Neurology

Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

msullivan@mdedge.com

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

msullivan@mdedge.com

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

msullivan@mdedge.com

Every year, thousands of us vow to “get in shape” by eating right and exercising. (Whether we keep that resolution is another story.) But while we view physical exercise as a way to lose or maintain weight, reduce stress, or even hone athletic skills, we seldom think about exercising one of the most important muscles in our body: the brain.

“What?” you say. “The brain is not like other muscles.” No, it’s not … and yet, it isn’t as different as we used to think. Historically (maybe histologically?), it was believed that if nerve cells in the adult brain were damaged or had died, they, unlike other cells in the body, were not replaced. Longstanding scientific belief was that while the brain compensated for damage by making new connections to undamaged nerve cells, it could not regenerate because it does not contain stem cells.¹

But since the late 1990s, scientists have been debunking the negative myths about our brains as we age. They are not as static and unable to change as we have been led to fear! In fact, in 1998, American and Swedish scientists demonstrated that adult humans can generate new brain cells.^1,2 Moreover, the brain does replicate neurons in the hippocampus, the area in our brains that is central to learning and memory. Neurons continue to grow and change beyond the first years of development and well into adulthood.

So learning (and teaching) movements to encourage the rebuilding of our neurons is key to keeping our minds sharp. In his work, Ratey found that “our physical movements can directly influence our ability to learn, think, and remember.”³ He also tells us that exercise enhances circulation to the brain, “priming it for improved function, including mental health as well as cognitive ability.”⁴

No, you can’t put your brain on a treadmill to get, and help keep, it “in shape.” But you can do something to maintain mental sharpness and delay decline in mental agility. And these exercises don’t require a health club membership or special equipment. They can be done anytime, anywhere … and no one knows you are doing them!

I’m talking about neurobics, a term coined to describe exercises that keep us mentally fit.⁵ The purpose of these activities is to work our brains in nonroutine or unexpected ways, using all of our senses to experience, or re-experience, a common activity.

Not sure what that means? Here are some examples:

Spend time in a new environment. Go to a different park or a new store. Travel, by the way, seems to slow age-related mental decline.

Continue to: Smell new odors in the morning

Smell new odors in the morning. Have new scents, like a bottle of mint extract, ready to smell first thing in the morning, to “wake up” your brain.

Take a shower with your eyes closed. Other senses become more active when you cannot see, and a shower engages several.

Try brushing your teeth with your nondominant hand. This may be difficult for some of us—and it definitely requires full attention the first time you try it!

Learn to read braille. This is a tough one, but learning to read with your fingers definitely involves one of your senses in a new context. Or, you could try learning American Sign Language, which also uses your fingers to communicate.

Respond to a situation differently. Catch yourself in a normal, unconscious response to a situation, and choose to respond in an alternate (and preferably better) way.

Continue to: Find a new route to work

Find a new route to work. It doesn’t have to be longer, just different. You may even find a faster way to work once you break your routine.

Act confidently. In a situation you are unsure about, choose to act confidently. You’ll notice that your mind gets very active once you adopt the assumption that you will know what to do.

Distinguish coins using only your sense of touch. This brain exercise can be used to kill time while waiting for an appointment. If you really want a challenge, see if you can distinguish paper currency denominations by touch.

Leave the lights off in the house. Get around your home by memory and feel. This certainly fully engages your attention—but be careful, of course!

If you give neurobics a try, let me know what you think! Or if you have other tips for staying mentally “fit,” please share them. I can be reached at npeditor@mdedge.com. And thank you to my friend Gail, who suggested this topic to me!

Every year, thousands of us vow to “get in shape” by eating right and exercising. (Whether we keep that resolution is another story.) But while we view physical exercise as a way to lose or maintain weight, reduce stress, or even hone athletic skills, we seldom think about exercising one of the most important muscles in our body: the brain.

“What?” you say. “The brain is not like other muscles.” No, it’s not … and yet, it isn’t as different as we used to think. Historically (maybe histologically?), it was believed that if nerve cells in the adult brain were damaged or had died, they, unlike other cells in the body, were not replaced. Longstanding scientific belief was that while the brain compensated for damage by making new connections to undamaged nerve cells, it could not regenerate because it does not contain stem cells.¹

But since the late 1990s, scientists have been debunking the negative myths about our brains as we age. They are not as static and unable to change as we have been led to fear! In fact, in 1998, American and Swedish scientists demonstrated that adult humans can generate new brain cells.^1,2 Moreover, the brain does replicate neurons in the hippocampus, the area in our brains that is central to learning and memory. Neurons continue to grow and change beyond the first years of development and well into adulthood.

So learning (and teaching) movements to encourage the rebuilding of our neurons is key to keeping our minds sharp. In his work, Ratey found that “our physical movements can directly influence our ability to learn, think, and remember.”³ He also tells us that exercise enhances circulation to the brain, “priming it for improved function, including mental health as well as cognitive ability.”⁴

No, you can’t put your brain on a treadmill to get, and help keep, it “in shape.” But you can do something to maintain mental sharpness and delay decline in mental agility. And these exercises don’t require a health club membership or special equipment. They can be done anytime, anywhere … and no one knows you are doing them!

I’m talking about neurobics, a term coined to describe exercises that keep us mentally fit.⁵ The purpose of these activities is to work our brains in nonroutine or unexpected ways, using all of our senses to experience, or re-experience, a common activity.

Not sure what that means? Here are some examples:

Spend time in a new environment. Go to a different park or a new store. Travel, by the way, seems to slow age-related mental decline.

Continue to: Smell new odors in the morning

Smell new odors in the morning. Have new scents, like a bottle of mint extract, ready to smell first thing in the morning, to “wake up” your brain.

Take a shower with your eyes closed. Other senses become more active when you cannot see, and a shower engages several.

Try brushing your teeth with your nondominant hand. This may be difficult for some of us—and it definitely requires full attention the first time you try it!

Learn to read braille. This is a tough one, but learning to read with your fingers definitely involves one of your senses in a new context. Or, you could try learning American Sign Language, which also uses your fingers to communicate.

Respond to a situation differently. Catch yourself in a normal, unconscious response to a situation, and choose to respond in an alternate (and preferably better) way.

Continue to: Find a new route to work

Find a new route to work. It doesn’t have to be longer, just different. You may even find a faster way to work once you break your routine.

Act confidently. In a situation you are unsure about, choose to act confidently. You’ll notice that your mind gets very active once you adopt the assumption that you will know what to do.

