Sleep Medicine

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

[email protected]

SOURCE: Chung D et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

[email protected]

SOURCE: Chung D et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

[email protected]

SOURCE: Chung D et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Among patients who present with rhinologic symptoms, the 22-item Sinonasal Outcomes Test (SNOT-22) can help identify those with undiagnosed obstructive sleep apnea (OSA), results from a retrospective analysis demonstrated.

“We know based on experience and prior studies that there is significant overlap in symptoms for obstructive sleep apnea and chronic rhinosinusitis [CRS], which are two common conditions in the general population,” one of the study authors, David W. Jang, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Therefore, it is important to identify patients with undiagnosed OSA who may present to the physician with nose- and sinus-related symptoms.”

Dr. Jang, assistant professor of rhinology and endoscopic skull surgery in the department of surgery at Duke University, Durham, N.C., and his colleagues conducted a 3-year retrospective analysis of 165 adults who presented with a rhinologic chief complaint and completed the SNOT-22 survey. The researchers compared SNOT-22 survey results between patients with untreated OSA confirmed on polysomnography without chronic rhinosinusitis and a control group of CRS patients. A chi-square test with Bonferroni correction was used for analysis.

Of the 165 patients, 41 met criteria for untreated OSA, based on a mean apnea-hypopnea index of 29.3, while 124 were included in the CRS control group. Sleep and psychological domain scores were not significantly different between the two groups, although patients in the OSA group were more likely to choose a sleep-related symptom as their most important complaint (MIC) (P less than .001). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (P less than .001), while facial pain and nasal obstruction were not significantly different (P = .117 and P = .198, respectively). Facial pain and nasal obstruction were the most common MICs in the rhinologic domain for OSA patients; thick nasal discharge and postnasal discharge were the most common MICs reported by patients in the CRS group.

[email protected]

CORONADO, CALIF. – Among patients who present with rhinologic symptoms, the 22-item Sinonasal Outcomes Test (SNOT-22) can help identify those with undiagnosed obstructive sleep apnea (OSA), results from a retrospective analysis demonstrated.

“We know based on experience and prior studies that there is significant overlap in symptoms for obstructive sleep apnea and chronic rhinosinusitis [CRS], which are two common conditions in the general population,” one of the study authors, David W. Jang, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Therefore, it is important to identify patients with undiagnosed OSA who may present to the physician with nose- and sinus-related symptoms.”

Dr. Jang, assistant professor of rhinology and endoscopic skull surgery in the department of surgery at Duke University, Durham, N.C., and his colleagues conducted a 3-year retrospective analysis of 165 adults who presented with a rhinologic chief complaint and completed the SNOT-22 survey. The researchers compared SNOT-22 survey results between patients with untreated OSA confirmed on polysomnography without chronic rhinosinusitis and a control group of CRS patients. A chi-square test with Bonferroni correction was used for analysis.

Of the 165 patients, 41 met criteria for untreated OSA, based on a mean apnea-hypopnea index of 29.3, while 124 were included in the CRS control group. Sleep and psychological domain scores were not significantly different between the two groups, although patients in the OSA group were more likely to choose a sleep-related symptom as their most important complaint (MIC) (P less than .001). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (P less than .001), while facial pain and nasal obstruction were not significantly different (P = .117 and P = .198, respectively). Facial pain and nasal obstruction were the most common MICs in the rhinologic domain for OSA patients; thick nasal discharge and postnasal discharge were the most common MICs reported by patients in the CRS group.

[email protected]

CORONADO, CALIF. – Among patients who present with rhinologic symptoms, the 22-item Sinonasal Outcomes Test (SNOT-22) can help identify those with undiagnosed obstructive sleep apnea (OSA), results from a retrospective analysis demonstrated.

“We know based on experience and prior studies that there is significant overlap in symptoms for obstructive sleep apnea and chronic rhinosinusitis [CRS], which are two common conditions in the general population,” one of the study authors, David W. Jang, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Therefore, it is important to identify patients with undiagnosed OSA who may present to the physician with nose- and sinus-related symptoms.”

Dr. Jang, assistant professor of rhinology and endoscopic skull surgery in the department of surgery at Duke University, Durham, N.C., and his colleagues conducted a 3-year retrospective analysis of 165 adults who presented with a rhinologic chief complaint and completed the SNOT-22 survey. The researchers compared SNOT-22 survey results between patients with untreated OSA confirmed on polysomnography without chronic rhinosinusitis and a control group of CRS patients. A chi-square test with Bonferroni correction was used for analysis.

Of the 165 patients, 41 met criteria for untreated OSA, based on a mean apnea-hypopnea index of 29.3, while 124 were included in the CRS control group. Sleep and psychological domain scores were not significantly different between the two groups, although patients in the OSA group were more likely to choose a sleep-related symptom as their most important complaint (MIC) (P less than .001). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (P less than .001), while facial pain and nasal obstruction were not significantly different (P = .117 and P = .198, respectively). Facial pain and nasal obstruction were the most common MICs in the rhinologic domain for OSA patients; thick nasal discharge and postnasal discharge were the most common MICs reported by patients in the CRS group.

[email protected]

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

Numerous independent factors – including a history of obstructive/central sleep apnea syndrome (OSAS/CSAS) or myocardial infarction, along with a body mass index greater than 30 g/m² – could be related to ICU admission and subsequent high mortality rates in influenza patients, according to an analysis of patients in the Netherlands who were treated during the influenza epidemic of 2015-2016.

copyright Andrei Malov/Thinkstock

Along with determining these factors, lead author M.C. Beumer, of Radboud University Medical Center, the Netherlands, and his coauthors found that “coinfections with bacterial, fungal, and viral pathogens developed more often in patients who were admitted to the ICU.” The study was published in the Journal of Critical Care.

