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Concomitant drugs may explain PEG-ASP liver toxicities in ALL
STOCKHOLM – Liver toxicities in adults with acute lymphoblastic leukemia (ALL) treated with a pediatric-type regimen containing pegylated asparaginase (PEG-ASP) may be related to concomitant use of other hepatotoxic drugs, investigators cautioned.
A retrospective review of records on 26 adult ALL patients treated with PEG-ASP since 2013 showed that concomitant use of vincristine, idarubicin, and vancomycin was associated with an increased risk for grade 3 or 4 hepatotoxicity, reported Fabio Guolo, MD, from the University of Genoa (Italy) and his colleagues.
In contrast, patients who received other chemotherapy drugs or antimicrobial agents did not have significant liver toxicities, Dr. Guolo said in an interview at the annual congress of the European Hematology Association.
“Increased toxicity from therapy prevents delivery of the most active therapy, and asparaginase is one of the keys to the success of pediatric trials in ALL, so we have tried to push the dose of asparaginase as high as we could in adult patients,” he said.
“We asked why some patients will develop toxicity while receiving a relatively low dose of asparaginase, whereas other patients who received higher doses did not,” Dr. Guolo added.
In recent years, investigators have found that adults with ALL tend to have better outcomes when they were treated with standard pediatric ALL regimens, which includes high-dose PEG-ASP.
To identify factors related to potential PEG-ASP toxicity in adults with ALL, the investigators combed through records of 26 adults patients, 19 of whom had received PEG-ASP in the frontline setting, and 7 of whom received it during treatment of relapsed or refractory disease.
The investigators looked at each course of PEG-ASP as an independent event (51 total episodes), paying special attention to concomitant chemotherapy and the use of both antimycotic and antibiotic agents.
Five of the patients had grade 3 hepatotoxicity, and three had grade 4 hepatotoxicity. The patients with grade 4 events had unexplained severe weight gain and painful hepatomegaly. Ultrasonography in these patients revealed acute steatosis similar to that seen with sinusoidal occlusive disease. All three patients had received concomitant idarubicin, vincristine, and vancomycin.
In univariate analysis, neither being older than 45 years, administration of PEG-ASP during an active leukemia phase, nor having a body mass index greater than 25 kg/m2 were significantly associated with increased incidence of grade 3 or 4 hepatotoxicity.
When the investigators looked at concomitant chemotherapy drugs, however, they found that liver toxicity was significantly higher with idarubicin cumulative doses of 20 mg/m2 or greater (hazard ratio, 1.49; P = .047) and that vincristine doses of 2 mg/m2 or greater were associated with a borderline increase in risk (HR, 4.75; P = .055).
There was no increased risk for liver toxicities with either steroids, daunorubicin, cyclophosphamide, cytarabine, methotrexate, or 6-mercaptopurine.
Additionally, concomitant vancomycin was also linked to increased hepatotoxicity (HR, 1.86; P =.009). In contrast, neither carbapenem-class anti-infectives nor azole were significantly associated with liver toxicities.
“Notably, none of the patients undergoing full pediatric induction, which contains higher cumulative doses of PEG-ASP, experienced grade 4 hepatotoxicity regardless of age,” Dr. Guolo and his colleagues wrote in their poster presentation.
In multivariate analysis controlling for age, BMI, drug regimen, and concomitant therapies, idarubicin remained a significant risk factor for severe hepatotoxicity (P = .004), and vancomycin remained as a borderline risk (P = .054).
Dr. Guolo acknowledged that the investigators could not account for the potential contribution of over-the-counter medications with known risk for hepatotoxicity, such as acetaminophen.
He noted that in his group’s experience, the toxicity profile of PEG-ASP in adults, including high-dose regimens, was manageable without excess toxicities as long as clinicians paid close attention to the use of concomitant agents.
The study was internally funded. The authors reported having no relevant conflicts of interest.
SOURCE: Minetto P et al. EHA Congress, Abstract PS934.
STOCKHOLM – Liver toxicities in adults with acute lymphoblastic leukemia (ALL) treated with a pediatric-type regimen containing pegylated asparaginase (PEG-ASP) may be related to concomitant use of other hepatotoxic drugs, investigators cautioned.
A retrospective review of records on 26 adult ALL patients treated with PEG-ASP since 2013 showed that concomitant use of vincristine, idarubicin, and vancomycin was associated with an increased risk for grade 3 or 4 hepatotoxicity, reported Fabio Guolo, MD, from the University of Genoa (Italy) and his colleagues.
In contrast, patients who received other chemotherapy drugs or antimicrobial agents did not have significant liver toxicities, Dr. Guolo said in an interview at the annual congress of the European Hematology Association.
“Increased toxicity from therapy prevents delivery of the most active therapy, and asparaginase is one of the keys to the success of pediatric trials in ALL, so we have tried to push the dose of asparaginase as high as we could in adult patients,” he said.
“We asked why some patients will develop toxicity while receiving a relatively low dose of asparaginase, whereas other patients who received higher doses did not,” Dr. Guolo added.