Distinguish coins using only your sense of touch. This brain exercise can be used to kill time while waiting for an appointment. If you really want a challenge, see if you can distinguish paper currency denominations by touch.

Leave the lights off in the house. Get around your home by memory and feel. This certainly fully engages your attention—but be careful, of course!

If you give neurobics a try, let me know what you think! Or if you have other tips for staying mentally “fit,” please share them. I can be reached at npeditor@mdedge.com. And thank you to my friend Gail, who suggested this topic to me!

Every year, thousands of us vow to “get in shape” by eating right and exercising. (Whether we keep that resolution is another story.) But while we view physical exercise as a way to lose or maintain weight, reduce stress, or even hone athletic skills, we seldom think about exercising one of the most important muscles in our body: the brain.

“What?” you say. “The brain is not like other muscles.” No, it’s not … and yet, it isn’t as different as we used to think. Historically (maybe histologically?), it was believed that if nerve cells in the adult brain were damaged or had died, they, unlike other cells in the body, were not replaced. Longstanding scientific belief was that while the brain compensated for damage by making new connections to undamaged nerve cells, it could not regenerate because it does not contain stem cells.¹

But since the late 1990s, scientists have been debunking the negative myths about our brains as we age. They are not as static and unable to change as we have been led to fear! In fact, in 1998, American and Swedish scientists demonstrated that adult humans can generate new brain cells.^1,2 Moreover, the brain does replicate neurons in the hippocampus, the area in our brains that is central to learning and memory. Neurons continue to grow and change beyond the first years of development and well into adulthood.

So learning (and teaching) movements to encourage the rebuilding of our neurons is key to keeping our minds sharp. In his work, Ratey found that “our physical movements can directly influence our ability to learn, think, and remember.”³ He also tells us that exercise enhances circulation to the brain, “priming it for improved function, including mental health as well as cognitive ability.”⁴

No, you can’t put your brain on a treadmill to get, and help keep, it “in shape.” But you can do something to maintain mental sharpness and delay decline in mental agility. And these exercises don’t require a health club membership or special equipment. They can be done anytime, anywhere … and no one knows you are doing them!

I’m talking about neurobics, a term coined to describe exercises that keep us mentally fit.⁵ The purpose of these activities is to work our brains in nonroutine or unexpected ways, using all of our senses to experience, or re-experience, a common activity.

Not sure what that means? Here are some examples:

Spend time in a new environment. Go to a different park or a new store. Travel, by the way, seems to slow age-related mental decline.

Continue to: Smell new odors in the morning

Smell new odors in the morning. Have new scents, like a bottle of mint extract, ready to smell first thing in the morning, to “wake up” your brain.

Take a shower with your eyes closed. Other senses become more active when you cannot see, and a shower engages several.

Try brushing your teeth with your nondominant hand. This may be difficult for some of us—and it definitely requires full attention the first time you try it!

Learn to read braille. This is a tough one, but learning to read with your fingers definitely involves one of your senses in a new context. Or, you could try learning American Sign Language, which also uses your fingers to communicate.

Respond to a situation differently. Catch yourself in a normal, unconscious response to a situation, and choose to respond in an alternate (and preferably better) way.

Continue to: Find a new route to work

Find a new route to work. It doesn’t have to be longer, just different. You may even find a faster way to work once you break your routine.

Act confidently. In a situation you are unsure about, choose to act confidently. You’ll notice that your mind gets very active once you adopt the assumption that you will know what to do.

Distinguish coins using only your sense of touch. This brain exercise can be used to kill time while waiting for an appointment. If you really want a challenge, see if you can distinguish paper currency denominations by touch.

Leave the lights off in the house. Get around your home by memory and feel. This certainly fully engages your attention—but be careful, of course!

If you give neurobics a try, let me know what you think! Or if you have other tips for staying mentally “fit,” please share them. I can be reached at npeditor@mdedge.com. And thank you to my friend Gail, who suggested this topic to me!

Vice Admiral Jerome M. Adams, MD, MPH, is the 20th Surgeon General of the United States, a post created in 1871.

Dr. Adams holds degrees in biochemistry and psychology from the University of Maryland, Baltimore County; a master’s degree in public health from the University of California, Berkeley; and a medical degree from the Indiana University, Indianapolis. He is a board-certified anesthesiologist and associate clinical professor of anesthesia at Indiana University.

At the 2018 Executive Advisory Board meeting of the Doctors Company, Richard E. Anderson, MD, FACP, chairman and chief executive officer of the Doctors Company, spoke with Dr. Adams about the opioid epidemic’s enormous impact on communities and health services in the United States.

Dr. Anderson: Dr. Adams, you’ve been busy since taking over as Surgeon General of the United States. What are some of the key challenges that you’re facing in this office?

Dr. Adams: You know, there are many challenges facing our country, but it boils down to a lack of wellness. We know that only 10% of health is due to health care, 20% of health is genetics, and the rest is a combination of behavior and environment.

My motto is “better health through better partnerships,” because I firmly believe that if we break out of our silos and reach across the traditional barriers that have been put up by funding, by reimbursement, and by infrastructure, then we can ultimately achieve wellness in our communities.

You asked what I’ve been focused on as Surgeon General. Well, I’m focused on three main areas right now.

No. 1 is the opioid epidemic. It is a scourge across our country. A person dies every 12½ minutes from an opioid overdose and that’s far too many. Especially when we know that many of those deaths can be prevented.

Another area I’m focused on is demonstrating the link between community health and economic prosperity. We want folks to invest in health because we know that not only will it achieve better health for individuals and communities but it will create a more prosperous nation, also.

And finally, I’m raising awareness about the links between our nation’s health and our safety and security – particularly our national security. Unfortunately, 7 out of 10 young people between the ages of 18 and 24 years old in our country are ineligible for military service. That’s because they can’t pass the physical, they can’t meet the educational requirements, or they have a criminal record.

So, our nation’s poor health is not just a matter of diabetes or heart disease 20 or 30 years down the road. We are literally a less-safe country right now because we’re an unhealthy country.
 

Dr. Anderson: Regarding the opioid epidemic, what are some of the programs that are available today that you find effective? What would you like to see us do as a nation to respond to the epidemic?

Dr. Adams: Recently, I was at a hospital in Alaska where they have implemented a neonatal abstinence syndrome protocol and program that is being looked at around the country – and others are attempting to replicate it.

We know that if you keep mom and baby together, baby does better, mom does better, hospital stays are shorter, costs go down, and you’re keeping that family unit intact. This prevents future problems for both the baby and the mother. That’s just one small example.

