in predicting success with the feedback-controlled mandibular positioner, he said.
“The sensitivity and overall predictive accuracy of the AI-based approach was greater than an intuitive approach using a pretreatment, temporary appliance, indicating that feedback-controlled mandibular positioning test outperformed the intuitive approach,” he said. The device has been approved by Health Canada and is awaiting clearance in the United States.
Upper airway stimulation
Upper airway stimulation (UAS) is emerging as a new class of therapy, said Patrick J. Strollo Jr., MD, of the University of Pittsburgh. The therapy involves an impulse generator (IPG) similar to a pacemaker that is implanted in the left side of the chest and connected to a stimulation lead secured to the distal hypoglossal nerve in the neck. The UAS system also incorporates a sensing lead that is implanted between the intercostal muscles and attached to the IPG allowing for phasic stimulation of the genioglossal muscle. The patient uses a remote control to turn the device on at night and off in the morning.
Dr. Strollo was lead author of the Stimulation Therapy for Apnea Reduction (STAR) trial (N Engl J Med. 2014:370;139-49), a prospective multicenter trial with a randomized therapy withdrawal arm. In 126 participants, he said, the median AHI score declined 68% in 12 months, from 29.3 at baseline to 9 (P less than .0001).
He provided updated results that showed 80% of patients continued to use the device after 5 years (Otolaryngol Head Neck Surg. 2018; doi: 10.1177/0194599818762383). Median AHI at 5 years was 6.9, Dr. Strollo said, and median Epworth Sleepiness Scale scores declined from 11.6 at baseline to 6.9 at 5 years.
Another postapproval study of UAS, the ADHERE registry, has enrolled 348 patients at 10 centers with a goal of 2,500, Dr. Strollo said (Otolaryngol Head Neck Surg. 2018: doi: 10.1177/0194599818764896). Twelve-month study results have shown reductions in AHI and Epworth Sleepiness Scale scores comparable to previous reports. ADHERE also reported that 92% of patients were satisfied with UAS.
The latest innovation for UAS is the ability to download data from the implant at office visits so the physician can review patient adherence patterns, along with energy levels and settings for sensing and stimulation, Dr. Strollo said.
“Upper airway stimulation is an additional tool in the management of properly selected, at-risk apnea patients who do not accept or adhere to positive pressure therapy,” Dr. Strollo said. “The STAR trial has provided robust evidence that upper airway stimulation is safe and effective in participants with moderate to severe OSA, and the treatment effect is maintained beyond the 12-month endpoint.”
Dr. Strollo disclosed a financial relationship with Inspire Medical Systems, manufacturer of the UAS device.
REPORTING FROM SLEEP 2018
Key clinical point: Alternative treatments have shown sustained improvement in sleep apnea symptoms.
Major finding: The negative-pressure device improved oxygen flow in OSA to 64% vs. 25% for continuous-positive airway pressure.
Data source: Multiple abstracts presented at Sleep 2018 and published studies, including ADHERE study of 326 patients and a multicenter study of 430 patients using the upper airway stimulation device; a trial of 67 patients using the nasopharyngeal airway stent; and 101 patients in the artificial intelligence study.
Disclosures: Dr. Kushida disclosed a relationship with Seven Dreamers Laboratories. Dr. Kram is a paid adviser for Sommetrics. Dr. Remmers is founder of Zephyr Sleep Technologies. Dr. Strollo is an investigator in the STAR trial, supported by Inspire Medical Systems.
Phase 3 trial: Tasimelteon effective for jet lag disorder
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
REPORTING FROM SLEEP 2018
Key clinical point: The melatonin receptor agonist tasimelteon may improve sleep in jet lag.
Major finding: Total sleep times were 315.8 minutes for tasimelteon versus 230.3 for placebo.
Study details: JET8 randomized, double-blind, placebo-controlled, multicenter trial of 318 healthy subjects with induced jet lag disorder.
Disclosures: Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
CPAP and oxygen have different cardiac effects in OSA
BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.
“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.
The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.
On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.
The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.
Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.
The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.
Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.
SOURCE: George J et al. Sleep 2018, Abstract 0444.
BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.
“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.
The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.
On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.
The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.
Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.
The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.
Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.
SOURCE: George J et al. Sleep 2018, Abstract 0444.
BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.
“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.
The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.
On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.
The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.
Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.
The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.
Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.
SOURCE: George J et al. Sleep 2018, Abstract 0444.
REPORTING FROM SLEEP 2018
Key clinical point: CPAP and oxygen in sleep apnea have countering effects on ECG.
Major finding: CPAP conferred a 9% reduction in high-frequency power but a 4% increase in low-frequency power.
Study details: Evaluation of 203 participants in the multicenter, randomized controlled Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial.
Disclosures: Dr. George reported no financial relationships. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.
Source: George J et al. Sleep 2018, Abstract 0444.
OSA with worsening hypoxemia raises metabolic syndrome risk
BALTIMORE – An 8-year cohort study has found that patients with who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies
“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).
Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).
The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.
Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m2 vs. 23.8 kg/m2. Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.
Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.
The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).
“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.
A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”
Dr. Hirotsu reported having no conflicts of interest.