In recent years, investigators have found that adults with ALL tend to have better outcomes when they were treated with standard pediatric ALL regimens, which includes high-dose PEG-ASP.
To identify factors related to potential PEG-ASP toxicity in adults with ALL, the investigators combed through records of 26 adults patients, 19 of whom had received PEG-ASP in the frontline setting, and 7 of whom received it during treatment of relapsed or refractory disease.
The investigators looked at each course of PEG-ASP as an independent event (51 total episodes), paying special attention to concomitant chemotherapy and the use of both antimycotic and antibiotic agents.
Five of the patients had grade 3 hepatotoxicity, and three had grade 4 hepatotoxicity. The patients with grade 4 events had unexplained severe weight gain and painful hepatomegaly. Ultrasonography in these patients revealed acute steatosis similar to that seen with sinusoidal occlusive disease. All three patients had received concomitant idarubicin, vincristine, and vancomycin.
In univariate analysis, neither being older than 45 years, administration of PEG-ASP during an active leukemia phase, nor having a body mass index greater than 25 kg/m2 were significantly associated with increased incidence of grade 3 or 4 hepatotoxicity.
When the investigators looked at concomitant chemotherapy drugs, however, they found that liver toxicity was significantly higher with idarubicin cumulative doses of 20 mg/m2 or greater (hazard ratio, 1.49; P = .047) and that vincristine doses of 2 mg/m2 or greater were associated with a borderline increase in risk (HR, 4.75; P = .055).
There was no increased risk for liver toxicities with either steroids, daunorubicin, cyclophosphamide, cytarabine, methotrexate, or 6-mercaptopurine.
Additionally, concomitant vancomycin was also linked to increased hepatotoxicity (HR, 1.86; P =.009). In contrast, neither carbapenem-class anti-infectives nor azole were significantly associated with liver toxicities.
“Notably, none of the patients undergoing full pediatric induction, which contains higher cumulative doses of PEG-ASP, experienced grade 4 hepatotoxicity regardless of age,” Dr. Guolo and his colleagues wrote in their poster presentation.
In multivariate analysis controlling for age, BMI, drug regimen, and concomitant therapies, idarubicin remained a significant risk factor for severe hepatotoxicity (P = .004), and vancomycin remained as a borderline risk (P = .054).
Dr. Guolo acknowledged that the investigators could not account for the potential contribution of over-the-counter medications with known risk for hepatotoxicity, such as acetaminophen.
He noted that in his group’s experience, the toxicity profile of PEG-ASP in adults, including high-dose regimens, was manageable without excess toxicities as long as clinicians paid close attention to the use of concomitant agents.
The study was internally funded. The authors reported having no relevant conflicts of interest.
SOURCE: Minetto P et al. EHA Congress, Abstract PS934.
STOCKHOLM – Liver toxicities in adults with acute lymphoblastic leukemia (ALL) treated with a pediatric-type regimen containing pegylated asparaginase (PEG-ASP) may be related to concomitant use of other hepatotoxic drugs, investigators cautioned.
A retrospective review of records on 26 adult ALL patients treated with PEG-ASP since 2013 showed that concomitant use of vincristine, idarubicin, and vancomycin was associated with an increased risk for grade 3 or 4 hepatotoxicity, reported Fabio Guolo, MD, from the University of Genoa (Italy) and his colleagues.
In contrast, patients who received other chemotherapy drugs or antimicrobial agents did not have significant liver toxicities, Dr. Guolo said in an interview at the annual congress of the European Hematology Association.
“Increased toxicity from therapy prevents delivery of the most active therapy, and asparaginase is one of the keys to the success of pediatric trials in ALL, so we have tried to push the dose of asparaginase as high as we could in adult patients,” he said.
“We asked why some patients will develop toxicity while receiving a relatively low dose of asparaginase, whereas other patients who received higher doses did not,” Dr. Guolo added.
In recent years, investigators have found that adults with ALL tend to have better outcomes when they were treated with standard pediatric ALL regimens, which includes high-dose PEG-ASP.
To identify factors related to potential PEG-ASP toxicity in adults with ALL, the investigators combed through records of 26 adults patients, 19 of whom had received PEG-ASP in the frontline setting, and 7 of whom received it during treatment of relapsed or refractory disease.
The investigators looked at each course of PEG-ASP as an independent event (51 total episodes), paying special attention to concomitant chemotherapy and the use of both antimycotic and antibiotic agents.
Five of the patients had grade 3 hepatotoxicity, and three had grade 4 hepatotoxicity. The patients with grade 4 events had unexplained severe weight gain and painful hepatomegaly. Ultrasonography in these patients revealed acute steatosis similar to that seen with sinusoidal occlusive disease. All three patients had received concomitant idarubicin, vincristine, and vancomycin.
In univariate analysis, neither being older than 45 years, administration of PEG-ASP during an active leukemia phase, nor having a body mass index greater than 25 kg/m2 were significantly associated with increased incidence of grade 3 or 4 hepatotoxicity.
