Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.

Comparing Lemborexant With Zolpidem

In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.

At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.

Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.

The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.

The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.

Comparing Lemborexant With Zopiclone

In a separate study, Annemiek Vermeeren, PhD, Assistant Pro­fessor of Neuropsychology and Psycho­pharmacology at Maastricht Uni­versity in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.

Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).

The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.

The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.

The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.

The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.

Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.

—Erik Greb

Suggested Reading

Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.

BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.

Comparing Lemborexant With Zolpidem

In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.

At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.

Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.

The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.

The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.

Comparing Lemborexant With Zopiclone

In a separate study, Annemiek Vermeeren, PhD, Assistant Pro­fessor of Neuropsychology and Psycho­pharmacology at Maastricht Uni­versity in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.

Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).

The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.

The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.

The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.

The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.

Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.

—Erik Greb

Suggested Reading

Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.

BALTIMORE—Lemborexant, an investigational treatment for insomnia, does not impair postural stability or driving ability on the morning after dosing, according to the results of phase I studies presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies. In addition, lemborexant does not impair the ability to be awakened at night and helps patients return to sleep faster than placebo. Lemborexant is a dual orexin receptor antagonist in development for the treatment of insomnia and irregular sleep–wake rhythm disorder.

Comparing Lemborexant With Zolpidem

In one double-blind study, Patricia Murphy, PhD, Director of Clinical Research at Eisai, and colleagues randomized 63 healthy volunteers to one of four treatment sequences. The treatments were 5 mg of lemborexant, 10 mg of lemborexant, 6.25 mg of zolpidem, and placebo. Treatments were administered five minutes before bedtime.

At about four hours after bedtime, participants were exposed through earbuds to a 15-dB tone that became 5 dB louder every 15 seconds. Investigators recorded the volume required to awaken the participants. Within five minutes of awakening, participants had their postural stability measured by ataxiameter. After this assessment, the investigators used polysomnography to measure the time it took for participants to fall asleep again. Finally, participants underwent a second postural stability measurement after awakening in the morning. Participants entered a washout period of at least 14 days after each treatment and repeated the same tests for each treatment.

Approximately 78% of the population was female, and the average age was 63.6. Neither lemborexant nor zolpidem significantly increased participants’ auditory awakening threshold (AAT), compared with placebo. The mean AAT was 50 dB for placebo, 51.8 dB for 5 mg of lemborexant, 51.7 dB for 10 mg of lemborexant, and 58.4 dB for zolpidem.

The 5-mg dose of lemborexant did not significantly decrease postural stability, compared with placebo, when participants were awakened at night. The 10-mg dose of lemborexant caused a clinically meaningful decrease in postural stability, and zolpidem was associated with a decrease in stability that was twice that seen with 10 mg of lemborexant.

The mean latency to return to sleep was 40.9 minutes for placebo, 18.1 minutes for 5 mg of lemborexant, 12.1 minutes for 10 mg of lemborexant, and 19.6 minutes for zolpidem. Neither dose of lemborexant significantly affected postural stability after eight hours of sleep. Zolpidem was associated with a significant decrease in postural stability, compared with placebo, but the increase was not clinically meaningful.

Comparing Lemborexant With Zopiclone

In a separate study, Annemiek Vermeeren, PhD, Assistant Pro­fessor of Neuropsychology and Psycho­pharmacology at Maastricht Uni­versity in the Netherlands, and colleagues evaluated whether lemborexant affected driving performance on the morning after dosing. They enrolled 48 healthy adults into the double-blind, incomplete crossover trial. Participants were randomized to one of 12 treatment sequences, and treatments included lemborexant (2.5 mg, 5 mg, or 10 mg) for eight consecutive days, zopiclone (7.5 mg) on Days 1 and 8 (with placebo on intervening days), and placebo for eight consecutive days. A washout period of at least 14 days followed each eight-day treatment period. Each participant received two of the three lemborexant doses.

Participants completed a practice driving test during screening, and driving performance was assessed at approximately nine hours after dosing on Days 2 and 9. Subjects were instructed to drive at 95 km/h within one lane for approximately one hour, while instruments on the vehicle measured their standard deviation of lateral position (SDLP).