The coauthors reviewed 199 influenza patients who were admitted to two medical centers in the Netherlands during October 2015–April 2016. Of those patients, 45 (23%) were admitted to the ICU, primarily because of respiratory failure, and their mortality rate was 17/45 (38%) versus an overall mortality rate of 18/199 (9%).

Compared with patients in the normal ward, patients admitted to the ICU more frequently had a history of OSAS/CSAS (11% vs. 3%; P = .03) and MI (20% vs. 6%; P = .007), along with a BMI higher than 30 g/m² (30% vs. 15%; P = .04) and dyspnea as a symptom (77% vs. 48%,; P = .001). In addition, more ICU-admitted patients had influenza A rather than influenza B, compared with those not admitted (87% vs. 66%; P = .009).

Pulmonary coinfections – including bacterial, fungal, and viral pathogens – were also proportionally higher among the 45 ICU patients (56% vs. 20%; P less than .0001). The most common bacterial pathogens were Staphylococcus aureus (11%) and Streptococcus pneumoniae (7%) while Aspergillus fumigatus (18%) and Pneumocystis jirovecii (7%) topped the fungal pathogens.

Mr. Beumer and his colleagues noted potential limitations of their work, including the selection of patients from among the “most severely ill” contributing to an ICU admission rate that surpassed the 5%-10% described elsewhere. They also admitted that their study relied on a “relatively small sample size,” focusing on one seasonal influenza outbreak. However, “despite the limited validity,” they reiterated that “the identified factors may contribute to a complicated disease course and could represent a tool for early recognition of the influenza patients at risk for a complicated disease course.”

The authors reported no conflicts of interest.

SOURCE: Beumer MC et al. J Crit Care. 2019;50:59-65.



.

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

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Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Too little and too much sleep, along with fragmented sleep, were independently linked with increased subclinical, noncardiac atherosclerotic plaque in healthy middle-aged men and women in a Spanish investigation of bank employees.

Wavebreak Media/Thinkstockphotos

“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.

Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.

The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.

The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.

After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.

LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.

Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.

Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.

The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.

[email protected]

SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.

Too little and too much sleep, along with fragmented sleep, were independently linked with increased subclinical, noncardiac atherosclerotic plaque in healthy middle-aged men and women in a Spanish investigation of bank employees.

Wavebreak Media/Thinkstockphotos

“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.

Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.

The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.

The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.

After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.

LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.

Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.

Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.

The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.

[email protected]

SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.

Too little and too much sleep, along with fragmented sleep, were independently linked with increased subclinical, noncardiac atherosclerotic plaque in healthy middle-aged men and women in a Spanish investigation of bank employees.

Wavebreak Media/Thinkstockphotos

“Overall, our findings support the potential role of healthy sleeping in protecting against atherosclerosis. Thus, recommending a good sleep hygiene” – 7-8 hours a night – “should be part of the lifestyle modifications provided in our daily clinical practice,” said investigators led by Fernando Domínguez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid. The report is in the Journal of the American College of Cardiology.

Studies have linked sleep problems to increased cardiovascular risk before, but the investigations tended to focus on patients with obstructive sleep apnea (OSA) and other problems, and often relied on patient self-report. The investors wanted to see if the relationship held in healthy adults, using an objective measure.

The participants – all with no known cardiovascular disease – wore Acti Trainers accelerometers (Actigraph, Pensacola, Fla.) around their waists for 7 days to record sleep duration and quality. Subjects also had their plaque burdens assessed by 3-dimensional vascular ultrasound (VUS) at their carotid and femoral arteries bilaterally. Cardiac CT was used to assess coronary artery calcification as a surrogate for coronary artery atherosclerosis.

The 3,974 participants had a mean age of 46 years, and a third were women; they had a low prevalence of both hypertension and diabetes. OSA patients were excluded from the study. Overall, 27% had very short sleep duration (VSSD), less than 6 hours a night; 38% had short sleep duration (SSD), 31% slept from 7 to 8 hours per night, and served as the reference group for healthy sleep habits; and 4% had long sleep duration (LSD), greater than 8 hours.

After adjustment for a wide range of cardiovascular risk factors, including body mass index, hypertension, and smoking, VSSD was independently associated with a higher atherosclerotic burden, compared to the reference group (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). Participants in the highest quintile of sleep fragmentation were more likely to have plaques at multiple sites (OR, 1.34; 95% CI, 1.09-1.64; P = 0.006). The Framingham risk score at both 10 and 30 years was significantly higher in participants with VSSD or SSD, and in the highest quintiles of sleep fragmentation.

LSD was also associated with a higher plaque burden, which reached statistical significance in women. “Too-long sleep duration may not be healthy either ... Recommendations should be restricted to 7 to 8 hours,” the investigators said.

Sleep duration and quality were not associated with inflammation markers or coronary artery calcification. The investigators noted that CT for coronary artery calcification might not be as sensitive as VUS for picking up subclinical atherosclerosis.

Short sleepers tended to have higher intakes of alcohol and caffeine than did those in the 7- to 8-hour group.

The work was funded by CNIC and Banco Santander, among others. Dr. Domínguez had no disclosures. Investigator Hector Bueno, MD, PhD, reported research funding and fees from a number of companies, including AstraZeneca and Novartis. The second author, Valentín Fuster, MD, PhD, is the editor of the Journal of the American College of Cardiology, which published the report.

[email protected]

SOURCE: Domínguez F et al. J Am Coll Cardiol 2019;73:134-44.

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

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Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.