When the investigators looked at concomitant chemotherapy drugs, however, they found that liver toxicity was significantly higher with idarubicin cumulative doses of 20 mg/m2 or greater (hazard ratio, 1.49; P = .047) and that vincristine doses of 2 mg/m2 or greater were associated with a borderline increase in risk (HR, 4.75; P = .055).
There was no increased risk for liver toxicities with either steroids, daunorubicin, cyclophosphamide, cytarabine, methotrexate, or 6-mercaptopurine.
Additionally, concomitant vancomycin was also linked to increased hepatotoxicity (HR, 1.86; P =.009). In contrast, neither carbapenem-class anti-infectives nor azole were significantly associated with liver toxicities.
“Notably, none of the patients undergoing full pediatric induction, which contains higher cumulative doses of PEG-ASP, experienced grade 4 hepatotoxicity regardless of age,” Dr. Guolo and his colleagues wrote in their poster presentation.
In multivariate analysis controlling for age, BMI, drug regimen, and concomitant therapies, idarubicin remained a significant risk factor for severe hepatotoxicity (P = .004), and vancomycin remained as a borderline risk (P = .054).
Dr. Guolo acknowledged that the investigators could not account for the potential contribution of over-the-counter medications with known risk for hepatotoxicity, such as acetaminophen.
He noted that in his group’s experience, the toxicity profile of PEG-ASP in adults, including high-dose regimens, was manageable without excess toxicities as long as clinicians paid close attention to the use of concomitant agents.
The study was internally funded. The authors reported having no relevant conflicts of interest.
SOURCE: Minetto P et al. EHA Congress, Abstract PS934.
REPORTING FROM EHA CONGRESS
Key clinical point:
Major finding: Idarubicin was associated with a higher risk of grade 3 or 4 hepatotoxicity, and vincristine was associated with a borderline risk.
Study details: Retrospective review of 51 PEG-ASP dosing events in 26 adult patients with ALL.
Disclosures: The study was internally funded. The authors reported having no relevant conflicts of interest.
Source: Minetto P et al. EHA Congress, Abstract PS934.
What Is the Prevalence of Sleep Disorders in Neurologic Populations?
A retrospective study finds that insomnia may be associated with worse neurologic status in patients with movement disorders and patients with epilepsy.
LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.
“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.
Analyzing STOP and Insomnia Severity Index Scores
OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.
In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.
The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.
The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.
Disease-Specific Outcomes
The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).
Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.
Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.
OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.
—Jake Remaly
A retrospective study finds that insomnia may be associated with worse neurologic status in patients with movement disorders and patients with epilepsy.
A retrospective study finds that insomnia may be associated with worse neurologic status in patients with movement disorders and patients with epilepsy.
LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.
“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.
Analyzing STOP and Insomnia Severity Index Scores
OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.
In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.
The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.
The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.
Disease-Specific Outcomes
The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).
Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.
Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.
OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.
—Jake Remaly
LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.
“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.
Analyzing STOP and Insomnia Severity Index Scores
OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.
In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.
The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.
The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.
Disease-Specific Outcomes
The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).
Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.
Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.
OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.
—Jake Remaly
Sleep Paralysis and Hallucinations Are Prevalent in Student Athletes
These symptoms may predict depression severity, independent of short sleep and insomnia.
BALTIMORE—Many student athletes have sleep paralysis and hypnagogic or hypnopompic hallucinations, according to research presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, these sleep symptoms are independently associated with symptoms of depression.
“These sleep symptoms are usually harmless on their own, but they can be a sign of more serious sleep problems,” said Serena Liu, a student research assistant in the Sleep and Health Research Program at the University of Arizona College of Medicine in Tucson. “The fact that they are so common among student athletes suggests that this is a group with some significant sleep problems that should be evaluated and dealt with.”
A Study of NCAA Athletes
Student athletes often have difficulty finding time to rest because of their busy schedules. Shorter sleep duration and poor sleep quality contribute to disordered sleep in many student athletes, and data indicate a high prevalence of common sleep symptoms in this group. Investigators have not studied the prevalence of less common symptoms (eg, sleep paralysis and hypnagogic and hypnopompic hallucinations, which are more prevalent in younger adults) in student athletes, however. Nor have they examined the potential role of these symptoms in mental health, independent of insufficient sleep duration or insomnia.
Ms. Liu and colleagues collected data from 189 student athletes in the National Collegiate Athletic Association’s Division I. The researchers asked the athletes how often they had sleep paralysis and hypnagogic or hypnopompic hallucinations. Responses were “never,” “rarely (once per month or less),” or “often (once or more per week).” Participants also gave information about sleep duration and underwent evaluation with the Insomnia Severity Index and the Centers for Epidemiological Studies Depression Scale. Ms. Liu and colleagues performed regression analyses to examine depression score as outcome and sleep symptoms as predictor in a model adjusted for age and sex and a model adjusted for age, sex, insomnia severity, and sleep duration.