I’m also very happy to see that the prescribing of opioids is going down 20%-25% across the country. And there are even larger decreases in the military and veteran communities. That’s really a testament to doctors and the medical profession finally waking up. And I say this as a physician myself, as an anesthesiologist, as someone who is involved in acute and chronic pain management.

Four out of five people with substance use disorder say they started with a prescription opioid. Many physicians will say, “Those aren’t my patients,” but unfortunately when we look at the PDMP [prescription drug monitoring program] data across the country we do a poor job of predicting who is and who isn’t going to divert. It may not be your patient, but it could be their son or the babysitter who is diverting those overprescribed opioids.

One thing that I really think we need to lean into as health care practitioners is providing medication-assisted treatment, or MAT. We know that the gold standard for treatment and recovery is medication-assisted treatment of some form. But we also know it’s not nearly available enough and that there are barriers on the federal and state levels.

We need you to continue to talk to your congressional representatives and let them know which barriers you perceive because the data waiver comes directly from Congress.

Still, any ER can prescribe up to 3 days of MAT to someone. I’d much rather have our ER doctors putting patients on MAT and then connecting them to treatment, than sending them back out into the arms of a drug dealer after they put them into acute withdrawal with naloxone.

We also have too many pregnant women who want help but can’t find any treatment because no one out there will take care of pregnant moms. We need folks to step up to the plate and get that data waiver in our ob/gyn and primary care sectors.

Ultimately, we need hospitals and health care leaders to create an environment that makes providers feel comfortable providing that service by giving them the training and the support to be able to do it.

We also need to make sure we’re co-prescribing naloxone for those who are at risk for opioid overdose.
 

Dr. Anderson: Just so we are clear, are you in favor of regular prescribing of naloxone, along with prescriptions for opioids? Is that correct?

Dr. Adams: I issued the first Surgeon General’s advisory from more than 10 years earlier this year to help folks understand that over half of our opioid overdoses occur in a home setting. We all know that an anoxic brain injury occurs in 4-5 minutes. We also know that most ambulances and first responders aren’t going to show up in 4-5 minutes.

If we want to make a dent in this overdose epidemic, we need everyone to consider themselves a first responder. We need to look at it the same as we look at CPR; we need everyone carrying naloxone. That was one of the big pushes from my Surgeon General’s advisory.

How can providers help? Well, they can coprescribe naloxone to folks on high morphine milligram equivalents (MME) who are at risk. If grandma has naloxone at home and her grandson overdoses in the garage, then at least it’s in the same house. Naloxone is not the treatment for the opioid epidemic. But we can’t get someone who is dead into treatment.

I have no illusions that simply making naloxone available is going to turn the tide, but it certainly is an important part of it.
 

Dr. Anderson: From your unique viewpoint, how much progress do you see in relation to the opioid epidemic? Do you think we’re approaching an inflection point, or do you think there’s a long way to go before this starts to turn around?

Dr. Adams: When I talk about the opioid epidemic, I have two angles. No.1, I want to raise awareness about the opioid epidemic – the severity of it, and how everyone can lean into it in their own way. Whether it’s community citizens, providers, law enforcement, the business community, whomever.

But in addition to raising awareness, I want to instill hope.

I was in Huntington, West Virginia, just a few weeks ago at the epicenter of the opioid epidemic. They’ve been able to turn their opioid overdose rates around by providing peer recovery coaches to individuals and making sure naloxone is available throughout the community. You save the life and then you connect them to care.

We know that the folks who are at highest risk for overdose deaths are the ones who just overdosed. They come out of the ER where we’ve watched them for a few hours and then we send them right back out into the arms of the drug dealer to do exactly what we know they will do medically because we’ve thrown them into withdrawal and they try to get their next fix.

If we can partner with law enforcement, then we can turn our opioid overdose rates around.

A story of recovery that I want to share with you is about a guy named Jonathan, who I met when I was in Rhode Island.

Jonathan overdosed, but his roommate had access to naloxone, which he administered. Jonathan was taken to the ER and then connected with a peer recovery coach. He is now in recovery and has actually become a peer recovery coach himself. Saving this one life will now enable us to save many more.

Yet we still prescribe more than 80% of the world’s opioids to less than 5% of the world’s population. So, we still have an overprescribing epidemic, but we’ve surpassed the inflection point there. Prescribing is coming down.

But another part of this epidemic was that we squeezed the balloon in one place and, as prescribing opioids went down, lots of people switched over to heroin. That’s when we really first started to see overdose rates go up.

Well, it’s important for folks to know that, through law enforcement, through partnerships with the public health community, through an increase in syringe service programs, and through other touch points, heroin use is now going down in most places.

Unfortunately, now we’re seeing the third wave of the epidemic, and that’s fentanyl and carfentanil.






 

Vice Admiral Jerome M. Adams, MD, MPH, is the 20th Surgeon General of the United States, a post created in 1871.

Dr. Adams holds degrees in biochemistry and psychology from the University of Maryland, Baltimore County; a master’s degree in public health from the University of California, Berkeley; and a medical degree from the Indiana University, Indianapolis. He is a board-certified anesthesiologist and associate clinical professor of anesthesia at Indiana University.

At the 2018 Executive Advisory Board meeting of the Doctors Company, Richard E. Anderson, MD, FACP, chairman and chief executive officer of the Doctors Company, spoke with Dr. Adams about the opioid epidemic’s enormous impact on communities and health services in the United States.

Dr. Anderson: Dr. Adams, you’ve been busy since taking over as Surgeon General of the United States. What are some of the key challenges that you’re facing in this office?

Dr. Adams: You know, there are many challenges facing our country, but it boils down to a lack of wellness. We know that only 10% of health is due to health care, 20% of health is genetics, and the rest is a combination of behavior and environment.

My motto is “better health through better partnerships,” because I firmly believe that if we break out of our silos and reach across the traditional barriers that have been put up by funding, by reimbursement, and by infrastructure, then we can ultimately achieve wellness in our communities.

You asked what I’ve been focused on as Surgeon General. Well, I’m focused on three main areas right now.

No. 1 is the opioid epidemic. It is a scourge across our country. A person dies every 12½ minutes from an opioid overdose and that’s far too many. Especially when we know that many of those deaths can be prevented.

Another area I’m focused on is demonstrating the link between community health and economic prosperity. We want folks to invest in health because we know that not only will it achieve better health for individuals and communities but it will create a more prosperous nation, also.