BALTIMORE – An 8-year cohort study has found that patients with who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies
“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).
Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).
The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.
Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m2 vs. 23.8 kg/m2. Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.
Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.
The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).
“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.
A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”
Dr. Hirotsu reported having no conflicts of interest.
BALTIMORE – An 8-year cohort study has found that patients with who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies
“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).
Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).
The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.
Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m2 vs. 23.8 kg/m2. Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.
Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.
The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).
“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.
A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”
Dr. Hirotsu reported having no conflicts of interest.
REPORTING FROM SLEEP 2018
Key clinical point: Obstructive sleep apnea may raise the risk of metabolic syndrome.
Major finding: Rates of moderate to severe OSA were 21.3% in the MetS group vs. 9% in the non-MetS group.
Study details: Observational, prospective cohort study of 476 patients with OSA who were free of MetS at enrollment in 2008.
Disclosures: Dr. Hirotsu and coauthors reported no financial relationships. The São Paulo Research Foundation, Association Research Incentive Fund and Brazilian National Council for Scientific and Technological Development funded the study.
Sleep problems may point to health disparity for black women
BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that according to a presentation at the annual meeting of the Associated Sleep Societies.
“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.
At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.
Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.
“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”
During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.
Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.
BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that according to a presentation at the annual meeting of the Associated Sleep Societies.
“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.
At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.
Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.
“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”
During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.
Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.
BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that according to a presentation at the annual meeting of the Associated Sleep Societies.
“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.
At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.
Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.
“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”
During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.
Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.
REPORTING FROM SLEEP 2018
Key clinical point: Black women are at greater risk for poor sleep help than white women.
Major finding: Beta coefficient for BMI and sleep health was –0.14 for black women and 0.1 for white women.
Study details: The SWAN sleep study, a multicenter, longitudinal, epidemiologic study of 265 midlife women.
Disclosures: Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.
Impact of marijuana on sleep not well understood
BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing , a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.
“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.
“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.
Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).
The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).
Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”
In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).
“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.
Dr. Sahni and her coauthors reported having no financial relationships to disclose.
BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing , a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.
“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.
“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.
Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).
The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).
Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”
In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).
“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.
Dr. Sahni and her coauthors reported having no financial relationships to disclose.
BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing , a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.
“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.
“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.
Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).
The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).
Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”
In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).
“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.
Dr. Sahni and her coauthors reported having no financial relationships to disclose.
EXPERT ANALYSIS FROM SLEEP 2018
Upping the game of surgical researchers
Many are submitted, but few are chosen.
Concerned about the quality of submitted research papers based on large surgical databases that are not accepted for publication, the editorial board of JAMA Surgery has taken the initiative by giving some pointers to would-be authors. The journal editors have published a 10-point checklist of dos and don’ts to address commonly seen problems with submitted manuscripts. In addition, JAMA Surgery collaborated with the Surgical Outcomes Club to commission a series of practical guides on the most widely used data sets in an effort to improve the quality of surgical database research. The Surgical Outcomes Club is a consortium of surgeons and scientists who work to advance health services and outcomes research in surgery that was launched in 2005 at the American College of Surgeons Clinical Congress.
The authors noted that, although JAMA Surgery receives hundreds of submissions of retrospective studies of large surgical databases each year, most of these studies have flaws in the data analysis or use a hypothesis that the data sets cannot address. Hence, the editors do not send most of them out for peer review. “Of those that are sent out for peer review, many are recommended to be rejected by expert peer reviewers as they find major methodological flaws in the use of these otherwise powerful data sets,” the team wrote.
“Research using data sets can be very powerful as the research can address questions and hypotheses using large populations of people. However, the research can have many weaknesses. First, the research is only as good as the data collection for each data set. Second, the investigator needs to be familiar with the types of research questions and hypotheses that can be addressed with each data set. Third, the statistical methodology used to analyze the data is also imperative,” said Dr. Kibbe in an interview.
The checklist begins with a recommendation that the researchers develop a clear, concise hypothesis using established criteria – either FINER (for feasible, interesting, novel, ethical, relevant) or PICO (patient, population, or problem; intervention, prognostic factor, or exposure; comparison or intervention; outcome); the checklist then goes on to include compliance with institutional review board and data use agreements and to emphasize the importance of a clear take-home message that addresses policy or clinical implications.
The series comprises 11 two-page articles that aim to serve as practical guides for using each of the most widely used surgical data sets, starting with the National Inpatient Sample and ending with the Society of Thoracic Surgeons data set. Each article includes a bulleted list of the data set’s attributes, an explanation of its limitations, a history of the data set, an explanation of how the data is collected and what is unique about the set’s features, and statistical considerations researchers should take into account when analyzing the data.
The series concludes with tips from the statistical editors of JAMA Surgery – Amy H. Kaji, MD, PhD, of Harbor–University of California Los Angeles Medical Center in Torrance; Alfred W. Rademaker, PhD, of Northwestern University, Chicago; and Terry Hyslop, PhD, of Duke University, Durham, N.C. – for performing statistical analysis of large data sets: “With bigger data, random signals may denote statistical significance, and precision may be incorrectly inferred because of narrow confidence intervals,” the statistical editors noted. “While many principles apply to all studies, the importance of these methodological issues is amplified in large, complex data sets.”