The population’s mean age was 58.5, and 54.2% of participants were male. The mean increases from placebo in SDLP were less than 0.75 cm on both test days after all doses of lemborexant. These changes were neither statistically significant nor clinically meaningful. Zopiclone was associated with increases in SDLP of 2.04 cm on Day 2 and 1.88 cm on Day 9. These changes were statistically significant and clinically meaningful on both days.

The investigators categorized patients as between ages 21 and 65 or age 65 or older. The effects of lemborexant did not differ between adults older and younger than 65 or between males and females.

The driving instructor terminated three of 384 driving tests early. All participants whose tests were terminated had taken zopiclone.

The investigators did not observe any serious adverse events, severe treatment-emergent adverse events, or treatment-emergent adverse events leading to study discontinuation. The most common treatment-emergent adverse events reported after treatment with lemborexant were somnolence, headache, and dry mouth. The most common treatment-emergent adverse events reported after treatment with zopiclone were somnolence, dysgeusia, and dizziness.

Eisai and Purdue Pharma, the developers of lemborexant, funded the studies.

—Erik Greb

Suggested Reading

Murphy P, Moline M, Mayleben D, et al. Lemborexant, A dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289-1299.

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.

FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.

In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.

In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.

The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.

Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.

The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.

[email protected]

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.

FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.

In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.

In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.

The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.

Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.

The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.

[email protected]

The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.

FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.

In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.

In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.

The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.

Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.

The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.

[email protected]

BALTIMORE—Objective and subjective sleep measures are associated with fatigue in people with multiple sclerosis (MS), according to a meta-analysis presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies.

Evidence suggests that individuals with MS have disruptions in sleep that are associated with and may contribute to fatigue, said Jagriti “Jackie” Bhattarai, PhD, a postdoctoral fellow in the MS Rehabilitation Research Laboratory at the Johns Hopkins School of Medicine’s Department of Physical Medicine and Rehabilitation in Baltimore. Among the sleep parameters investigated, sleep staging, sleep-related movement, and subjective insomnia had moderate associations with fatigue. Other sleep parameters examined in the study were not statistically significantly associated with fatigue, she said.

A Major Factor in Disability

Fatigue is a leading contributor to disability in patients with MS. Although fatigue is a complex symptom with multiple neurologic and behavioral causes, emerging evidence suggests that “sleep disturbance may have a significant role in the development or maintenance of fatigue in MS,” Dr. Bhattarai said. The relationship between sleep parameters and fatigue in people with MS is not well understood, however, she said.

To examine the relationship between commonly used sleep parameters and fatigue in MS, Dr. Bhattarai and colleagues identified studies that included at least one validated measure of fatigue and one validated measure of sleep disturbance. They included studies that reported the effect sizes of the associations between sleep and fatigue or provided enough data for the investigators to compute the effect sizes.

Their meta-analysis included 37 studies with 6,129 participants. Participants had an average age of 42 and MS duration of 9.5 years. About 80% of the sample had relapsing-remitting MS.

Sleep measures included polysomnography, actigraphy, and the multiple sleep latency test, as well as subjective measures such as the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, and the Medical Outcomes Study Sleep Scale.

Fatigue was measured using the Fatigue Severity Scale, the modified Fatigue Impact Scale, or the Neurological Fatigue Index for MS.

Effect sizes varied across studies, as did the parameters examined within each study. The mean effect size was the largest for the association between REM sleep onset latency (ie, the time between sleep onset and initiation of REM sleep) and fatigue (r = 0.42), though this effect size was based on only two studies, and the association requires further investigation. “Shorter REM sleep onset latency has been associated with depression and narcolepsy,” both of which are more common in people with MS than in the general population, Dr. Bhattarai said. Subjective insomnia (r = 0.36) and objective sleep-related movement (r = 0.34) also yielded moderate effect sizes. “The shorter the REM sleep onset latency and the more subjective complaints that individuals have about their sleep, the greater the level of fatigue people with MS reported,” she said. “The more sleep-related movement that people have, the greater their level of MS-related fatigue.”