And finally, I’m raising awareness about the links between our nation’s health and our safety and security – particularly our national security. Unfortunately, 7 out of 10 young people between the ages of 18 and 24 years old in our country are ineligible for military service. That’s because they can’t pass the physical, they can’t meet the educational requirements, or they have a criminal record.

So, our nation’s poor health is not just a matter of diabetes or heart disease 20 or 30 years down the road. We are literally a less-safe country right now because we’re an unhealthy country.
 

Dr. Anderson: Regarding the opioid epidemic, what are some of the programs that are available today that you find effective? What would you like to see us do as a nation to respond to the epidemic?

Dr. Adams: Recently, I was at a hospital in Alaska where they have implemented a neonatal abstinence syndrome protocol and program that is being looked at around the country – and others are attempting to replicate it.

We know that if you keep mom and baby together, baby does better, mom does better, hospital stays are shorter, costs go down, and you’re keeping that family unit intact. This prevents future problems for both the baby and the mother. That’s just one small example.

I’m also very happy to see that the prescribing of opioids is going down 20%-25% across the country. And there are even larger decreases in the military and veteran communities. That’s really a testament to doctors and the medical profession finally waking up. And I say this as a physician myself, as an anesthesiologist, as someone who is involved in acute and chronic pain management.

Four out of five people with substance use disorder say they started with a prescription opioid. Many physicians will say, “Those aren’t my patients,” but unfortunately when we look at the PDMP [prescription drug monitoring program] data across the country we do a poor job of predicting who is and who isn’t going to divert. It may not be your patient, but it could be their son or the babysitter who is diverting those overprescribed opioids.

One thing that I really think we need to lean into as health care practitioners is providing medication-assisted treatment, or MAT. We know that the gold standard for treatment and recovery is medication-assisted treatment of some form. But we also know it’s not nearly available enough and that there are barriers on the federal and state levels.

We need you to continue to talk to your congressional representatives and let them know which barriers you perceive because the data waiver comes directly from Congress.

Still, any ER can prescribe up to 3 days of MAT to someone. I’d much rather have our ER doctors putting patients on MAT and then connecting them to treatment, than sending them back out into the arms of a drug dealer after they put them into acute withdrawal with naloxone.

We also have too many pregnant women who want help but can’t find any treatment because no one out there will take care of pregnant moms. We need folks to step up to the plate and get that data waiver in our ob/gyn and primary care sectors.

Ultimately, we need hospitals and health care leaders to create an environment that makes providers feel comfortable providing that service by giving them the training and the support to be able to do it.

We also need to make sure we’re co-prescribing naloxone for those who are at risk for opioid overdose.
 

Dr. Anderson: Just so we are clear, are you in favor of regular prescribing of naloxone, along with prescriptions for opioids? Is that correct?

Dr. Adams: I issued the first Surgeon General’s advisory from more than 10 years earlier this year to help folks understand that over half of our opioid overdoses occur in a home setting. We all know that an anoxic brain injury occurs in 4-5 minutes. We also know that most ambulances and first responders aren’t going to show up in 4-5 minutes.

If we want to make a dent in this overdose epidemic, we need everyone to consider themselves a first responder. We need to look at it the same as we look at CPR; we need everyone carrying naloxone. That was one of the big pushes from my Surgeon General’s advisory.

How can providers help? Well, they can coprescribe naloxone to folks on high morphine milligram equivalents (MME) who are at risk. If grandma has naloxone at home and her grandson overdoses in the garage, then at least it’s in the same house. Naloxone is not the treatment for the opioid epidemic. But we can’t get someone who is dead into treatment.

I have no illusions that simply making naloxone available is going to turn the tide, but it certainly is an important part of it.
 

Dr. Anderson: From your unique viewpoint, how much progress do you see in relation to the opioid epidemic? Do you think we’re approaching an inflection point, or do you think there’s a long way to go before this starts to turn around?

Dr. Adams: When I talk about the opioid epidemic, I have two angles. No.1, I want to raise awareness about the opioid epidemic – the severity of it, and how everyone can lean into it in their own way. Whether it’s community citizens, providers, law enforcement, the business community, whomever.

But in addition to raising awareness, I want to instill hope.

I was in Huntington, West Virginia, just a few weeks ago at the epicenter of the opioid epidemic. They’ve been able to turn their opioid overdose rates around by providing peer recovery coaches to individuals and making sure naloxone is available throughout the community. You save the life and then you connect them to care.

We know that the folks who are at highest risk for overdose deaths are the ones who just overdosed. They come out of the ER where we’ve watched them for a few hours and then we send them right back out into the arms of the drug dealer to do exactly what we know they will do medically because we’ve thrown them into withdrawal and they try to get their next fix.

If we can partner with law enforcement, then we can turn our opioid overdose rates around.

A story of recovery that I want to share with you is about a guy named Jonathan, who I met when I was in Rhode Island.

Jonathan overdosed, but his roommate had access to naloxone, which he administered. Jonathan was taken to the ER and then connected with a peer recovery coach. He is now in recovery and has actually become a peer recovery coach himself. Saving this one life will now enable us to save many more.

Yet we still prescribe more than 80% of the world’s opioids to less than 5% of the world’s population. So, we still have an overprescribing epidemic, but we’ve surpassed the inflection point there. Prescribing is coming down.

But another part of this epidemic was that we squeezed the balloon in one place and, as prescribing opioids went down, lots of people switched over to heroin. That’s when we really first started to see overdose rates go up.

Well, it’s important for folks to know that, through law enforcement, through partnerships with the public health community, through an increase in syringe service programs, and through other touch points, heroin use is now going down in most places.

Unfortunately, now we’re seeing the third wave of the epidemic, and that’s fentanyl and carfentanil.






 

Vice Admiral Jerome M. Adams, MD, MPH, is the 20th Surgeon General of the United States, a post created in 1871.

Dr. Adams holds degrees in biochemistry and psychology from the University of Maryland, Baltimore County; a master’s degree in public health from the University of California, Berkeley; and a medical degree from the Indiana University, Indianapolis. He is a board-certified anesthesiologist and associate clinical professor of anesthesia at Indiana University.

At the 2018 Executive Advisory Board meeting of the Doctors Company, Richard E. Anderson, MD, FACP, chairman and chief executive officer of the Doctors Company, spoke with Dr. Adams about the opioid epidemic’s enormous impact on communities and health services in the United States.

Dr. Anderson: Dr. Adams, you’ve been busy since taking over as Surgeon General of the United States. What are some of the key challenges that you’re facing in this office?