However, they noted that large data sets are prone to bias and measurement errors. “It is important to respect and acknowledge the limitations of the data,” the statistical team wrote. They also reprise the introductory editorial’s call for a clear hypothesis and take-home message. “The challenge with Big Data is that it requires a carefully thought-out research question and a transparent analytic strategy,” the statistical editors said.
And there are pitfalls. Dr. Bilimoria noted, “We shouldn’t let the database define our research. We should instead be asking interesting questions and then seeking out a database that fits best to answer the question.” He said one particular problem that comes up often for reviewers is trying to discern how researchers arrived at the population of interest in a study. “A lot of inclusion and exclusions criteria are applied, and unless [the reviewer] can see the decisions that were made in the process, some fairly important biases can be introduced unintentionally. We as reviewers would like to be able to follow that exclusion pathway.”
He said, “A problem we frequently see is that these databases change the variable definitions over time – in fact, change the variables over time. So if researchers aren’t checking to see if that variable was reported the same every year of the study and in the same way, they will get spurious results. Similarly, the number of hospitals reporting is important as well since hospitals come in and out of these data sets.”
In their introductory editorial, the JAMA Surgery team noted that the checklist, practical guides, and statistical tips are a three-pronged approach that authors should consult before submitting their manuscripts. “We hope that by following these simple guides, authors can benefit from the collective wisdom of so many colleagues who have successfully completed similar analyses in the past,” they wrote.
Dr. Bilimoria sees great strengths in database research, such as giving researchers a population-level view of how care is being delivered, insights into the outcomes of care, indications of the effects of policy decisions, and data on rare diseases and operations.
Big Data of all kinds will be increasingly available for researchers. Dr. Kibbe commented that, “In the future, having a comprehensive (not sampling) country- or worldwide electronic medical record that will allow for robust inclusion of all medical data at the individual as well as cohort level will greatly contribute to the era of personalized medicine. In my opinion, this would be a real-time inclusive medical database that would allow for individual as well as population-based prospective studies.”
Dr. Haider receives support from the Henry M. Jackson Foundation of the Department of Defense, the Orthopaedic Research and Education Foundation, and the National Institutes of Health, and nonfinancial research support the Centers for Medicare and Medicaid Services Office of Minority Health. Dr. Bilimoria was the president of the Surgical Outcomes Club from 2016 to 2017.
Many are submitted, but few are chosen.
Concerned about the quality of submitted research papers based on large surgical databases that are not accepted for publication, the editorial board of JAMA Surgery has taken the initiative by giving some pointers to would-be authors. The journal editors have published a 10-point checklist of dos and don’ts to address commonly seen problems with submitted manuscripts. In addition, JAMA Surgery collaborated with the Surgical Outcomes Club to commission a series of practical guides on the most widely used data sets in an effort to improve the quality of surgical database research. The Surgical Outcomes Club is a consortium of surgeons and scientists who work to advance health services and outcomes research in surgery that was launched in 2005 at the American College of Surgeons Clinical Congress.
The authors noted that, although JAMA Surgery receives hundreds of submissions of retrospective studies of large surgical databases each year, most of these studies have flaws in the data analysis or use a hypothesis that the data sets cannot address. Hence, the editors do not send most of them out for peer review. “Of those that are sent out for peer review, many are recommended to be rejected by expert peer reviewers as they find major methodological flaws in the use of these otherwise powerful data sets,” the team wrote.
“Research using data sets can be very powerful as the research can address questions and hypotheses using large populations of people. However, the research can have many weaknesses. First, the research is only as good as the data collection for each data set. Second, the investigator needs to be familiar with the types of research questions and hypotheses that can be addressed with each data set. Third, the statistical methodology used to analyze the data is also imperative,” said Dr. Kibbe in an interview.
The checklist begins with a recommendation that the researchers develop a clear, concise hypothesis using established criteria – either FINER (for feasible, interesting, novel, ethical, relevant) or PICO (patient, population, or problem; intervention, prognostic factor, or exposure; comparison or intervention; outcome); the checklist then goes on to include compliance with institutional review board and data use agreements and to emphasize the importance of a clear take-home message that addresses policy or clinical implications.
The series comprises 11 two-page articles that aim to serve as practical guides for using each of the most widely used surgical data sets, starting with the National Inpatient Sample and ending with the Society of Thoracic Surgeons data set. Each article includes a bulleted list of the data set’s attributes, an explanation of its limitations, a history of the data set, an explanation of how the data is collected and what is unique about the set’s features, and statistical considerations researchers should take into account when analyzing the data.
The series concludes with tips from the statistical editors of JAMA Surgery – Amy H. Kaji, MD, PhD, of Harbor–University of California Los Angeles Medical Center in Torrance; Alfred W. Rademaker, PhD, of Northwestern University, Chicago; and Terry Hyslop, PhD, of Duke University, Durham, N.C. – for performing statistical analysis of large data sets: “With bigger data, random signals may denote statistical significance, and precision may be incorrectly inferred because of narrow confidence intervals,” the statistical editors noted. “While many principles apply to all studies, the importance of these methodological issues is amplified in large, complex data sets.”
