CHICAGO – Nearly two-thirds of rheumatoid arthritis patients who achieved remission or low disease activity on tocilizumab plus low-dose prednisone were able to taper off prednisone treatment while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.

Mitchel L. Zoler/MDedge.com

The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.

But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.

These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.

Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.

“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.

The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.

A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.

The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.

[email protected]

SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.

CHICAGO – Nearly two-thirds of rheumatoid arthritis patients who achieved remission or low disease activity on tocilizumab plus low-dose prednisone were able to taper off prednisone treatment while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.

Mitchel L. Zoler/MDedge.com

The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.

But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.

These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.

Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.

“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.

The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.

A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.

The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.

[email protected]

SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.

CHICAGO – Nearly two-thirds of rheumatoid arthritis patients who achieved remission or low disease activity on tocilizumab plus low-dose prednisone were able to taper off prednisone treatment while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.

Mitchel L. Zoler/MDedge.com

The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.

But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.

These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.

Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.

“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.

The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.

A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.

The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.

[email protected]

SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.

The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.

©Karen Mower/iStockphoto

Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.

The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”

Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.

Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.

Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.

As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.

Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.

Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.

“It just made me go crazy,” she said. “I was all messed up in my head.”

The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.

In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.

“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”

Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.

“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”

Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.

In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.

“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.

Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.

“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”

Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.

Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.

Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.

Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.

The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.

There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.

“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.

The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.

©Karen Mower/iStockphoto

Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.

The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”

Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.

Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.

Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.

As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.

Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.

Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.

“It just made me go crazy,” she said. “I was all messed up in my head.”

The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.

In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.

“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”

Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.

“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”

Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.

In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.

“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.

Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.

“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”

Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.

Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.

Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.

Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.

The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.

There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.

“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.

The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.

©Karen Mower/iStockphoto

Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.

The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”

Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.

Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.

Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.

As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.

Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.

Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.

“It just made me go crazy,” she said. “I was all messed up in my head.”

The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.

In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.

“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”

Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.

“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”

Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.

In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.

“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.

Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.

“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”

Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.

Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.

Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.

Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.

The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.

There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.

“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Click to Read the Supplement.

Based on material presented at the 2018 Metabolic & Endocrine Disease Summit (MEDS), this CME supplement to Clinician Reviews provides an overview of evidence and best practices for individualizing and intensifying antihyperglycemic therapy using current basal insulin options to achieve patient-centered goals in individuals with type 2 diabetes mellitus (T2DM). Physician assistants, nurse practitioners and nurses will have the opportunity to complete pre- and post-assessment questions to earn a maximum of 1.5 free CME/CE credits.
 
Dr. Vanita Aroda and Ms. Davida Kruger walk readers through the following learning objectives: 

• Explain the role/usage of ultralong-acting basal insulins for addressing the underlying pathophysiology of T2DM
• Compare ultralong-acting and other basal insulins regarding therapeutic characteristics, including pharmacokinetic/pharmacodynamic profiles, efficacy, safety, and dosing
• Develop patient-centered treatment regimens that include ultralong-acting insulins to minimize barriers to successful use of basal insulin therapy
  
   

Click to Read the Supplement.

Click to Read the Supplement.

Based on material presented at the 2018 Metabolic & Endocrine Disease Summit (MEDS), this CME supplement to Clinician Reviews provides an overview of evidence and best practices for individualizing and intensifying antihyperglycemic therapy using current basal insulin options to achieve patient-centered goals in individuals with type 2 diabetes mellitus (T2DM). Physician assistants, nurse practitioners and nurses will have the opportunity to complete pre- and post-assessment questions to earn a maximum of 1.5 free CME/CE credits.
 
Dr. Vanita Aroda and Ms. Davida Kruger walk readers through the following learning objectives: 

• Explain the role/usage of ultralong-acting basal insulins for addressing the underlying pathophysiology of T2DM
• Compare ultralong-acting and other basal insulins regarding therapeutic characteristics, including pharmacokinetic/pharmacodynamic profiles, efficacy, safety, and dosing
• Develop patient-centered treatment regimens that include ultralong-acting insulins to minimize barriers to successful use of basal insulin therapy
  
   

Click to Read the Supplement.