Dr. Adams: You know, there are many challenges facing our country, but it boils down to a lack of wellness. We know that only 10% of health is due to health care, 20% of health is genetics, and the rest is a combination of behavior and environment.

My motto is “better health through better partnerships,” because I firmly believe that if we break out of our silos and reach across the traditional barriers that have been put up by funding, by reimbursement, and by infrastructure, then we can ultimately achieve wellness in our communities.

You asked what I’ve been focused on as Surgeon General. Well, I’m focused on three main areas right now.

No. 1 is the opioid epidemic. It is a scourge across our country. A person dies every 12½ minutes from an opioid overdose and that’s far too many. Especially when we know that many of those deaths can be prevented.

Another area I’m focused on is demonstrating the link between community health and economic prosperity. We want folks to invest in health because we know that not only will it achieve better health for individuals and communities but it will create a more prosperous nation, also.

And finally, I’m raising awareness about the links between our nation’s health and our safety and security – particularly our national security. Unfortunately, 7 out of 10 young people between the ages of 18 and 24 years old in our country are ineligible for military service. That’s because they can’t pass the physical, they can’t meet the educational requirements, or they have a criminal record.

So, our nation’s poor health is not just a matter of diabetes or heart disease 20 or 30 years down the road. We are literally a less-safe country right now because we’re an unhealthy country.
 

Dr. Anderson: Regarding the opioid epidemic, what are some of the programs that are available today that you find effective? What would you like to see us do as a nation to respond to the epidemic?

Dr. Adams: Recently, I was at a hospital in Alaska where they have implemented a neonatal abstinence syndrome protocol and program that is being looked at around the country – and others are attempting to replicate it.

We know that if you keep mom and baby together, baby does better, mom does better, hospital stays are shorter, costs go down, and you’re keeping that family unit intact. This prevents future problems for both the baby and the mother. That’s just one small example.

I’m also very happy to see that the prescribing of opioids is going down 20%-25% across the country. And there are even larger decreases in the military and veteran communities. That’s really a testament to doctors and the medical profession finally waking up. And I say this as a physician myself, as an anesthesiologist, as someone who is involved in acute and chronic pain management.

Four out of five people with substance use disorder say they started with a prescription opioid. Many physicians will say, “Those aren’t my patients,” but unfortunately when we look at the PDMP [prescription drug monitoring program] data across the country we do a poor job of predicting who is and who isn’t going to divert. It may not be your patient, but it could be their son or the babysitter who is diverting those overprescribed opioids.

One thing that I really think we need to lean into as health care practitioners is providing medication-assisted treatment, or MAT. We know that the gold standard for treatment and recovery is medication-assisted treatment of some form. But we also know it’s not nearly available enough and that there are barriers on the federal and state levels.

We need you to continue to talk to your congressional representatives and let them know which barriers you perceive because the data waiver comes directly from Congress.

Still, any ER can prescribe up to 3 days of MAT to someone. I’d much rather have our ER doctors putting patients on MAT and then connecting them to treatment, than sending them back out into the arms of a drug dealer after they put them into acute withdrawal with naloxone.

We also have too many pregnant women who want help but can’t find any treatment because no one out there will take care of pregnant moms. We need folks to step up to the plate and get that data waiver in our ob/gyn and primary care sectors.

Ultimately, we need hospitals and health care leaders to create an environment that makes providers feel comfortable providing that service by giving them the training and the support to be able to do it.

We also need to make sure we’re co-prescribing naloxone for those who are at risk for opioid overdose.
 

Dr. Anderson: Just so we are clear, are you in favor of regular prescribing of naloxone, along with prescriptions for opioids? Is that correct?

Dr. Adams: I issued the first Surgeon General’s advisory from more than 10 years earlier this year to help folks understand that over half of our opioid overdoses occur in a home setting. We all know that an anoxic brain injury occurs in 4-5 minutes. We also know that most ambulances and first responders aren’t going to show up in 4-5 minutes.

If we want to make a dent in this overdose epidemic, we need everyone to consider themselves a first responder. We need to look at it the same as we look at CPR; we need everyone carrying naloxone. That was one of the big pushes from my Surgeon General’s advisory.

How can providers help? Well, they can coprescribe naloxone to folks on high morphine milligram equivalents (MME) who are at risk. If grandma has naloxone at home and her grandson overdoses in the garage, then at least it’s in the same house. Naloxone is not the treatment for the opioid epidemic. But we can’t get someone who is dead into treatment.

I have no illusions that simply making naloxone available is going to turn the tide, but it certainly is an important part of it.
 

Dr. Anderson: From your unique viewpoint, how much progress do you see in relation to the opioid epidemic? Do you think we’re approaching an inflection point, or do you think there’s a long way to go before this starts to turn around?

Dr. Adams: When I talk about the opioid epidemic, I have two angles. No.1, I want to raise awareness about the opioid epidemic – the severity of it, and how everyone can lean into it in their own way. Whether it’s community citizens, providers, law enforcement, the business community, whomever.

But in addition to raising awareness, I want to instill hope.

I was in Huntington, West Virginia, just a few weeks ago at the epicenter of the opioid epidemic. They’ve been able to turn their opioid overdose rates around by providing peer recovery coaches to individuals and making sure naloxone is available throughout the community. You save the life and then you connect them to care.

We know that the folks who are at highest risk for overdose deaths are the ones who just overdosed. They come out of the ER where we’ve watched them for a few hours and then we send them right back out into the arms of the drug dealer to do exactly what we know they will do medically because we’ve thrown them into withdrawal and they try to get their next fix.

If we can partner with law enforcement, then we can turn our opioid overdose rates around.

A story of recovery that I want to share with you is about a guy named Jonathan, who I met when I was in Rhode Island.

Jonathan overdosed, but his roommate had access to naloxone, which he administered. Jonathan was taken to the ER and then connected with a peer recovery coach. He is now in recovery and has actually become a peer recovery coach himself. Saving this one life will now enable us to save many more.

Yet we still prescribe more than 80% of the world’s opioids to less than 5% of the world’s population. So, we still have an overprescribing epidemic, but we’ve surpassed the inflection point there. Prescribing is coming down.

But another part of this epidemic was that we squeezed the balloon in one place and, as prescribing opioids went down, lots of people switched over to heroin. That’s when we really first started to see overdose rates go up.

Well, it’s important for folks to know that, through law enforcement, through partnerships with the public health community, through an increase in syringe service programs, and through other touch points, heroin use is now going down in most places.