However, they noted that large data sets are prone to bias and measurement errors. “It is important to respect and acknowledge the limitations of the data,” the statistical team wrote. They also reprise the introductory editorial’s call for a clear hypothesis and take-home message. “The challenge with Big Data is that it requires a carefully thought-out research question and a transparent analytic strategy,” the statistical editors said.
And there are pitfalls. Dr. Bilimoria noted, “We shouldn’t let the database define our research. We should instead be asking interesting questions and then seeking out a database that fits best to answer the question.” He said one particular problem that comes up often for reviewers is trying to discern how researchers arrived at the population of interest in a study. “A lot of inclusion and exclusions criteria are applied, and unless [the reviewer] can see the decisions that were made in the process, some fairly important biases can be introduced unintentionally. We as reviewers would like to be able to follow that exclusion pathway.”
He said, “A problem we frequently see is that these databases change the variable definitions over time – in fact, change the variables over time. So if researchers aren’t checking to see if that variable was reported the same every year of the study and in the same way, they will get spurious results. Similarly, the number of hospitals reporting is important as well since hospitals come in and out of these data sets.”
In their introductory editorial, the JAMA Surgery team noted that the checklist, practical guides, and statistical tips are a three-pronged approach that authors should consult before submitting their manuscripts. “We hope that by following these simple guides, authors can benefit from the collective wisdom of so many colleagues who have successfully completed similar analyses in the past,” they wrote.
Dr. Bilimoria sees great strengths in database research, such as giving researchers a population-level view of how care is being delivered, insights into the outcomes of care, indications of the effects of policy decisions, and data on rare diseases and operations.
Big Data of all kinds will be increasingly available for researchers. Dr. Kibbe commented that, “In the future, having a comprehensive (not sampling) country- or worldwide electronic medical record that will allow for robust inclusion of all medical data at the individual as well as cohort level will greatly contribute to the era of personalized medicine. In my opinion, this would be a real-time inclusive medical database that would allow for individual as well as population-based prospective studies.”
Dr. Haider receives support from the Henry M. Jackson Foundation of the Department of Defense, the Orthopaedic Research and Education Foundation, and the National Institutes of Health, and nonfinancial research support the Centers for Medicare and Medicaid Services Office of Minority Health. Dr. Bilimoria was the president of the Surgical Outcomes Club from 2016 to 2017.
Many are submitted, but few are chosen.
Concerned about the quality of submitted research papers based on large surgical databases that are not accepted for publication, the editorial board of JAMA Surgery has taken the initiative by giving some pointers to would-be authors. The journal editors have published a 10-point checklist of dos and don’ts to address commonly seen problems with submitted manuscripts. In addition, JAMA Surgery collaborated with the Surgical Outcomes Club to commission a series of practical guides on the most widely used data sets in an effort to improve the quality of surgical database research. The Surgical Outcomes Club is a consortium of surgeons and scientists who work to advance health services and outcomes research in surgery that was launched in 2005 at the American College of Surgeons Clinical Congress.
The authors noted that, although JAMA Surgery receives hundreds of submissions of retrospective studies of large surgical databases each year, most of these studies have flaws in the data analysis or use a hypothesis that the data sets cannot address. Hence, the editors do not send most of them out for peer review. “Of those that are sent out for peer review, many are recommended to be rejected by expert peer reviewers as they find major methodological flaws in the use of these otherwise powerful data sets,” the team wrote.
“Research using data sets can be very powerful as the research can address questions and hypotheses using large populations of people. However, the research can have many weaknesses. First, the research is only as good as the data collection for each data set. Second, the investigator needs to be familiar with the types of research questions and hypotheses that can be addressed with each data set. Third, the statistical methodology used to analyze the data is also imperative,” said Dr. Kibbe in an interview.
The checklist begins with a recommendation that the researchers develop a clear, concise hypothesis using established criteria – either FINER (for feasible, interesting, novel, ethical, relevant) or PICO (patient, population, or problem; intervention, prognostic factor, or exposure; comparison or intervention; outcome); the checklist then goes on to include compliance with institutional review board and data use agreements and to emphasize the importance of a clear take-home message that addresses policy or clinical implications.
The series comprises 11 two-page articles that aim to serve as practical guides for using each of the most widely used surgical data sets, starting with the National Inpatient Sample and ending with the Society of Thoracic Surgeons data set. Each article includes a bulleted list of the data set’s attributes, an explanation of its limitations, a history of the data set, an explanation of how the data is collected and what is unique about the set’s features, and statistical considerations researchers should take into account when analyzing the data.
The series concludes with tips from the statistical editors of JAMA Surgery – Amy H. Kaji, MD, PhD, of Harbor–University of California Los Angeles Medical Center in Torrance; Alfred W. Rademaker, PhD, of Northwestern University, Chicago; and Terry Hyslop, PhD, of Duke University, Durham, N.C. – for performing statistical analysis of large data sets: “With bigger data, random signals may denote statistical significance, and precision may be incorrectly inferred because of narrow confidence intervals,” the statistical editors noted. “While many principles apply to all studies, the importance of these methodological issues is amplified in large, complex data sets.”