Potential to Inform Treatment Approach

The association between fatigue and objective sleep-disordered breathing was not statistically significant. Subjective sleep-disordered breathing, objective nocturnal arousals, sleep efficiency, sleep onset latency, and sleep duration had weak effect sizes. These problems are common and require treatment, however, Dr. Bhattarai said.

“When treating patients with MS who are experiencing MS-related fatigue, interventions geared toward improving patients’ perceived sleep quality and addressing MS symptoms that might disrupt sleep (eg, nocturia and periodic leg movements) may offer an avenue for improving fatigue,” said Dr. Bhattarai. “However, these effects remain to be shown in a randomized controlled trial.”

—Jake Remaly

BALTIMORE—Objective and subjective sleep measures are associated with fatigue in people with multiple sclerosis (MS), according to a meta-analysis presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies.

Evidence suggests that individuals with MS have disruptions in sleep that are associated with and may contribute to fatigue, said Jagriti “Jackie” Bhattarai, PhD, a postdoctoral fellow in the MS Rehabilitation Research Laboratory at the Johns Hopkins School of Medicine’s Department of Physical Medicine and Rehabilitation in Baltimore. Among the sleep parameters investigated, sleep staging, sleep-related movement, and subjective insomnia had moderate associations with fatigue. Other sleep parameters examined in the study were not statistically significantly associated with fatigue, she said.

A Major Factor in Disability

Fatigue is a leading contributor to disability in patients with MS. Although fatigue is a complex symptom with multiple neurologic and behavioral causes, emerging evidence suggests that “sleep disturbance may have a significant role in the development or maintenance of fatigue in MS,” Dr. Bhattarai said. The relationship between sleep parameters and fatigue in people with MS is not well understood, however, she said.

To examine the relationship between commonly used sleep parameters and fatigue in MS, Dr. Bhattarai and colleagues identified studies that included at least one validated measure of fatigue and one validated measure of sleep disturbance. They included studies that reported the effect sizes of the associations between sleep and fatigue or provided enough data for the investigators to compute the effect sizes.

Their meta-analysis included 37 studies with 6,129 participants. Participants had an average age of 42 and MS duration of 9.5 years. About 80% of the sample had relapsing-remitting MS.

Sleep measures included polysomnography, actigraphy, and the multiple sleep latency test, as well as subjective measures such as the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, and the Medical Outcomes Study Sleep Scale.

Fatigue was measured using the Fatigue Severity Scale, the modified Fatigue Impact Scale, or the Neurological Fatigue Index for MS.

Effect sizes varied across studies, as did the parameters examined within each study. The mean effect size was the largest for the association between REM sleep onset latency (ie, the time between sleep onset and initiation of REM sleep) and fatigue (r = 0.42), though this effect size was based on only two studies, and the association requires further investigation. “Shorter REM sleep onset latency has been associated with depression and narcolepsy,” both of which are more common in people with MS than in the general population, Dr. Bhattarai said. Subjective insomnia (r = 0.36) and objective sleep-related movement (r = 0.34) also yielded moderate effect sizes. “The shorter the REM sleep onset latency and the more subjective complaints that individuals have about their sleep, the greater the level of fatigue people with MS reported,” she said. “The more sleep-related movement that people have, the greater their level of MS-related fatigue.”

Potential to Inform Treatment Approach

The association between fatigue and objective sleep-disordered breathing was not statistically significant. Subjective sleep-disordered breathing, objective nocturnal arousals, sleep efficiency, sleep onset latency, and sleep duration had weak effect sizes. These problems are common and require treatment, however, Dr. Bhattarai said.

“When treating patients with MS who are experiencing MS-related fatigue, interventions geared toward improving patients’ perceived sleep quality and addressing MS symptoms that might disrupt sleep (eg, nocturia and periodic leg movements) may offer an avenue for improving fatigue,” said Dr. Bhattarai. “However, these effects remain to be shown in a randomized controlled trial.”

—Jake Remaly

BALTIMORE—Objective and subjective sleep measures are associated with fatigue in people with multiple sclerosis (MS), according to a meta-analysis presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies.