Unfortunately, now we’re seeing the third wave of the epidemic, and that’s fentanyl and carfentanil.






 

Civilian patients with mild traumatic brain injury (TBI) who are black, have psychiatric history or lower education, or whose injury was caused by assault might be at greater risk of developing posttraumatic stress disorder or major depression, a longitudinal study suggests.

Stockdevil/Thinkstock

“Our findings may have implications for surveillance and treatment of mental disorders after TBI,” wrote Murray B. Stein, MD, MPH, and his associates. The study was published Jan. 30 in JAMA Psychiatry.

The researchers looked at the risk factors for and prevalence of posttraumatic stress disorder (PTSD) and major depressive disorder among 1,155 patients. The patients were enrolled at 11 level 1 trauma centers across the United States after they were evaluated for mild TBI in emergency departments as part of a prospective study called Transforming Research and Clinical Knowledge in Traumatic Brain Injury, or TRACK-TBI. The comparison group was 230 patients with nonhead orthopedic trauma injuries, wrote Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego, and his associates.

They found that each additional year of education was associated with a significant 11% reduction in the risk of developing PTSD after mild TBI (P = .005). Also, black patients had a greater than fivefold higher risk of PTSD (P less than.001) than that of individuals who were not black.

Among patients with a history of mental illness and those who had experienced their injury as a result of assault or violence – as opposed to a motor vehicle accident or fall, for example – both had a greater than threefold higher risk of developing PTSD (odds ratio, 3.57 and 3.43 respectively). A prior TBI was nonsignificantly associated with an increased risk of developing PTSD.

Lower education duration, being black, or a history of mental illness also were all significantly associated with an increased risk of developing major depressive disorder after mild TBI.

However, duration of lost consciousness or posttraumatic amnesia, evidence of brain injury on CT, or hospitalization did not predict an increased risk of PTSD or major depression.

“Although MDD and PTSD are prevalent after TBI, little is known about which patients are at risk for developing them,” Dr. Stein and his associates wrote.

Noting that having a prior mental health problem was an “exceptionally strong” risk factor for PTSD and MDD after TBI, the authors said this could represent continuation or exacerbation of the prior mental health issue, or the triggering of a new episode in a person with a past history who had recovered.

“However, in either case this finding underscores the importance of clinicians being aware of the mental health history of their patients with [mild TBI], as this information is central to expectations regarding both short-term and long-term outcome,” they wrote.

Dr. Stein and his associates cited as a limitation their reliance on patient or family report. In addition, they said, the elevated risk for mental disorders among black individuals after mild TBI, which was independent of socioeconomic status or cause of injury, was not understood. “Unmeasured covariates may be part of the explanation; this is a topic needing further study,” they wrote.

The study was supported by the National Institutes of Health, the U.S. Department of Defense, Abbott Laboratories, and One Mind. Four authors declared consultancies, advisory board positions, speaking fees, and shares or stock options with the pharmaceutical and private industry. Two authors declared grants from the study sponsors.

SOURCE: Stein MB et al. JAMA Psychiatry. 2019. Jan 30. doi: 10.1001/jamapsychiatry.2018.4288.

Civilian patients with mild traumatic brain injury (TBI) who are black, have psychiatric history or lower education, or whose injury was caused by assault might be at greater risk of developing posttraumatic stress disorder or major depression, a longitudinal study suggests.

Stockdevil/Thinkstock

“Our findings may have implications for surveillance and treatment of mental disorders after TBI,” wrote Murray B. Stein, MD, MPH, and his associates. The study was published Jan. 30 in JAMA Psychiatry.

The researchers looked at the risk factors for and prevalence of posttraumatic stress disorder (PTSD) and major depressive disorder among 1,155 patients. The patients were enrolled at 11 level 1 trauma centers across the United States after they were evaluated for mild TBI in emergency departments as part of a prospective study called Transforming Research and Clinical Knowledge in Traumatic Brain Injury, or TRACK-TBI. The comparison group was 230 patients with nonhead orthopedic trauma injuries, wrote Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego, and his associates.

They found that each additional year of education was associated with a significant 11% reduction in the risk of developing PTSD after mild TBI (P = .005). Also, black patients had a greater than fivefold higher risk of PTSD (P less than.001) than that of individuals who were not black.

Among patients with a history of mental illness and those who had experienced their injury as a result of assault or violence – as opposed to a motor vehicle accident or fall, for example – both had a greater than threefold higher risk of developing PTSD (odds ratio, 3.57 and 3.43 respectively). A prior TBI was nonsignificantly associated with an increased risk of developing PTSD.

Lower education duration, being black, or a history of mental illness also were all significantly associated with an increased risk of developing major depressive disorder after mild TBI.

However, duration of lost consciousness or posttraumatic amnesia, evidence of brain injury on CT, or hospitalization did not predict an increased risk of PTSD or major depression.

“Although MDD and PTSD are prevalent after TBI, little is known about which patients are at risk for developing them,” Dr. Stein and his associates wrote.

Noting that having a prior mental health problem was an “exceptionally strong” risk factor for PTSD and MDD after TBI, the authors said this could represent continuation or exacerbation of the prior mental health issue, or the triggering of a new episode in a person with a past history who had recovered.

“However, in either case this finding underscores the importance of clinicians being aware of the mental health history of their patients with [mild TBI], as this information is central to expectations regarding both short-term and long-term outcome,” they wrote.

Dr. Stein and his associates cited as a limitation their reliance on patient or family report. In addition, they said, the elevated risk for mental disorders among black individuals after mild TBI, which was independent of socioeconomic status or cause of injury, was not understood. “Unmeasured covariates may be part of the explanation; this is a topic needing further study,” they wrote.

The study was supported by the National Institutes of Health, the U.S. Department of Defense, Abbott Laboratories, and One Mind. Four authors declared consultancies, advisory board positions, speaking fees, and shares or stock options with the pharmaceutical and private industry. Two authors declared grants from the study sponsors.

SOURCE: Stein MB et al. JAMA Psychiatry. 2019. Jan 30. doi: 10.1001/jamapsychiatry.2018.4288.

Civilian patients with mild traumatic brain injury (TBI) who are black, have psychiatric history or lower education, or whose injury was caused by assault might be at greater risk of developing posttraumatic stress disorder or major depression, a longitudinal study suggests.

Stockdevil/Thinkstock

“Our findings may have implications for surveillance and treatment of mental disorders after TBI,” wrote Murray B. Stein, MD, MPH, and his associates. The study was published Jan. 30 in JAMA Psychiatry.