However, they noted that large data sets are prone to bias and measurement errors. “It is important to respect and acknowledge the limitations of the data,” the statistical team wrote. They also reprise the introductory editorial’s call for a clear hypothesis and take-home message. “The challenge with Big Data is that it requires a carefully thought-out research question and a transparent analytic strategy,” the statistical editors said.
And there are pitfalls. Dr. Bilimoria noted, “We shouldn’t let the database define our research. We should instead be asking interesting questions and then seeking out a database that fits best to answer the question.” He said one particular problem that comes up often for reviewers is trying to discern how researchers arrived at the population of interest in a study. “A lot of inclusion and exclusions criteria are applied, and unless [the reviewer] can see the decisions that were made in the process, some fairly important biases can be introduced unintentionally. We as reviewers would like to be able to follow that exclusion pathway.”
He said, “A problem we frequently see is that these databases change the variable definitions over time – in fact, change the variables over time. So if researchers aren’t checking to see if that variable was reported the same every year of the study and in the same way, they will get spurious results. Similarly, the number of hospitals reporting is important as well since hospitals come in and out of these data sets.”
In their introductory editorial, the JAMA Surgery team noted that the checklist, practical guides, and statistical tips are a three-pronged approach that authors should consult before submitting their manuscripts. “We hope that by following these simple guides, authors can benefit from the collective wisdom of so many colleagues who have successfully completed similar analyses in the past,” they wrote.
Dr. Bilimoria sees great strengths in database research, such as giving researchers a population-level view of how care is being delivered, insights into the outcomes of care, indications of the effects of policy decisions, and data on rare diseases and operations.
Big Data of all kinds will be increasingly available for researchers. Dr. Kibbe commented that, “In the future, having a comprehensive (not sampling) country- or worldwide electronic medical record that will allow for robust inclusion of all medical data at the individual as well as cohort level will greatly contribute to the era of personalized medicine. In my opinion, this would be a real-time inclusive medical database that would allow for individual as well as population-based prospective studies.”
Dr. Haider receives support from the Henry M. Jackson Foundation of the Department of Defense, the Orthopaedic Research and Education Foundation, and the National Institutes of Health, and nonfinancial research support the Centers for Medicare and Medicaid Services Office of Minority Health. Dr. Bilimoria was the president of the Surgical Outcomes Club from 2016 to 2017.
Enhanced recovery led to fewer complications for major oncologic procedures
CHICAGO – Use of an enhanced recovery protocol for oncology patients has been shown to improve outcomes in colorectal surgery but has been largely unproven in other types of major oncology operations. That prompted researchers at the University of Texas MD Anderson Cancer Center in Houston to investigate They found that the enhanced recovery protocol led to a reduction in complication rates and a decrease in hospital stay with no increase in readmissions, according to an analysis of more than 3,000 oncologic operations presented at the Society of Surgical Oncology Annual Cancer Symposium here.
“Patients treated with enhanced recovery did better,” Rebecca Marcus, MD, said in reporting the results. “There were decreased rates of perioperative transfusions, decreased rates of surgical site infections, decreased rates of complications, including severe complications such as wound dehiscence, pneumonia, renal failure, and unintended returns to the operating room.” She noted that the shorter hospital stays – 4 days for patients on the enhanced recovery protocol versus 5 days for those on the traditional postoperative protocol – did not result in increased readmissions.
The study reviewed 3,256 operations performed during 2011-2016 in the MD Anderson institutional American College of Surgeons National Surgical Quality Improvement Program database. The operations were colorectal (20.4%), gynecologic (19.5%), hepatobiliary (8.9%), thoracic (41.9%) and urologic (9.3%). Most employed the traditional postoperative protocol (53.4%). Colorectal and thoracic/vascular surgery were early adopters of the enhanced recovery protocol at MD Anderson.
Dr. Marcus noted that the overall complication rates were 21.9% for those treated with enhanced recovery–protocol versus 33.9% for those treated with traditional postoperative protocol (P less than .0001). The group treated with enhanced recovery protocol also had lower rates of severe complications: 8.7% vs. 11.7% (P =.0048). The study also noted a trend toward reduced National Surgical Quality Improvement Program 30-day mortality with the enhanced recover protocol (0.4% vs. 0.86%; P = .097). Readmission rates were similar between the two groups: 8.3% for enhanced recovery protocol versus 8.9% for traditional postoperative protocol.
The researchers performed a subanalysis of high-magnitude cases that had a relative value unit of 30 or more and involved operations of greater complexity, which constituted 38% of the study population. “In this group, we still saw the benefit of having treatment with an enhanced recovery protocol with decreased rates of preoperative transfusions, complications, and shorter length of stay without any recent readmission,” Dr. Marcus said. Complication rates in the high-magnitude group were 19% for the enhanced recovery protocol versus 26% for the traditional postoperative protocol in colorectal cases, 21% vs. 40% in gynecology, and 19% vs. 28% in thoracic/vascular.