Click to Read the Supplement.

Based on material presented at the 2018 Metabolic & Endocrine Disease Summit (MEDS), this CME supplement to Clinician Reviews provides an overview of evidence and best practices for individualizing and intensifying antihyperglycemic therapy using current basal insulin options to achieve patient-centered goals in individuals with type 2 diabetes mellitus (T2DM). Physician assistants, nurse practitioners and nurses will have the opportunity to complete pre- and post-assessment questions to earn a maximum of 1.5 free CME/CE credits.
 
Dr. Vanita Aroda and Ms. Davida Kruger walk readers through the following learning objectives: 

• Explain the role/usage of ultralong-acting basal insulins for addressing the underlying pathophysiology of T2DM
• Compare ultralong-acting and other basal insulins regarding therapeutic characteristics, including pharmacokinetic/pharmacodynamic profiles, efficacy, safety, and dosing
• Develop patient-centered treatment regimens that include ultralong-acting insulins to minimize barriers to successful use of basal insulin therapy
  
   

Click to Read the Supplement.

NASHVILLE – Women who successfully maintained weight loss burned a greater proportion of their daily calories through physical activity than did controls with either normal or high body mass, but the same effect wasn’t seen in men, according to new analysis of a small study.

Kari Oakes/MDedge News

Physical activity is a key component in successful maintenance of weight loss, but differential effects of physical activity between men and women had not been well explored, Ann Caldwell, PhD, said in an interview at Obesity Week 2018, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Dr. Caldwell and her colleagues at the University of Colorado Anschutz Medical Campus, Aurora, conducted a secondary analysis of case-control data of individuals with healthy weight, overweight, or obesity, and those who had successfully maintained weight loss. They compared total daily energy expenditure (TDEE) and physical activity energy expenditure (PAEE), looking at men and women in all three groups separately.

The study included 20 women and 5 men who had successfully maintained a weight loss of at least 13.6 kg for at least 1 year. These were matched with 20 women and 7 men with a body mass index within the healthy range, as controls for the weight loss maintainers at their post–weight loss BMI.

Another group of 22 women and 6 men with BMIs in the overweight or obese category served as controls for the weight loss maintainers at their pre–weight loss BMI.

For all participants, TDEE was measured using the doubly labeled water method for 7 days. This method tracks elimination of a set quantity of ingested water made up of two uncommon isotopes (hydrogen-2 and oxygen-18) to measure energy expenditure. Since the oxygen is lost both as water and carbon dioxide as a result of metabolism, the presence of less oxygen-18 over time indicates a higher total energy expenditure.

Indirect calorimetry was used to measure resting energy expenditure (REE), and energy expenditure related to physical activity was calculated by subtracting REE and a 10% fraction of TDEE (to account for the thermic effect of feeding) from total TDEE.

“There were significant sex-group interactions for TDEE, PAEE, and PAEE/TEE,” said Dr. Caldwell. She explained that the cutoff for statistical significance for the investigators’ analysis was set at P = .1, since sample sizes were so small for men.

For women who were weight-loss maintainers, both PAEE and PAEE/TDEE ratios were higher than for the female healthy-BMI and high-BMI control participants: PAEE was 822 kcal/day for the maintainers, 536 kcal/day for the healthy-BMI, and 669 kcal/day for the high-BMI controls (P less than .01 for both comparisons).

Dr. Caldwell and her colleagues saw no difference when comparing the PAEE/TDEE ratio for women in each of the control groups.

For men, by contrast, PAEE was highest for those with healthy BMIs, at 815 kcal/day, and lowest for those in the high-BMI control group, at 506 kcal/day. Men who were weight loss maintainers fell in the middle, at 772 kcal/day of PAEE. The PAEE/TDEE ratio was significantly higher for both weight loss maintainers and normal-BMI participants than for the high-BMI participants (P less than .07).

“These cross-sectional data suggest potential sex differences in the importance of [physical activity] for successful weight loss maintenance that should be explored further with objective measures,” wrote Dr. Caldwell and her coauthors.