Sleep Symptoms May Indicate Other Problems
About 18% of the sample reported having sleep paralysis rarely, and 7% reported having it often. In addition, 24% of the sample reported having hypnagogic or hypnopompic hallucinations rarely, and 11% reported having them often. In models adjusted for age and sex, reporting sleep paralysis rarely and often were associated with higher depression score, compared with reporting them never. Similarly, reporting hypnagogic and hypnopompic hallucinations rarely and often were associated with higher depression score. In models adjusted for insomnia and sleep duration, these relationships were attenuated, but remained significant.
These symptoms may predict depression severity, independent of short sleep and insomnia.
These symptoms may predict depression severity, independent of short sleep and insomnia.
BALTIMORE—Many student athletes have sleep paralysis and hypnagogic or hypnopompic hallucinations, according to research presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, these sleep symptoms are independently associated with symptoms of depression.
“These sleep symptoms are usually harmless on their own, but they can be a sign of more serious sleep problems,” said Serena Liu, a student research assistant in the Sleep and Health Research Program at the University of Arizona College of Medicine in Tucson. “The fact that they are so common among student athletes suggests that this is a group with some significant sleep problems that should be evaluated and dealt with.”
A Study of NCAA Athletes
Student athletes often have difficulty finding time to rest because of their busy schedules. Shorter sleep duration and poor sleep quality contribute to disordered sleep in many student athletes, and data indicate a high prevalence of common sleep symptoms in this group. Investigators have not studied the prevalence of less common symptoms (eg, sleep paralysis and hypnagogic and hypnopompic hallucinations, which are more prevalent in younger adults) in student athletes, however. Nor have they examined the potential role of these symptoms in mental health, independent of insufficient sleep duration or insomnia.
Ms. Liu and colleagues collected data from 189 student athletes in the National Collegiate Athletic Association’s Division I. The researchers asked the athletes how often they had sleep paralysis and hypnagogic or hypnopompic hallucinations. Responses were “never,” “rarely (once per month or less),” or “often (once or more per week).” Participants also gave information about sleep duration and underwent evaluation with the Insomnia Severity Index and the Centers for Epidemiological Studies Depression Scale. Ms. Liu and colleagues performed regression analyses to examine depression score as outcome and sleep symptoms as predictor in a model adjusted for age and sex and a model adjusted for age, sex, insomnia severity, and sleep duration.
Sleep Symptoms May Indicate Other Problems
About 18% of the sample reported having sleep paralysis rarely, and 7% reported having it often. In addition, 24% of the sample reported having hypnagogic or hypnopompic hallucinations rarely, and 11% reported having them often. In models adjusted for age and sex, reporting sleep paralysis rarely and often were associated with higher depression score, compared with reporting them never. Similarly, reporting hypnagogic and hypnopompic hallucinations rarely and often were associated with higher depression score. In models adjusted for insomnia and sleep duration, these relationships were attenuated, but remained significant.
BALTIMORE—Many student athletes have sleep paralysis and hypnagogic or hypnopompic hallucinations, according to research presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, these sleep symptoms are independently associated with symptoms of depression.
“These sleep symptoms are usually harmless on their own, but they can be a sign of more serious sleep problems,” said Serena Liu, a student research assistant in the Sleep and Health Research Program at the University of Arizona College of Medicine in Tucson. “The fact that they are so common among student athletes suggests that this is a group with some significant sleep problems that should be evaluated and dealt with.”
A Study of NCAA Athletes
Student athletes often have difficulty finding time to rest because of their busy schedules. Shorter sleep duration and poor sleep quality contribute to disordered sleep in many student athletes, and data indicate a high prevalence of common sleep symptoms in this group. Investigators have not studied the prevalence of less common symptoms (eg, sleep paralysis and hypnagogic and hypnopompic hallucinations, which are more prevalent in younger adults) in student athletes, however. Nor have they examined the potential role of these symptoms in mental health, independent of insufficient sleep duration or insomnia.
Ms. Liu and colleagues collected data from 189 student athletes in the National Collegiate Athletic Association’s Division I. The researchers asked the athletes how often they had sleep paralysis and hypnagogic or hypnopompic hallucinations. Responses were “never,” “rarely (once per month or less),” or “often (once or more per week).” Participants also gave information about sleep duration and underwent evaluation with the Insomnia Severity Index and the Centers for Epidemiological Studies Depression Scale. Ms. Liu and colleagues performed regression analyses to examine depression score as outcome and sleep symptoms as predictor in a model adjusted for age and sex and a model adjusted for age, sex, insomnia severity, and sleep duration.
Sleep Symptoms May Indicate Other Problems
About 18% of the sample reported having sleep paralysis rarely, and 7% reported having it often. In addition, 24% of the sample reported having hypnagogic or hypnopompic hallucinations rarely, and 11% reported having them often. In models adjusted for age and sex, reporting sleep paralysis rarely and often were associated with higher depression score, compared with reporting them never. Similarly, reporting hypnagogic and hypnopompic hallucinations rarely and often were associated with higher depression score. In models adjusted for insomnia and sleep duration, these relationships were attenuated, but remained significant.