“The beneficial impact of enhanced recovery appears to be maintained across all specialties and to be independent of case magnitude,” Dr. Marcus said.
She said future research of enhanced recovery in surgical oncology should focus on more long-term outcomes, “such as oncologic benefits of these protocols, especially given the known detrimental effect of the delayed return to adjuvant therapy for this patient population.”
Dr. Marcus and her coauthors reported having no financial disclosures.
SOURCE: Marcus RK et al. SSO 2018, Abstract 21.
CHICAGO – Use of an enhanced recovery protocol for oncology patients has been shown to improve outcomes in colorectal surgery but has been largely unproven in other types of major oncology operations. That prompted researchers at the University of Texas MD Anderson Cancer Center in Houston to investigate They found that the enhanced recovery protocol led to a reduction in complication rates and a decrease in hospital stay with no increase in readmissions, according to an analysis of more than 3,000 oncologic operations presented at the Society of Surgical Oncology Annual Cancer Symposium here.
“Patients treated with enhanced recovery did better,” Rebecca Marcus, MD, said in reporting the results. “There were decreased rates of perioperative transfusions, decreased rates of surgical site infections, decreased rates of complications, including severe complications such as wound dehiscence, pneumonia, renal failure, and unintended returns to the operating room.” She noted that the shorter hospital stays – 4 days for patients on the enhanced recovery protocol versus 5 days for those on the traditional postoperative protocol – did not result in increased readmissions.
The study reviewed 3,256 operations performed during 2011-2016 in the MD Anderson institutional American College of Surgeons National Surgical Quality Improvement Program database. The operations were colorectal (20.4%), gynecologic (19.5%), hepatobiliary (8.9%), thoracic (41.9%) and urologic (9.3%). Most employed the traditional postoperative protocol (53.4%). Colorectal and thoracic/vascular surgery were early adopters of the enhanced recovery protocol at MD Anderson.
Dr. Marcus noted that the overall complication rates were 21.9% for those treated with enhanced recovery–protocol versus 33.9% for those treated with traditional postoperative protocol (P less than .0001). The group treated with enhanced recovery protocol also had lower rates of severe complications: 8.7% vs. 11.7% (P =.0048). The study also noted a trend toward reduced National Surgical Quality Improvement Program 30-day mortality with the enhanced recover protocol (0.4% vs. 0.86%; P = .097). Readmission rates were similar between the two groups: 8.3% for enhanced recovery protocol versus 8.9% for traditional postoperative protocol.
The researchers performed a subanalysis of high-magnitude cases that had a relative value unit of 30 or more and involved operations of greater complexity, which constituted 38% of the study population. “In this group, we still saw the benefit of having treatment with an enhanced recovery protocol with decreased rates of preoperative transfusions, complications, and shorter length of stay without any recent readmission,” Dr. Marcus said. Complication rates in the high-magnitude group were 19% for the enhanced recovery protocol versus 26% for the traditional postoperative protocol in colorectal cases, 21% vs. 40% in gynecology, and 19% vs. 28% in thoracic/vascular.
“The beneficial impact of enhanced recovery appears to be maintained across all specialties and to be independent of case magnitude,” Dr. Marcus said.
She said future research of enhanced recovery in surgical oncology should focus on more long-term outcomes, “such as oncologic benefits of these protocols, especially given the known detrimental effect of the delayed return to adjuvant therapy for this patient population.”
Dr. Marcus and her coauthors reported having no financial disclosures.
SOURCE: Marcus RK et al. SSO 2018, Abstract 21.
CHICAGO – Use of an enhanced recovery protocol for oncology patients has been shown to improve outcomes in colorectal surgery but has been largely unproven in other types of major oncology operations. That prompted researchers at the University of Texas MD Anderson Cancer Center in Houston to investigate They found that the enhanced recovery protocol led to a reduction in complication rates and a decrease in hospital stay with no increase in readmissions, according to an analysis of more than 3,000 oncologic operations presented at the Society of Surgical Oncology Annual Cancer Symposium here.
“Patients treated with enhanced recovery did better,” Rebecca Marcus, MD, said in reporting the results. “There were decreased rates of perioperative transfusions, decreased rates of surgical site infections, decreased rates of complications, including severe complications such as wound dehiscence, pneumonia, renal failure, and unintended returns to the operating room.” She noted that the shorter hospital stays – 4 days for patients on the enhanced recovery protocol versus 5 days for those on the traditional postoperative protocol – did not result in increased readmissions.
The study reviewed 3,256 operations performed during 2011-2016 in the MD Anderson institutional American College of Surgeons National Surgical Quality Improvement Program database. The operations were colorectal (20.4%), gynecologic (19.5%), hepatobiliary (8.9%), thoracic (41.9%) and urologic (9.3%). Most employed the traditional postoperative protocol (53.4%). Colorectal and thoracic/vascular surgery were early adopters of the enhanced recovery protocol at MD Anderson.