The investigators are planning further work that incorporates objective physical activity data via actigraphy, and that will include a larger sample of men. Through a prospective study that overcomes the limitation of the present study, they hope to develop a clearer picture of sex differences in weight loss maintenance.

The National Institutes of Health supported the study. Dr. Caldwell reported no relevant conflicts of interest.
 

[email protected]

SOURCE: Caldwell A et al. Obesity Week 2018, Abstract TP-3233.

NASHVILLE – Women who successfully maintained weight loss burned a greater proportion of their daily calories through physical activity than did controls with either normal or high body mass, but the same effect wasn’t seen in men, according to new analysis of a small study.

Kari Oakes/MDedge News

Physical activity is a key component in successful maintenance of weight loss, but differential effects of physical activity between men and women had not been well explored, Ann Caldwell, PhD, said in an interview at Obesity Week 2018, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Dr. Caldwell and her colleagues at the University of Colorado Anschutz Medical Campus, Aurora, conducted a secondary analysis of case-control data of individuals with healthy weight, overweight, or obesity, and those who had successfully maintained weight loss. They compared total daily energy expenditure (TDEE) and physical activity energy expenditure (PAEE), looking at men and women in all three groups separately.

The study included 20 women and 5 men who had successfully maintained a weight loss of at least 13.6 kg for at least 1 year. These were matched with 20 women and 7 men with a body mass index within the healthy range, as controls for the weight loss maintainers at their post–weight loss BMI.

Another group of 22 women and 6 men with BMIs in the overweight or obese category served as controls for the weight loss maintainers at their pre–weight loss BMI.

For all participants, TDEE was measured using the doubly labeled water method for 7 days. This method tracks elimination of a set quantity of ingested water made up of two uncommon isotopes (hydrogen-2 and oxygen-18) to measure energy expenditure. Since the oxygen is lost both as water and carbon dioxide as a result of metabolism, the presence of less oxygen-18 over time indicates a higher total energy expenditure.

Indirect calorimetry was used to measure resting energy expenditure (REE), and energy expenditure related to physical activity was calculated by subtracting REE and a 10% fraction of TDEE (to account for the thermic effect of feeding) from total TDEE.

“There were significant sex-group interactions for TDEE, PAEE, and PAEE/TEE,” said Dr. Caldwell. She explained that the cutoff for statistical significance for the investigators’ analysis was set at P = .1, since sample sizes were so small for men.

For women who were weight-loss maintainers, both PAEE and PAEE/TDEE ratios were higher than for the female healthy-BMI and high-BMI control participants: PAEE was 822 kcal/day for the maintainers, 536 kcal/day for the healthy-BMI, and 669 kcal/day for the high-BMI controls (P less than .01 for both comparisons).

Dr. Caldwell and her colleagues saw no difference when comparing the PAEE/TDEE ratio for women in each of the control groups.

For men, by contrast, PAEE was highest for those with healthy BMIs, at 815 kcal/day, and lowest for those in the high-BMI control group, at 506 kcal/day. Men who were weight loss maintainers fell in the middle, at 772 kcal/day of PAEE. The PAEE/TDEE ratio was significantly higher for both weight loss maintainers and normal-BMI participants than for the high-BMI participants (P less than .07).

“These cross-sectional data suggest potential sex differences in the importance of [physical activity] for successful weight loss maintenance that should be explored further with objective measures,” wrote Dr. Caldwell and her coauthors.

The investigators are planning further work that incorporates objective physical activity data via actigraphy, and that will include a larger sample of men. Through a prospective study that overcomes the limitation of the present study, they hope to develop a clearer picture of sex differences in weight loss maintenance.

The National Institutes of Health supported the study. Dr. Caldwell reported no relevant conflicts of interest.
 

[email protected]

SOURCE: Caldwell A et al. Obesity Week 2018, Abstract TP-3233.

NASHVILLE – Women who successfully maintained weight loss burned a greater proportion of their daily calories through physical activity than did controls with either normal or high body mass, but the same effect wasn’t seen in men, according to new analysis of a small study.