High-Intensity Interval Exercise May Be Appropriate for Patients With MS
The activity is as enjoyable as continuous exercise for this population and could improve physiologic conditioning.
NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.
MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.
Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.
Dr. Hubbard and colleagues observed no significant condition-by-time interactions or main effects of condition on any POMS subscales. The data indicated large, statistically significant main effects of time on total mood disturbance, fatigue, and vigor. Specifically, mood worsened immediately after exercise, but rebounded after the 30-minute recovery period. The researchers saw no significant difference in scores for the PACES questionnaire between high-intensity interval exercise (mean, 95.5) and continuous exercise (mean, 97.7) conditions.
One weakness of the study was that the population was relatively active, although with a low level of fitness. In addition, the researchers did not control for age, sex, or disability status.
The high-intensity interval exercise and continuous exercise were feasible, safe, and enjoyable in people with MS who have mobility disability. “High-intensity interval exercise … might be particularly beneficial for improving fitness and functional capacity in persons with MS who have mobility disability and experience subsequent physiologic deconditioning,” said Dr. Hubbard.
The activity is as enjoyable as continuous exercise for this population and could improve physiologic conditioning.
The activity is as enjoyable as continuous exercise for this population and could improve physiologic conditioning.
NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.
MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.
Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.
Dr. Hubbard and colleagues observed no significant condition-by-time interactions or main effects of condition on any POMS subscales. The data indicated large, statistically significant main effects of time on total mood disturbance, fatigue, and vigor. Specifically, mood worsened immediately after exercise, but rebounded after the 30-minute recovery period. The researchers saw no significant difference in scores for the PACES questionnaire between high-intensity interval exercise (mean, 95.5) and continuous exercise (mean, 97.7) conditions.
One weakness of the study was that the population was relatively active, although with a low level of fitness. In addition, the researchers did not control for age, sex, or disability status.
The high-intensity interval exercise and continuous exercise were feasible, safe, and enjoyable in people with MS who have mobility disability. “High-intensity interval exercise … might be particularly beneficial for improving fitness and functional capacity in persons with MS who have mobility disability and experience subsequent physiologic deconditioning,” said Dr. Hubbard.
NASHVILLE—For patients with multiple sclerosis (MS) and walking impairments, high-intensity interval exercise is as enjoyable as traditional continuous exercise and does not induce sustained, harmful effects on mood, according to research presented at the 2018 CMSC Annual Meeting. This finding could influence evidence-based prescriptions for exercise that are appropriate for improving physiologic conditioning, according to the researchers.
MS often results in walking dysfunction and physiologic deconditioning. High-intensity interval exercise has induced significant improvements in physiologic conditioning in healthy and clinical populations, including patients with MS. Before integrating high-intensity interval exercise into an exercise prescription, and to increase the likelihood that participants will engage in and adhere to this exercise regimen, investigators thought it important to ascertain whether people with MS and mobility disability enjoy the high-intensity interval exercise and experience mood benefits.
Elizabeth Hubbard, PhD, Assistant Professor of Kinesiology at Berry College in Mount Berry, Georgia, conducted a study to examine the effects of single sessions of high-intensity interval exercise and continuous exercise on mood and enjoyment outcomes in persons with MS and mobility disability. In their study, 20 participants (median Expanded Disability Status Scale score, 5.8) underwent counterbalanced presentations of high-intensity interval exercise and continuous exercise bouts using a recumbent stepper. The high-intensity interval exercise bout was 20 minutes long and included 10 cycles of one-minute intervals at a wattage associated with 90% VO2 peak, followed by one-minute recovery intervals at 15 W. The continuous exercise bout lasted for 20 minutes at a wattage associated with 50% to 60% VO2 peak. The researchers administered the Profile of Mood States (POMS) survey before, immediately after, and 30 minutes after exercise. The Physical Activity Enjoyment Scale (PACES) questionnaire was administered immediately after exercise.
Dr. Hubbard and colleagues observed no significant condition-by-time interactions or main effects of condition on any POMS subscales. The data indicated large, statistically significant main effects of time on total mood disturbance, fatigue, and vigor. Specifically, mood worsened immediately after exercise, but rebounded after the 30-minute recovery period. The researchers saw no significant difference in scores for the PACES questionnaire between high-intensity interval exercise (mean, 95.5) and continuous exercise (mean, 97.7) conditions.
One weakness of the study was that the population was relatively active, although with a low level of fitness. In addition, the researchers did not control for age, sex, or disability status.
The high-intensity interval exercise and continuous exercise were feasible, safe, and enjoyable in people with MS who have mobility disability. “High-intensity interval exercise … might be particularly beneficial for improving fitness and functional capacity in persons with MS who have mobility disability and experience subsequent physiologic deconditioning,” said Dr. Hubbard.
Introducing the 2018 class of AGA Research Foundation awardees
The American Gastroenterological Association (AGA) and the AGA Research Foundation are pleased to award 41 investigators with more than $2 million in research funding in the 2018 award year.