Dr. Marcus noted that the overall complication rates were 21.9% for those treated with enhanced recovery–protocol versus 33.9% for those treated with traditional postoperative protocol (P less than .0001). The group treated with enhanced recovery protocol also had lower rates of severe complications: 8.7% vs. 11.7% (P =.0048). The study also noted a trend toward reduced National Surgical Quality Improvement Program 30-day mortality with the enhanced recover protocol (0.4% vs. 0.86%; P = .097). Readmission rates were similar between the two groups: 8.3% for enhanced recovery protocol versus 8.9% for traditional postoperative protocol.
The researchers performed a subanalysis of high-magnitude cases that had a relative value unit of 30 or more and involved operations of greater complexity, which constituted 38% of the study population. “In this group, we still saw the benefit of having treatment with an enhanced recovery protocol with decreased rates of preoperative transfusions, complications, and shorter length of stay without any recent readmission,” Dr. Marcus said. Complication rates in the high-magnitude group were 19% for the enhanced recovery protocol versus 26% for the traditional postoperative protocol in colorectal cases, 21% vs. 40% in gynecology, and 19% vs. 28% in thoracic/vascular.
“The beneficial impact of enhanced recovery appears to be maintained across all specialties and to be independent of case magnitude,” Dr. Marcus said.
She said future research of enhanced recovery in surgical oncology should focus on more long-term outcomes, “such as oncologic benefits of these protocols, especially given the known detrimental effect of the delayed return to adjuvant therapy for this patient population.”
Dr. Marcus and her coauthors reported having no financial disclosures.
SOURCE: Marcus RK et al. SSO 2018, Abstract 21.
REPORTING FROM SSO 2018
Key clinical point: Enhanced recovery protocol implementation is feasible in major oncologic surgery.
Major finding: Complication rates were 21.9% for enhanced recovery protocol versus 33.9% for traditional postoperative protocol.
Study details: Analysis of 3,256 oncology operations in an institutional ACS NSQIP database performed from 2011 to 2016.
Disclosures: Dr. Marcus and her coauthors reported having no financial disclosures.
Source: Marcus RK et al. SSO 2018, Abstract 21
Gene strong predictor of metastasis in melanoma
CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.
The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.
The rationale for analyzing the 79 genes implicated in cancer only rather than the entire array of 22,000 genes was to reduce the odds of a high false-discovery rate from 5% to 0.007%. “This is what strengthens our findings in a cohort of 37 patients,” Dr. Erdrich said.
The study analyzed pathological characteristics of the metastatic and nonmetastatic groups. Most characteristics were similar between the two groups, including location of the primary tumor in the trunk and extremities of 67% and 71%, respectively, and age of 60 years and older. The analysis noted two deviations: primary tumor size was thicker in the metastatic group (2.1 mm vs. 1.05 mm; P = .6), although Dr. Erdrich noted this was “not significantly different”; and a higher rate of ulceration in the metastatic group (50% vs. 13%; P = .05).
The genes CXCL1 and CXCL2 are both chemokines involved in growth and inflammation. “CXCL1 expression was 2.51 times greater in the metastatic group,” Dr. Erdrich said (P less than .001). Overexpression in the other three genes of interest was: CXCL2, 1.68 times greater (P less than .01); CD276, which is involved in T-cell immunity, 1.16 times greater (P = .04); and C-CBL, which is a photo-oncogene involved in the ubiquitin pathway, 1.15 times greater (P = .01). “The overexpression of all four of these was statistically significant,” she said.
Univariate analysis found ulceration of the primary along with overexpression of
the four genes to be significant predictors of metastasis. “However, in our multivariate model, three of the genes dropped out but CXCL1 remained robust,” she said.
Dr. Erdrich noted that CXCL1 is a cytokine located on chromosome 4, is secreted by macrophages, exerts its signal through CXCR2, and is one of five cytokines upregulated in lesions that respond to immunotherapy (Br J Dermatol. 2016;175:966-78).
CXCL1 compares favorably with S100, the existing blood-based biomarker for predicting recurrence in high-risk melanoma, as a predictor of metastases, Dr. Erdrich said, with an area under the curve of 0.80 versus 0.66; sensitivity of 67% versus 77%; specificity of 97% versus 61%; positive predictive value of 80% versus 40%; and negative predictive value of 94% versus 88% (Anticancer Res. 1999;19:2685-90; Cancer. 2003;97:1737-45).
The study also looked at overall survival in patients with low and high expression of CXCL1. “The patients with high expression had 5-year survival of only 50% compared to those of low expression, whose 5-year survival was 97%,” Dr. Erdrich said.
Dr. Erdrich and her coauthors reported having no financial relationships.
SOURCE: Erdrich J et al. SSO 2018, Abstract 82.
CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.
The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.
The rationale for analyzing the 79 genes implicated in cancer only rather than the entire array of 22,000 genes was to reduce the odds of a high false-discovery rate from 5% to 0.007%. “This is what strengthens our findings in a cohort of 37 patients,” Dr. Erdrich said.
The study analyzed pathological characteristics of the metastatic and nonmetastatic groups. Most characteristics were similar between the two groups, including location of the primary tumor in the trunk and extremities of 67% and 71%, respectively, and age of 60 years and older. The analysis noted two deviations: primary tumor size was thicker in the metastatic group (2.1 mm vs. 1.05 mm; P = .6), although Dr. Erdrich noted this was “not significantly different”; and a higher rate of ulceration in the metastatic group (50% vs. 13%; P = .05).