Kari Oakes/MDedge News

Physical activity is a key component in successful maintenance of weight loss, but differential effects of physical activity between men and women had not been well explored, Ann Caldwell, PhD, said in an interview at Obesity Week 2018, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Dr. Caldwell and her colleagues at the University of Colorado Anschutz Medical Campus, Aurora, conducted a secondary analysis of case-control data of individuals with healthy weight, overweight, or obesity, and those who had successfully maintained weight loss. They compared total daily energy expenditure (TDEE) and physical activity energy expenditure (PAEE), looking at men and women in all three groups separately.

The study included 20 women and 5 men who had successfully maintained a weight loss of at least 13.6 kg for at least 1 year. These were matched with 20 women and 7 men with a body mass index within the healthy range, as controls for the weight loss maintainers at their post–weight loss BMI.

Another group of 22 women and 6 men with BMIs in the overweight or obese category served as controls for the weight loss maintainers at their pre–weight loss BMI.

For all participants, TDEE was measured using the doubly labeled water method for 7 days. This method tracks elimination of a set quantity of ingested water made up of two uncommon isotopes (hydrogen-2 and oxygen-18) to measure energy expenditure. Since the oxygen is lost both as water and carbon dioxide as a result of metabolism, the presence of less oxygen-18 over time indicates a higher total energy expenditure.

Indirect calorimetry was used to measure resting energy expenditure (REE), and energy expenditure related to physical activity was calculated by subtracting REE and a 10% fraction of TDEE (to account for the thermic effect of feeding) from total TDEE.

“There were significant sex-group interactions for TDEE, PAEE, and PAEE/TEE,” said Dr. Caldwell. She explained that the cutoff for statistical significance for the investigators’ analysis was set at P = .1, since sample sizes were so small for men.

For women who were weight-loss maintainers, both PAEE and PAEE/TDEE ratios were higher than for the female healthy-BMI and high-BMI control participants: PAEE was 822 kcal/day for the maintainers, 536 kcal/day for the healthy-BMI, and 669 kcal/day for the high-BMI controls (P less than .01 for both comparisons).

Dr. Caldwell and her colleagues saw no difference when comparing the PAEE/TDEE ratio for women in each of the control groups.

For men, by contrast, PAEE was highest for those with healthy BMIs, at 815 kcal/day, and lowest for those in the high-BMI control group, at 506 kcal/day. Men who were weight loss maintainers fell in the middle, at 772 kcal/day of PAEE. The PAEE/TDEE ratio was significantly higher for both weight loss maintainers and normal-BMI participants than for the high-BMI participants (P less than .07).

“These cross-sectional data suggest potential sex differences in the importance of [physical activity] for successful weight loss maintenance that should be explored further with objective measures,” wrote Dr. Caldwell and her coauthors.

The investigators are planning further work that incorporates objective physical activity data via actigraphy, and that will include a larger sample of men. Through a prospective study that overcomes the limitation of the present study, they hope to develop a clearer picture of sex differences in weight loss maintenance.

The National Institutes of Health supported the study. Dr. Caldwell reported no relevant conflicts of interest.
 

[email protected]

SOURCE: Caldwell A et al. Obesity Week 2018, Abstract TP-3233.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.¹ Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.

Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.² Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.^3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.

Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.^5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.⁷ The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.

In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.

Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.⁴

As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at [email protected].

References

1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.

2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.

4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.

5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.

6. J Adolesc Health. 2016; 58(2)(supple):S1-2.

7. JAMA Pediatr. 2018 Nov;172(11):1020-8.

It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.¹ Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.

Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.² Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.^3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.

Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.^5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.⁷ The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.

In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.

Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.⁴

As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at [email protected].

References

1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.

2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.

4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.

5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.

6. J Adolesc Health. 2016; 58(2)(supple):S1-2.

7. JAMA Pediatr. 2018 Nov;172(11):1020-8.

It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.¹ Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.

Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.² Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.^3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.

Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.^5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.⁷ The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.

In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.

Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.⁴

As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at [email protected].