“We were impressed by the quality of applications received in 2018,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “The AGA Research Foundation is excited to add 41 investigators into the AGA Research Foundation awards family and we look forward to seeing the results of their research. Based on the proposals, we are confident that the newest class of awardees will continue to push gastroenterology and hepatology research forward and contribute to the next big discoveries in our field.”
The AGA Research Foundation Awards Program recruits, retains, and supports the most promising investigators in gastroenterology and hepatology. With AGA Research Foundation funding, recipients have protected time to continue their fundamental research into causes and treatments for digestive disorders. AGA grants have launched the careers of investigators doing important work that translates to new patient care tools for clinicians and better outcomes for patients. To view the list of recipients go to https://www.gastro.org/press-release/introducing-the-2018-class-of-aga-research-foundation-awardees.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Learn more about the AGA Research Foundation at www.gastro.org/foundation.
The American Gastroenterological Association (AGA) and the AGA Research Foundation are pleased to award 41 investigators with more than $2 million in research funding in the 2018 award year.
“We were impressed by the quality of applications received in 2018,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “The AGA Research Foundation is excited to add 41 investigators into the AGA Research Foundation awards family and we look forward to seeing the results of their research. Based on the proposals, we are confident that the newest class of awardees will continue to push gastroenterology and hepatology research forward and contribute to the next big discoveries in our field.”
The AGA Research Foundation Awards Program recruits, retains, and supports the most promising investigators in gastroenterology and hepatology. With AGA Research Foundation funding, recipients have protected time to continue their fundamental research into causes and treatments for digestive disorders. AGA grants have launched the careers of investigators doing important work that translates to new patient care tools for clinicians and better outcomes for patients. To view the list of recipients go to https://www.gastro.org/press-release/introducing-the-2018-class-of-aga-research-foundation-awardees.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Learn more about the AGA Research Foundation at www.gastro.org/foundation.
The American Gastroenterological Association (AGA) and the AGA Research Foundation are pleased to award 41 investigators with more than $2 million in research funding in the 2018 award year.
“We were impressed by the quality of applications received in 2018,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “The AGA Research Foundation is excited to add 41 investigators into the AGA Research Foundation awards family and we look forward to seeing the results of their research. Based on the proposals, we are confident that the newest class of awardees will continue to push gastroenterology and hepatology research forward and contribute to the next big discoveries in our field.”
The AGA Research Foundation Awards Program recruits, retains, and supports the most promising investigators in gastroenterology and hepatology. With AGA Research Foundation funding, recipients have protected time to continue their fundamental research into causes and treatments for digestive disorders. AGA grants have launched the careers of investigators doing important work that translates to new patient care tools for clinicians and better outcomes for patients. To view the list of recipients go to https://www.gastro.org/press-release/introducing-the-2018-class-of-aga-research-foundation-awardees.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Learn more about the AGA Research Foundation at www.gastro.org/foundation.
AGA announces its newest class of Fellows
AGA Fellowship status is an honor awarded to members who demonstrate a personal commitment to the field of gastroenterology, as well as professional achievement in clinical private or academic practice and in basic or clinical research.
The most recent inductees into the AGA Fellows Program were recognized at Digestive Disease Week® (DDW) 2018 and received a digital ribbon in their AGA Community profile. The 2018 class of AGA Fellows includes 112 members, who added the designation “AGAF” in their professional activities.
Join the AGA Fellowship Recognition Panel in congratulating these distinguished members and view the 2018 class of AGA Fellows in the AGA Community forum, community.gastro.org
Learn more about joining this international community of excellence. Applications for the 2019 cohort are now being accepted. Those in clinical private or academic practice and in basic or clinical research who meet the AGAF criteria are invited to apply. Applications are due Aug. 27, 2018. Learn more at gastro.org/fellowship.
AGA Fellowship status is an honor awarded to members who demonstrate a personal commitment to the field of gastroenterology, as well as professional achievement in clinical private or academic practice and in basic or clinical research.
The most recent inductees into the AGA Fellows Program were recognized at Digestive Disease Week® (DDW) 2018 and received a digital ribbon in their AGA Community profile. The 2018 class of AGA Fellows includes 112 members, who added the designation “AGAF” in their professional activities.
Join the AGA Fellowship Recognition Panel in congratulating these distinguished members and view the 2018 class of AGA Fellows in the AGA Community forum, community.gastro.org
Learn more about joining this international community of excellence. Applications for the 2019 cohort are now being accepted. Those in clinical private or academic practice and in basic or clinical research who meet the AGAF criteria are invited to apply. Applications are due Aug. 27, 2018. Learn more at gastro.org/fellowship.
AGA Fellowship status is an honor awarded to members who demonstrate a personal commitment to the field of gastroenterology, as well as professional achievement in clinical private or academic practice and in basic or clinical research.
The most recent inductees into the AGA Fellows Program were recognized at Digestive Disease Week® (DDW) 2018 and received a digital ribbon in their AGA Community profile. The 2018 class of AGA Fellows includes 112 members, who added the designation “AGAF” in their professional activities.