The genes CXCL1 and CXCL2 are both chemokines involved in growth and inflammation. “CXCL1 expression was 2.51 times greater in the metastatic group,” Dr. Erdrich said (P less than .001). Overexpression in the other three genes of interest was: CXCL2, 1.68 times greater (P less than .01); CD276, which is involved in T-cell immunity, 1.16 times greater (P = .04); and C-CBL, which is a photo-oncogene involved in the ubiquitin pathway, 1.15 times greater (P = .01). “The overexpression of all four of these was statistically significant,” she said.
Univariate analysis found ulceration of the primary along with overexpression of
the four genes to be significant predictors of metastasis. “However, in our multivariate model, three of the genes dropped out but CXCL1 remained robust,” she said.
Dr. Erdrich noted that CXCL1 is a cytokine located on chromosome 4, is secreted by macrophages, exerts its signal through CXCR2, and is one of five cytokines upregulated in lesions that respond to immunotherapy (Br J Dermatol. 2016;175:966-78).
CXCL1 compares favorably with S100, the existing blood-based biomarker for predicting recurrence in high-risk melanoma, as a predictor of metastases, Dr. Erdrich said, with an area under the curve of 0.80 versus 0.66; sensitivity of 67% versus 77%; specificity of 97% versus 61%; positive predictive value of 80% versus 40%; and negative predictive value of 94% versus 88% (Anticancer Res. 1999;19:2685-90; Cancer. 2003;97:1737-45).
The study also looked at overall survival in patients with low and high expression of CXCL1. “The patients with high expression had 5-year survival of only 50% compared to those of low expression, whose 5-year survival was 97%,” Dr. Erdrich said.
Dr. Erdrich and her coauthors reported having no financial relationships.
SOURCE: Erdrich J et al. SSO 2018, Abstract 82.
CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.
The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.
The rationale for analyzing the 79 genes implicated in cancer only rather than the entire array of 22,000 genes was to reduce the odds of a high false-discovery rate from 5% to 0.007%. “This is what strengthens our findings in a cohort of 37 patients,” Dr. Erdrich said.
The study analyzed pathological characteristics of the metastatic and nonmetastatic groups. Most characteristics were similar between the two groups, including location of the primary tumor in the trunk and extremities of 67% and 71%, respectively, and age of 60 years and older. The analysis noted two deviations: primary tumor size was thicker in the metastatic group (2.1 mm vs. 1.05 mm; P = .6), although Dr. Erdrich noted this was “not significantly different”; and a higher rate of ulceration in the metastatic group (50% vs. 13%; P = .05).
The genes CXCL1 and CXCL2 are both chemokines involved in growth and inflammation. “CXCL1 expression was 2.51 times greater in the metastatic group,” Dr. Erdrich said (P less than .001). Overexpression in the other three genes of interest was: CXCL2, 1.68 times greater (P less than .01); CD276, which is involved in T-cell immunity, 1.16 times greater (P = .04); and C-CBL, which is a photo-oncogene involved in the ubiquitin pathway, 1.15 times greater (P = .01). “The overexpression of all four of these was statistically significant,” she said.
Univariate analysis found ulceration of the primary along with overexpression of
the four genes to be significant predictors of metastasis. “However, in our multivariate model, three of the genes dropped out but CXCL1 remained robust,” she said.
Dr. Erdrich noted that CXCL1 is a cytokine located on chromosome 4, is secreted by macrophages, exerts its signal through CXCR2, and is one of five cytokines upregulated in lesions that respond to immunotherapy (Br J Dermatol. 2016;175:966-78).
CXCL1 compares favorably with S100, the existing blood-based biomarker for predicting recurrence in high-risk melanoma, as a predictor of metastases, Dr. Erdrich said, with an area under the curve of 0.80 versus 0.66; sensitivity of 67% versus 77%; specificity of 97% versus 61%; positive predictive value of 80% versus 40%; and negative predictive value of 94% versus 88% (Anticancer Res. 1999;19:2685-90; Cancer. 2003;97:1737-45).
The study also looked at overall survival in patients with low and high expression of CXCL1. “The patients with high expression had 5-year survival of only 50% compared to those of low expression, whose 5-year survival was 97%,” Dr. Erdrich said.
Dr. Erdrich and her coauthors reported having no financial relationships.
SOURCE: Erdrich J et al. SSO 2018, Abstract 82.
REPORTING FROM SSO 2018
Key clinical point: The CXCL1 gene may predict metastatic risk in primary melanoma.
Major findings: CXCL1 overexpression yielded 50% 5-year survival, almost half that of underexpression.
Study details: Gene analysis of samples from 37 patients with nonmetastatic primary melanoma who had surgical removal of primary lesion with median follow-up of 38 months.
Disclosures: Dr. Erdrich and her coauthors reported having no financial disclosures.
Source: Erdrich J et al. SSO 2018, Abstract 82.