References

1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.

2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.

4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.

5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.

6. J Adolesc Health. 2016; 58(2)(supple):S1-2.

7. JAMA Pediatr. 2018 Nov;172(11):1020-8.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

[email protected]

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

[email protected]

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – In addition to the pain, motor and sensory impairments, and cognitive dysfunction that can stalk multiple sclerosis (MS) patients, for many, there’s also the challenge of an invisible, tough-to-quantify entity: fatigue.

©RusN/Thinkstock.com

“Approximately 80% of patients suffer from fatigue, so it’s an immense problem in MS. There’s no real clear relationship with disease severity,” Vincent de Groot, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “Despite what a lot of people think, there’s no clear or strong relationship between fatigue and the amount of physical activity people undertake daily,” he noted.

“Patients all know what we are talking about when we ask about fatigue,” but there are a variety of definitions of fatigue used in research, a fact that has limited progress in the field, said Dr. de Groot.

Primary fatigue is related to the pathophysiology of MS itself, while secondary fatigue can result from MS symptoms, such as poor sleep from spasms. Secondary fatigue can also be a side effect of MS medications; baclofen, used for spasticity, is a good example, said Dr. de Groot. “We must not underestimate how many problems these drugs can give people.”

What’s the mechanism by which MS causes primary fatigue? “The simple answer is that we do not know,” said Dr. de Groot, a physiatrist and researcher at Vrije University, Amsterdam.

Though immune-mediated fatigue had been proposed as a factor for patients with MS, Dr. de Groot said that his own lab’s work has not found any connection between fatigue levels and any immune-related biomarkers. “So I don’t think the immune hypothesis has a lot of evidence.”

Similarly, though there might be mechanistic reasons to suspect the hypothalamic-pituitary-adrenal (HPA) axis as a culprit for MS fatigue, no consistent association has been found between any markers for HPA axis disruption and fatigue ratings, Dr. de Groot said.

Newer theories center on MS-related disruptions in brain connectivity, with imaging studies now able to detect some of these disruptions in functional connectivity that correlate with fatigue. “Right now, I think this is the hypothesis to bet money on,” Dr. de Groot said.

Many factors come into play, including environmental and psychological factors, he said.

“What can we do to treat MS-related fatigue?” Though several drugs have been used, “if you carefully look at the systematic reviews, the evidence is very, very disappointing,” Dr. de Groot said. For both amantadine and modafinil, “there is no evidence that these drugs are effective,” he said, citing a systematic review and meta-analysis that found a pooled effect size of 0.07 (95% confidence interval, –0.22 to 0.37) for medications (Mult Scler Int. 2014 May; doi: 10.1155/2014/798285).

Only two trials have looked at multidisciplinary rehabilitation for MS-related fatigue, Dr. de Groot said. Two studies that looked at multidisciplinary strategies that pulled in a variety of disciplines to help develop tailored fatigue management strategies saw no between-group effect when the multidisciplinary intervention was compared with nurse-provided information or with non–fatigue-related rehabilitation.

In an effort to determine whether MS-related fatigue is truly refractory to treatment, Dr. de Groot said that he and his colleagues decided to take “three steps back” to look at the individual interventions that make up a multidisciplinary approach to tackling fatigue. “So, we looked at exercise therapy, energy conservation management, and cognitive-behavioral therapy,” beginning with a literature review, he said.

Members of his research group found that effect sizes ranged from small to moderate for the three approaches, but there were methodologic problems with many of the studies; in the case of cognitive-behavioral therapy (CBT), the effect size waned over time, Dr. de Groot said. A newer randomized, controlled trial showed a relatively robust effect size of 0.52 for Internet-delivered CBT, which may provide a promising and practical approach (J Neurol Neurosurg Psychiatry. 2018 Sep;89[9]:970-6. doi: 10.1136/jnnp-2017-317463).

Looking at fatigue and societal participation, Dr. de Groot and his colleagues examined what effect aerobic training, energy conservation management, and CBT had on the two outcome measures. The three interventions were studied in three stand-alone trials, he said.