Evidence suggests that individuals with MS have disruptions in sleep that are associated with and may contribute to fatigue, said Jagriti “Jackie” Bhattarai, PhD, a postdoctoral fellow in the MS Rehabilitation Research Laboratory at the Johns Hopkins School of Medicine’s Department of Physical Medicine and Rehabilitation in Baltimore. Among the sleep parameters investigated, sleep staging, sleep-related movement, and subjective insomnia had moderate associations with fatigue. Other sleep parameters examined in the study were not statistically significantly associated with fatigue, she said.

A Major Factor in Disability

Fatigue is a leading contributor to disability in patients with MS. Although fatigue is a complex symptom with multiple neurologic and behavioral causes, emerging evidence suggests that “sleep disturbance may have a significant role in the development or maintenance of fatigue in MS,” Dr. Bhattarai said. The relationship between sleep parameters and fatigue in people with MS is not well understood, however, she said.

To examine the relationship between commonly used sleep parameters and fatigue in MS, Dr. Bhattarai and colleagues identified studies that included at least one validated measure of fatigue and one validated measure of sleep disturbance. They included studies that reported the effect sizes of the associations between sleep and fatigue or provided enough data for the investigators to compute the effect sizes.

Their meta-analysis included 37 studies with 6,129 participants. Participants had an average age of 42 and MS duration of 9.5 years. About 80% of the sample had relapsing-remitting MS.

Sleep measures included polysomnography, actigraphy, and the multiple sleep latency test, as well as subjective measures such as the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, and the Medical Outcomes Study Sleep Scale.

Fatigue was measured using the Fatigue Severity Scale, the modified Fatigue Impact Scale, or the Neurological Fatigue Index for MS.

Effect sizes varied across studies, as did the parameters examined within each study. The mean effect size was the largest for the association between REM sleep onset latency (ie, the time between sleep onset and initiation of REM sleep) and fatigue (r = 0.42), though this effect size was based on only two studies, and the association requires further investigation. “Shorter REM sleep onset latency has been associated with depression and narcolepsy,” both of which are more common in people with MS than in the general population, Dr. Bhattarai said. Subjective insomnia (r = 0.36) and objective sleep-related movement (r = 0.34) also yielded moderate effect sizes. “The shorter the REM sleep onset latency and the more subjective complaints that individuals have about their sleep, the greater the level of fatigue people with MS reported,” she said. “The more sleep-related movement that people have, the greater their level of MS-related fatigue.”

Potential to Inform Treatment Approach

The association between fatigue and objective sleep-disordered breathing was not statistically significant. Subjective sleep-disordered breathing, objective nocturnal arousals, sleep efficiency, sleep onset latency, and sleep duration had weak effect sizes. These problems are common and require treatment, however, Dr. Bhattarai said.

“When treating patients with MS who are experiencing MS-related fatigue, interventions geared toward improving patients’ perceived sleep quality and addressing MS symptoms that might disrupt sleep (eg, nocturia and periodic leg movements) may offer an avenue for improving fatigue,” said Dr. Bhattarai. “However, these effects remain to be shown in a randomized controlled trial.”

—Jake Remaly

Click here to read the supplement.

Click here to read the supplement.

Click here to read the supplement.

Click here to read the supplement.

Click here to read the supplement.

Click here to read the supplement.

Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).

• Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
• Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
• Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
• The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
• The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.

Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.

Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).

• Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
• Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
• Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
• The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
• The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.

Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.

Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).

• Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
• Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
• Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
• The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
• The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.

Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.

Neuropsychological testing may help differentiate epileptic seizures from psychogenic nonepileptic seizures (PNES) according to a study that evaluated data from 72 patients with epilepsy and 33 patients with PNES.

• In the past, psychometric testing has been shown to have limited utility in differentiating PNES from epileptic seizures.
• The new research suggests that multivariate assessment using several psychological tests is more effective in making the differential diagnosis.
• Using logistic regression, investigators found that a combination of 7 neuropsychological tests accurately classified about 85% of patients.
• The researchers acknowledged that video-EEG monitoring remains the gold standard for separating PNES from epileptic seizures but suggest that a standardized battery of neuropsychological tests may improve the clinical decision-making process.