The researchers looked at the risk factors for and prevalence of posttraumatic stress disorder (PTSD) and major depressive disorder among 1,155 patients. The patients were enrolled at 11 level 1 trauma centers across the United States after they were evaluated for mild TBI in emergency departments as part of a prospective study called Transforming Research and Clinical Knowledge in Traumatic Brain Injury, or TRACK-TBI. The comparison group was 230 patients with nonhead orthopedic trauma injuries, wrote Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego, and his associates.

They found that each additional year of education was associated with a significant 11% reduction in the risk of developing PTSD after mild TBI (P = .005). Also, black patients had a greater than fivefold higher risk of PTSD (P less than.001) than that of individuals who were not black.

Among patients with a history of mental illness and those who had experienced their injury as a result of assault or violence – as opposed to a motor vehicle accident or fall, for example – both had a greater than threefold higher risk of developing PTSD (odds ratio, 3.57 and 3.43 respectively). A prior TBI was nonsignificantly associated with an increased risk of developing PTSD.

Lower education duration, being black, or a history of mental illness also were all significantly associated with an increased risk of developing major depressive disorder after mild TBI.

However, duration of lost consciousness or posttraumatic amnesia, evidence of brain injury on CT, or hospitalization did not predict an increased risk of PTSD or major depression.

“Although MDD and PTSD are prevalent after TBI, little is known about which patients are at risk for developing them,” Dr. Stein and his associates wrote.

Noting that having a prior mental health problem was an “exceptionally strong” risk factor for PTSD and MDD after TBI, the authors said this could represent continuation or exacerbation of the prior mental health issue, or the triggering of a new episode in a person with a past history who had recovered.

“However, in either case this finding underscores the importance of clinicians being aware of the mental health history of their patients with [mild TBI], as this information is central to expectations regarding both short-term and long-term outcome,” they wrote.

Dr. Stein and his associates cited as a limitation their reliance on patient or family report. In addition, they said, the elevated risk for mental disorders among black individuals after mild TBI, which was independent of socioeconomic status or cause of injury, was not understood. “Unmeasured covariates may be part of the explanation; this is a topic needing further study,” they wrote.

The study was supported by the National Institutes of Health, the U.S. Department of Defense, Abbott Laboratories, and One Mind. Four authors declared consultancies, advisory board positions, speaking fees, and shares or stock options with the pharmaceutical and private industry. Two authors declared grants from the study sponsors.

SOURCE: Stein MB et al. JAMA Psychiatry. 2019. Jan 30. doi: 10.1001/jamapsychiatry.2018.4288.

One of the common symptoms described by postconcussion patients is that their heads feel a bit foggy. It may not be simply by chance that “foggy” is the best word to describe the atmosphere surrounding the entire field of concussion diagnosis and management.

KatarzynaBialasiewicz/Thinkstock

Back in the Dark Ages, when the diagnosis of concussion was a simpler binary call, the issue of management seldom created much discussion. If the patient lost consciousness or was amnesic, he (it was less frequently she) could return to activity when his headache was gone and he could remember what he was supposed to do when the quarterback called for a “Red 34, Drive Right Smash” play. That may have even been during the second half of the game in which he was injured.

As it became more widely understood that the diagnosis of concussion didn’t require loss of consciousness and that repeated concussions could have serious sequelae, management became a bit fuzzier. No one had thought much about the recuperative process. Into this vacuum came a wide variety of researchers and providers. Concussion management blossomed into a cottage industry, populated by neurologists, orthopedists, trainers, sports medicine specialists, and physical therapists. Not surprisingly, much of their advice was based on unproven assumptions, including the concept of “brain rest.”

It has taken time, but fortunately, folks with patience and wisdom have questioned these assumptions and begun collecting data. The result of these investigations and others has prompted the American Academy of Pediatrics to publish an updated set of guidelines on concussion management that includes the observation that extended school absence may slow the rehabilitation process (Pediatrics. 2018 Dec. doi: 10.1542/peds.2018-3074).

It is becoming clear that management of concussion can be rather complex and must be individualized to each patient. In my experience, the postconcussion period can unmask behavioral, cognitive, and emotional problems that were preexisting but had received little or no attention. For example, the trauma of the event may trigger anxiety about further injury or exacerbate depression that had been building for years. The student who “couldn’t do algebra” following a head injury may have had a lifelong learning disability that had gone unnoticed. The student athlete with prolonged postconcussion symptoms may indeed have another more serious problem. Hopefully, the new guidelines from the AAP will be a first step toward a more thoughtful and scientifically driven approach to concussion management.

It would be nice if that approach could filter down to the management of the more common but less dramatic pediatric injuries. There is hope. Choosing Wisely – a patient/parent–targeted initiative by the American Board of Internal Medicine Foundation in cooperation with the AAP – points out that, although half of the pediatric head injury patients seen in emergency departments received CT scan, only a third of those studies were indicated. Parents are encouraged to learn more about the risks of CT scans and question the physician when one is recommended.

But, doctors’ habits and old wives’ tales die slowly. I hope that you no longer recommend that parents keep their children awake after a head injury, or wake them every hour to check their pupils. Those counterproductive recommendations make about as much sense as staying out of the swimming pool for an hour after eating a chocolate chip cookie.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

One of the common symptoms described by postconcussion patients is that their heads feel a bit foggy. It may not be simply by chance that “foggy” is the best word to describe the atmosphere surrounding the entire field of concussion diagnosis and management.

KatarzynaBialasiewicz/Thinkstock

Back in the Dark Ages, when the diagnosis of concussion was a simpler binary call, the issue of management seldom created much discussion. If the patient lost consciousness or was amnesic, he (it was less frequently she) could return to activity when his headache was gone and he could remember what he was supposed to do when the quarterback called for a “Red 34, Drive Right Smash” play. That may have even been during the second half of the game in which he was injured.

As it became more widely understood that the diagnosis of concussion didn’t require loss of consciousness and that repeated concussions could have serious sequelae, management became a bit fuzzier. No one had thought much about the recuperative process. Into this vacuum came a wide variety of researchers and providers. Concussion management blossomed into a cottage industry, populated by neurologists, orthopedists, trainers, sports medicine specialists, and physical therapists. Not surprisingly, much of their advice was based on unproven assumptions, including the concept of “brain rest.”