Join the AGA Fellowship Recognition Panel in congratulating these distinguished members and view the 2018 class of AGA Fellows in the AGA Community forum, community.gastro.org
Learn more about joining this international community of excellence. Applications for the 2019 cohort are now being accepted. Those in clinical private or academic practice and in basic or clinical research who meet the AGAF criteria are invited to apply. Applications are due Aug. 27, 2018. Learn more at gastro.org/fellowship.
How does the Quality Payment Program affect you?
AGA asks Congress and CMS to continue to implement the Quality Payment Program (QPP) in a way that maximizes flexibility and success for you and your Medicare patients.
Most gastroenterologists participate in the Merit-Based Incentive Payment System (MIPS), which means how the QPP is implemented impacts the entire GI profession. The QPP replaced the sustainable growth rate (SGR) formula in 2015 when the Medicare Access and CHIP Reauthorization Act (MACRA) was signed into law. The QPP is comprised of two tracks: MIPS and Advanced Alternative Payment Models (Advanced APMs).
CMS has designated 2017 and 2018 as transition years to allow providers to learn about the QPP and to gradually increase their preparedness for MIPS.
Congress also recently acted to provide CMS additional flexibility with respect to QPP and MIPS implementation, including:
• Excluding Medicare Part B drug costs from MIPS payment adjustments.
• Eliminating improvement scoring for the cost performance category for the second through fifth years of MIPS.
• Allowing CMS to weight the cost performance category at less than 30 percent, but not less than 10 percent for the second through fifth years of MIPS.
• Allowing CMS flexibility in setting the performance threshold for MIPS in years two through five to ensure a gradual and incremental transition to the performance threshold set at the mean or median for the sixth year.
QPP implementation is a top priority for AGA to ensure that the value of specialty care is recognized. Learn more on our website www.gastro.org/QPP.
AGA asks Congress and CMS to continue to implement the Quality Payment Program (QPP) in a way that maximizes flexibility and success for you and your Medicare patients.
Most gastroenterologists participate in the Merit-Based Incentive Payment System (MIPS), which means how the QPP is implemented impacts the entire GI profession. The QPP replaced the sustainable growth rate (SGR) formula in 2015 when the Medicare Access and CHIP Reauthorization Act (MACRA) was signed into law. The QPP is comprised of two tracks: MIPS and Advanced Alternative Payment Models (Advanced APMs).
CMS has designated 2017 and 2018 as transition years to allow providers to learn about the QPP and to gradually increase their preparedness for MIPS.
Congress also recently acted to provide CMS additional flexibility with respect to QPP and MIPS implementation, including:
• Excluding Medicare Part B drug costs from MIPS payment adjustments.
• Eliminating improvement scoring for the cost performance category for the second through fifth years of MIPS.
• Allowing CMS to weight the cost performance category at less than 30 percent, but not less than 10 percent for the second through fifth years of MIPS.
• Allowing CMS flexibility in setting the performance threshold for MIPS in years two through five to ensure a gradual and incremental transition to the performance threshold set at the mean or median for the sixth year.
QPP implementation is a top priority for AGA to ensure that the value of specialty care is recognized. Learn more on our website www.gastro.org/QPP.
AGA asks Congress and CMS to continue to implement the Quality Payment Program (QPP) in a way that maximizes flexibility and success for you and your Medicare patients.
Most gastroenterologists participate in the Merit-Based Incentive Payment System (MIPS), which means how the QPP is implemented impacts the entire GI profession. The QPP replaced the sustainable growth rate (SGR) formula in 2015 when the Medicare Access and CHIP Reauthorization Act (MACRA) was signed into law. The QPP is comprised of two tracks: MIPS and Advanced Alternative Payment Models (Advanced APMs).
CMS has designated 2017 and 2018 as transition years to allow providers to learn about the QPP and to gradually increase their preparedness for MIPS.
Congress also recently acted to provide CMS additional flexibility with respect to QPP and MIPS implementation, including:
• Excluding Medicare Part B drug costs from MIPS payment adjustments.
• Eliminating improvement scoring for the cost performance category for the second through fifth years of MIPS.
• Allowing CMS to weight the cost performance category at less than 30 percent, but not less than 10 percent for the second through fifth years of MIPS.
• Allowing CMS flexibility in setting the performance threshold for MIPS in years two through five to ensure a gradual and incremental transition to the performance threshold set at the mean or median for the sixth year.
QPP implementation is a top priority for AGA to ensure that the value of specialty care is recognized. Learn more on our website www.gastro.org/QPP.
AGA opens GI Patient Center to the public
We’re proud to announce the public launch of the AGA GI Patient Center, an online hub for digestive health information developed by specialists, for patients. The GI Patient Center – previously only accessible by AGA member physicians – now directly provides patients with trusted information on a variety of GI conditions and procedures.
Browse the GI Patient Center, which includes information on more than 30 topics, available in both English and Spanish. All AGA patient education was written and reviewed by leading gastroenterologists, and developed with health literacy in mind.