Tyson BT, Baker S, Greenacre M, et al. Differentiating epilepsy from psychogenic nonepileptic seizures using neuropsychological test data. Epilepsy Behav. 2018;87:39-45.

Neuropsychological testing may help differentiate epileptic seizures from psychogenic nonepileptic seizures (PNES) according to a study that evaluated data from 72 patients with epilepsy and 33 patients with PNES.

• In the past, psychometric testing has been shown to have limited utility in differentiating PNES from epileptic seizures.
• The new research suggests that multivariate assessment using several psychological tests is more effective in making the differential diagnosis.
• Using logistic regression, investigators found that a combination of 7 neuropsychological tests accurately classified about 85% of patients.
• The researchers acknowledged that video-EEG monitoring remains the gold standard for separating PNES from epileptic seizures but suggest that a standardized battery of neuropsychological tests may improve the clinical decision-making process.

Tyson BT, Baker S, Greenacre M, et al. Differentiating epilepsy from psychogenic nonepileptic seizures using neuropsychological test data. Epilepsy Behav. 2018;87:39-45.

Neuropsychological testing may help differentiate epileptic seizures from psychogenic nonepileptic seizures (PNES) according to a study that evaluated data from 72 patients with epilepsy and 33 patients with PNES.

• In the past, psychometric testing has been shown to have limited utility in differentiating PNES from epileptic seizures.
• The new research suggests that multivariate assessment using several psychological tests is more effective in making the differential diagnosis.
• Using logistic regression, investigators found that a combination of 7 neuropsychological tests accurately classified about 85% of patients.
• The researchers acknowledged that video-EEG monitoring remains the gold standard for separating PNES from epileptic seizures but suggest that a standardized battery of neuropsychological tests may improve the clinical decision-making process.

Tyson BT, Baker S, Greenacre M, et al. Differentiating epilepsy from psychogenic nonepileptic seizures using neuropsychological test data. Epilepsy Behav. 2018;87:39-45.

Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.

• The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
• As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
• These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
•  ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
• QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.

McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009

Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.

• The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
• As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
• These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
•  ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
• QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.

McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009

Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.

• The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
• As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
• These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
•  ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
• QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.

McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

CHICAGO – When topical and oral medications alone don’t meet the needs of patients with atopic dermatitis, nonpharmaceutical options may benefit patients as adjunctive therapies, according to Peter A. Lio, MD, of Northwestern University, Chicago.

Cryotherapy and silk or silver fabrics have seen some good results, according to Dr. Lio, who cited his paper on nonpharmacologic therapies for atopic dermatitis. “There is another world of nonpharmacologic treatments that is perhaps nearly as extensive, though less well known, and likely underutilized by some clinicians.”

Dr. Lio described the treatment options for atopic dermatitis as the four points of a tetrahedron: anti-inflammatories, antibiotics, antipruritics, and moisturization.

Moisturization

“More moisturizer means less eczema,” Dr. Lio said. If patients find the moisturizer too cold, they can float the jar in a hot bath before applying it. On the flip side, patients who feel hotter or itchier when applying moisturizer may prefer keeping it in the refrigerator.

Evidence also supports balneotherapy and spa therapy, Dr. Lio said, though limited data exist to guide clinicians on the frequency or duration of baths or how soon to apply moisturizer after a bath. Research indicates benefit from bath and spa therapy lasting up to 3-6 months for mild to moderate eczema.

However, it’s hard to distinguish between the possible benefits of the spa therapy itself versus possible confounding benefits from what often accompanies spa therapy, such as climatotherapy (warm weather), heliotherapy (sunshine), and relaxation from being in a vacation setting.

It’s also unclear whether the minerals in the water matter. Balneotherapy studies have shown benefits from mineral-rich water, but research has shown no benefit from using a water softener to remove minerals from hard water. Furthermore, balneotherapy and spa therapy are expensive, time-consuming, and temporary.

Using wet wraps overnight is an easy and cheap alternative treatment. Dr. Lio recommended soaking onesies, pajamas, gloves, or socks (depending on the location of affected skin) in warm water and then wringing them out until slightly damp. The person puts on the damp clothes and dry pajamas, gloves, or socks over them, and ensures the room is warm enough before going to sleep.