Patients were assessed at baseline, and at 8, 16, 26, and 52 weeks. The assessments were performed by a blinded researcher and were the same across trials: For fatigue, researchers used the Checklist Individual Strength–fatigue (CIS20R-fatigue), and for societal participation, they administered the Impact on Participation and Autonomy (IPA).

Each trial included 90 patients, randomized 1:1 to receive high- or low-intensity treatment. Patients had to have MS with no exacerbations within the prior 6 months and an Expanded Disability Status Scale score of 6 or less. However, the included patients had severe fatigue, with a CIS20R-fatigue subscore of 35 or higher, and the fatigue could not be attributable to such secondary causes as infection, depression, or thyroid or sleep problems. Finally, patients could not have been treated for fatigue in the 3 months prior to enrollment.

Those in the high-intensity treatment group received 12 sessions focused on the particular intervention over 4 months, provided by an expert therapist. Each type of intervention had a treatment protocol that was followed over the 4 months. Patients receiving low-intensity treatment saw an MS-specialized nurse three times over 4 months.

The aerobic training intervention had patients performing high-intensity exercise on a cycle ergometer for 30 minutes, three times weekly for 16 weeks. In addition to the 12 supervised sessions, patients also completed 36 home-based sessions. The level of intensity for each patient was personalized based on their baseline cardiopulmonary exercise test, Dr. de Groot said.

At the end of 1 year, patients in the high-intensity group and those in the low-intensity group reported virtually the same fatigue scores. Though there was an initial drop in fatigue for those in the high-intensity group, compared with baseline and with the low-intensity participants, values on the CIS20R never dropped below 35, the “severe fatigue” cutoff.

And, Dr. de Groot said, there was no effect on societal participation or in other fatigue scores. In sum, the effect size was barely significant at –0.54 (95% CI, –1.00 to –0.06), with a number needed to treat of 9.

Adherence to attempting the workouts was fairly good for participants in the high-intensity group; 74% completed the sessions, with 71% doing so at the prescribed workload. The median rate of perceived exertion on a 1-20 scale was 14.

However, the thrice-weekly exercise bouts didn’t improve aerobic fitness parameters: Neither V0₂peak, V0₂peak adjusted for body mass, nor anaerobic threshold changed for those in the high-intensity group. Peak power did increase by 11.7 watts (P = .048).

Energy conservation education, whether delivered in high- or low-intensity format, had almost no effect on fatigue scores, with a number needed to treat of 158 – a figure that is “neither significant nor clinically meaningful,” Dr. de Groot said. Other fatigue scores and societal participation levels also went unchanged.

However, CBT delivered in a series of 10 modules to address various beliefs and coping mechanisms about MS, fatigue, pain, and activity regulation did have a positive effect on fatigue. Here, the effect size was –0.79 (95% CI, –1.26 to –0.32). The number needed to treat was 3, and CIS20R values did dip below the “severe fatigue” threshold during treatment. A similar effect, Dr. de Groot said, was seen for other fatigue and quality of life measures, though societal participation scores didn’t change. No significant improvement was seen for the low-intensity CBT group.

“Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect in the long term,” Dr. de Groot said. Still, “it’s currently the best treatment option,” he said.

The fact that patients reverted to their preintervention fatigue levels regardless of the intervention shows that effective treatment for MS-related fatigue should probably be ongoing, viewed more as a process than an occurrence, Dr. de Groot said.

To that end, Dr. de Groot and his colleagues are conducting a randomized, controlled trial that includes 166 MS patients with fatigue. The study has two arms: The first is a noninferiority trial comparing face-to-face CBT with e-learning delivery of the content, and the second looks at the efficacy of ongoing booster sessions after initial CBT.

An online database of randomized, controlled trials of rehabilitation for MS patients can be found at www.appeco.net.

The study was funded by Fonds NutsOhra, a private Dutch foundation. Dr. de Groot reported no relevant conflicts of interest.

[email protected]

SOURCE: de Groot V. Mult Scler. 2018;24(S2):83, Abstract 225.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.