You can print this information for your practice, email patients a link, include a link on your website – whatever is needed to ensure your patients are getting trusted health information about their condition, treatment, or procedure.
To get started, visit patient.gastro.org.
We’re proud to announce the public launch of the AGA GI Patient Center, an online hub for digestive health information developed by specialists, for patients. The GI Patient Center – previously only accessible by AGA member physicians – now directly provides patients with trusted information on a variety of GI conditions and procedures.
Browse the GI Patient Center, which includes information on more than 30 topics, available in both English and Spanish. All AGA patient education was written and reviewed by leading gastroenterologists, and developed with health literacy in mind.
You can print this information for your practice, email patients a link, include a link on your website – whatever is needed to ensure your patients are getting trusted health information about their condition, treatment, or procedure.
To get started, visit patient.gastro.org.
We’re proud to announce the public launch of the AGA GI Patient Center, an online hub for digestive health information developed by specialists, for patients. The GI Patient Center – previously only accessible by AGA member physicians – now directly provides patients with trusted information on a variety of GI conditions and procedures.
Browse the GI Patient Center, which includes information on more than 30 topics, available in both English and Spanish. All AGA patient education was written and reviewed by leading gastroenterologists, and developed with health literacy in mind.
You can print this information for your practice, email patients a link, include a link on your website – whatever is needed to ensure your patients are getting trusted health information about their condition, treatment, or procedure.
To get started, visit patient.gastro.org.
Phase 3 trial: Tasimelteon effective for jet lag disorder
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
BALTIMORE – Tasimelteon, a drug approved for non–24-hour sleep-wake disorder, has been shown to increase sleep times in travelers with jet lag, according to results from a phase 3 trial.
“Tasimelteon demonstrated an increase in total sleep time of 85 minutes versus placebo and also demonstrated improvement in next-day alertness versus placebo,” Christos Polymeropoulos, MD, medical director of Vanda Pharmaceuticals, said in presenting results of the JET8 trial during the late-breaking abstracts session at the annual meeting of the Associated Professional Sleep Societies.
Tasimelteon, sold under the trade name Hetlioz, is a melatonin receptor agonist that is Food and Drug Administration–approved for non-24-hour sleep-wake disorder – but not for treatment of jet lag disorder (JLD). Dr. Polymeropoulos noted there is no FDA-approved treatment for JLD.
“Jet lag disorder is a circadian disorder frequently observed in millions of travelers who cross multiple time zones,” Dr. Polymeropoulos said. “JLD is characterized by nighttime sleep disruption, decrease in daytime alertness, and impairment in social and occupational function.”
JET8 induced the circadian challenge equivalent to crossing eight time zones. The study involved 318 individuals randomized evenly to 20 mg tasimelteon or placebo 30 minutes before bedtime. The primary endpoint of the study was total sleep time in the first two-thirds of night measured by polysomnography.
Those on tasimelteon averaged 216.4 minutes of total sleep time in the first two-thirds of night versus 156.1 for those on placebo (P less than .0001), Dr. Polymeropoulos said. Full total sleep times were 315.8 minutes versus 230.3 minutes (P less than .0001), respectively.
“For total sleep time, the tasimelteon subjects gained about an hour and a half, as measured by PSG [polysomnography],” Dr. Polymeropoulos said.
Other key markers the trial measured were latency to persistent sleep and wakefulness after sleep onset. They measured 15 minutes less and 74.6 minutes less, respectively, in the tasimelteon arm.
Dr. Polymeropoulos also disclosed early results of a second trial of tasimelteon in JLD: the JET Study, a two-phase transatlantic travel study of 25 patients. The subjects flew from four U.S. cities to London for 3 nights, receiving tasimelteon or placebo each night in London. The study was terminated before reaching its enrollment goal of 90 patients because of its complexity, Vanda said in a separate press release. Over 3 nights of study, the tasimelteon arm gained a total of about 130 minutes of sleep versus 40 minutes for the placebo arm, Dr. Polymeropoulos said.
Vanda has said it plans to file a supplemental new drug application for tasimelteon for treatment of JLD in the second half of this year.
Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
REPORTING FROM SLEEP 2018
Key clinical point: The melatonin receptor agonist tasimelteon may improve sleep in jet lag.
Major finding: Total sleep times were 315.8 minutes for tasimelteon versus 230.3 for placebo.
Study details: JET8 randomized, double-blind, placebo-controlled, multicenter trial of 318 healthy subjects with induced jet lag disorder.
Disclosures: Dr. Polymeropoulos is an employee of Vanda Pharmaceuticals.
Study questions canagliflozin amputation risk, but concerns remain
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
REPORTING FROM ADA 2018
Key clinical point: A large, observational study found no increased risk of below-the-knee amputations with canagliflozin for type 2 diabetes, but clinicians should still favor other options in patients at risk for amputations.
Major finding: The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30).
Study details: An observational study of over 700,000 patients with type 2 diabetes.
Disclosures: The work was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of the presenter, conducted by its employees.