Antibacterial agents

Some research has found an association between environmental Staphylococcus aureus and severe atopic dermatitis, suggesting a role for antibacterial agents, Dr. Lio said. Though the mechanism is unclear, a dilute bleach bath may help.

In a small, randomized, controlled trial of 31 children with moderate to severe eczema, all received oral antibiotics and were then randomized to receive either intranasal mupirocin and a dilute bleach bath twice weekly for 4 weeks or intranasal vaseline and a placebo bath. Those in the mupirocin/bleach bath group showed significant greater improvement, compared with the placebo group.

Yet other research has shown regular baths are superior to dilute bleach baths. It seems more likely that dilute bleach baths act more as an anti-inflammatory than an antibacterial agent, Dr. Lio said at the American Academy of Dermatology summer meeting.

Probiotics “is an area that’s teeming with potential, but right now we don’t really write a prescription for probiotics,” Dr. Lio told attendees. He shared a systematic review supporting probiotics’ use in pregnant mothers and newborns for preventing atopic dermatitis.

“I’m convinced there actually is significant evidence that, if you give expecting moms probiotics and then give it to the baby as soon as they come out, you can prevent or at least reduce the severity of the atopic dermatitis in a measurable portion of patients,” Dr. Lio said. However, he acknowledged other research suggesting probiotics simply delay onset of atopic dermatitis.

“The bacteria in our gut are quite different than [the bacteria] on our skin,” Dr. Lio said. Topical probiotics are under study, and “could be a nonpharmacologic adjunctive therapy.”

Silver and silver-coated clothing are anecdotally successful in select patients. One small study compared silk with topical steroids and implied good results, but most studies with silk remain small and underpowered. If patients want to try textile therapy, they can purchase small silk sleep sacs similar to a sleeping bag.

Silver-impregnated products display true antibacterial effects and do seem to improve atopic dermatitis and pruritus scores, he added, but there are downsides. “These products are pricey, and there’s an environmental issue when you wash these silver clothes and the silver hangs out in the water supply.”

Anti-inflammatories

Cryotherapy is a potential anti-inflammatory, nonpharmaceutical treatment worth exploring, Dr. Lio said. It’s not exactly clear how or why cryotherapy works, but there are several possibilities: Very cold air may increase the body’s antioxidative capacity or reduce the conduction velocity of peripheral nerves, or the cold may simply relieve itch through local or systemic anti-inflammatory effects. At the same time, treatment-related adverse effects from whole-body cryotherapy are a risk – particularly frostbite, Dr. Lio said.

Vitamin D “is a bit of a controversial topic,” Dr. Lio said. The research has gone up and down supporting its potential benefits, so Dr. Lio errs on the side of recommending it.

“It’s one of those things I just give to everybody,” he said, adding that the risk-benefit ratio makes vitamin D worth trying as adverse events are unlikely.

Antipruritics

Dr. Lio discussed the fourth point of the tetrahedron: anti-itching agents. Much has been tried – antihistamines, various topical agents (camphor, menthol, pramoxine), antidepressants, gabapentin, antipsychotics – but little has panned out from these medications.

One study found significantly less refractory uremic pruritus at 1 and 3 months after receiving acupressure.

Hypnosis and biofeedback appear worthwhile as well, perhaps via stress relief. Stress and sleep deprivation can worsen atopic dermatitis and slow healing of the skin barrier. Some research has found subjective and objective benefits from hypnosis.

Dr. Lio endorsed a “write it down” approach when managing atopic dermatitis patients. An Eczema Action Plan, clearly written and provided to the patient, can reduce anxiety levels and increase understanding of the treatment regimens and their risks and benefits.

Dr. Lio has received honoraria for speaking and/or consulting from Pierre-Fabre, L’Oreal, Regeneron, Sanofi Genzyme, Pfizer, Theraplex, Johnson & Johnson, AbbVie, Eli Lilly, Exeltis, Franklin BioScience, Galderma, Kiniksa Pharmaceuticals, Menlo Therapeutics, and Mission Pharmacal. He has also received research grants from Pierre-Fabre and AOBiome.

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.