It has taken time, but fortunately, folks with patience and wisdom have questioned these assumptions and begun collecting data. The result of these investigations and others has prompted the American Academy of Pediatrics to publish an updated set of guidelines on concussion management that includes the observation that extended school absence may slow the rehabilitation process (Pediatrics. 2018 Dec. doi: 10.1542/peds.2018-3074).

It is becoming clear that management of concussion can be rather complex and must be individualized to each patient. In my experience, the postconcussion period can unmask behavioral, cognitive, and emotional problems that were preexisting but had received little or no attention. For example, the trauma of the event may trigger anxiety about further injury or exacerbate depression that had been building for years. The student who “couldn’t do algebra” following a head injury may have had a lifelong learning disability that had gone unnoticed. The student athlete with prolonged postconcussion symptoms may indeed have another more serious problem. Hopefully, the new guidelines from the AAP will be a first step toward a more thoughtful and scientifically driven approach to concussion management.

It would be nice if that approach could filter down to the management of the more common but less dramatic pediatric injuries. There is hope. Choosing Wisely – a patient/parent–targeted initiative by the American Board of Internal Medicine Foundation in cooperation with the AAP – points out that, although half of the pediatric head injury patients seen in emergency departments received CT scan, only a third of those studies were indicated. Parents are encouraged to learn more about the risks of CT scans and question the physician when one is recommended.

But, doctors’ habits and old wives’ tales die slowly. I hope that you no longer recommend that parents keep their children awake after a head injury, or wake them every hour to check their pupils. Those counterproductive recommendations make about as much sense as staying out of the swimming pool for an hour after eating a chocolate chip cookie.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

One of the common symptoms described by postconcussion patients is that their heads feel a bit foggy. It may not be simply by chance that “foggy” is the best word to describe the atmosphere surrounding the entire field of concussion diagnosis and management.

KatarzynaBialasiewicz/Thinkstock

Back in the Dark Ages, when the diagnosis of concussion was a simpler binary call, the issue of management seldom created much discussion. If the patient lost consciousness or was amnesic, he (it was less frequently she) could return to activity when his headache was gone and he could remember what he was supposed to do when the quarterback called for a “Red 34, Drive Right Smash” play. That may have even been during the second half of the game in which he was injured.

As it became more widely understood that the diagnosis of concussion didn’t require loss of consciousness and that repeated concussions could have serious sequelae, management became a bit fuzzier. No one had thought much about the recuperative process. Into this vacuum came a wide variety of researchers and providers. Concussion management blossomed into a cottage industry, populated by neurologists, orthopedists, trainers, sports medicine specialists, and physical therapists. Not surprisingly, much of their advice was based on unproven assumptions, including the concept of “brain rest.”

It has taken time, but fortunately, folks with patience and wisdom have questioned these assumptions and begun collecting data. The result of these investigations and others has prompted the American Academy of Pediatrics to publish an updated set of guidelines on concussion management that includes the observation that extended school absence may slow the rehabilitation process (Pediatrics. 2018 Dec. doi: 10.1542/peds.2018-3074).

It is becoming clear that management of concussion can be rather complex and must be individualized to each patient. In my experience, the postconcussion period can unmask behavioral, cognitive, and emotional problems that were preexisting but had received little or no attention. For example, the trauma of the event may trigger anxiety about further injury or exacerbate depression that had been building for years. The student who “couldn’t do algebra” following a head injury may have had a lifelong learning disability that had gone unnoticed. The student athlete with prolonged postconcussion symptoms may indeed have another more serious problem. Hopefully, the new guidelines from the AAP will be a first step toward a more thoughtful and scientifically driven approach to concussion management.

It would be nice if that approach could filter down to the management of the more common but less dramatic pediatric injuries. There is hope. Choosing Wisely – a patient/parent–targeted initiative by the American Board of Internal Medicine Foundation in cooperation with the AAP – points out that, although half of the pediatric head injury patients seen in emergency departments received CT scan, only a third of those studies were indicated. Parents are encouraged to learn more about the risks of CT scans and question the physician when one is recommended.

But, doctors’ habits and old wives’ tales die slowly. I hope that you no longer recommend that parents keep their children awake after a head injury, or wake them every hour to check their pupils. Those counterproductive recommendations make about as much sense as staying out of the swimming pool for an hour after eating a chocolate chip cookie.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.

SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.

Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.

The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.

“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”

The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.

“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”

NIA director Richard J. Hodes, MD, agreed.

“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”

SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.

Michelle Sullivan/MDedge News

The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.

Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.

The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.

Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.

As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”

msullivan@mdedge.com

SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.

A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.

SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.

Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.

The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.

“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”

The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.

“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”

NIA director Richard J. Hodes, MD, agreed.

“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”

SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.

Michelle Sullivan/MDedge News

The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.

Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.

The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.

Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.

As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”

msullivan@mdedge.com

SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.

A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.

SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.

Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.

The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.

“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”

The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.

“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”

NIA director Richard J. Hodes, MD, agreed.

“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”

SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.

Michelle Sullivan/MDedge News

The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.

Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.

The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.

Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.

As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”

msullivan@mdedge.com

SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.

Age, symptom severity, and serum glucose do not influence the benefit of endovascular thrombectomy for patients with stroke, according to research published online ahead of print Jan. 28 in JAMA Neurology. The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.

The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).

A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.

The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.

The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.

“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”

The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.

The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.

egreb@mdedge.com

SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.

Age, symptom severity, and serum glucose do not influence the benefit of endovascular thrombectomy for patients with stroke, according to research published online ahead of print Jan. 28 in JAMA Neurology. The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.

The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).

A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.

The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.

The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.

“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”

The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.

The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.

egreb@mdedge.com

SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.

Age, symptom severity, and serum glucose do not influence the benefit of endovascular thrombectomy for patients with stroke, according to research published online ahead of print Jan. 28 in JAMA Neurology. The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.

The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).

A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.

The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.

The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.

“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”

The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.

The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.

egreb@mdedge.com

SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.

Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.

“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.

Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.

To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.

Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.

Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).

The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.

“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”

Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.

The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.

The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.

The authors disclosed research fellowships and support from foundations and federal agencies.

jremaly@mdedge.com

SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.

Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.

“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.

Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.

To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.

Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.

Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).

The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.

“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”

Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.

The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.

The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.

The authors disclosed research fellowships and support from foundations and federal agencies.

jremaly@mdedge.com

SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.

Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.

“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.

Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.

To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.

Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.

Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).

The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.

“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”

Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.

The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.

The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.

The authors disclosed research fellowships and support from foundations and federal agencies.

jremaly@mdedge.com

SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.