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Vagus nerve stimulation for rheumatology? Maybe
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
The work is being led by SetPoint Medical, a small company in Valencia, Calif., just north of Los Angeles. Its vagus nerve stimulation (VNS) device, dubbed the microregulator, has been implanted in 14 patients with refractory rheumatoid arthritis (RA) in the company’s initial safety study.
The microregulator is a small lithium ion battery encased in an inert silastic pod; it’s surgically implanted to sit atop the vagus nerve in the left side of the neck, and delivers an electrical pulse at set intervals. Data from the 12-week, sham-controlled safety study is set to be unblinded in coming weeks. A pivotal trial also is in the works, perhaps to start in late 2019, according to rheumatologist and SetPoint’s Chief Medical Officer David Chernoff, MD.
Although SetPoint is ahead of the pack, it’s not alone. ElectroCore, a biotech company in Basking Ridge, N.J., has expressed interest in pursuing rheumatoid arthritis and Sjögren’s syndrome indications for its gammaCore device, a vagus nerve stimulator patients apply to the neck. It’s already on the market for migraines and cluster headaches.
Researchers recently reported a small decrease in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) results after 16 RA patients with flares used the device for 4 days (Ann Rheum Dis. 2018;77:1401. Abstract AB0481). In another recent open-label study, 15 women with Sjögren’s reported less fatigue while using the device for a month (Arthritis Rheumatol. 2017;69[suppl 10]: Abstract 563).
Meanwhile, The Feinstein Institute for Medical Research, based in Manhasset, N.Y., on Long Island, recently reported positive outcomes in 18 patients with systemic lupus erythematosus, using its own novel device, which stimulates the vagus nerve through the ear lobe. VNS was delivered for 5 minutes per day for 4 days (Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2652).
On day 5, patients who received VNS, versus sham patients in whom the device was not turned on, had a significant decrease in pain, fatigue, and joint scores. The investigators concluded that “additional studies evaluating this promising intervention and its potential mechanisms are warranted.”
“We are clearly ahead of everybody because we’ve already implanted people, but I think it’s good for the field if more people are chasing this. The more resources that are put into it, the more we can show that this approach actually works,” said SetPoint’s Dr. Chernoff.
The hope
In general, interest in VNS for rheumatology is being driven by the possibility that it may reduce proinflammatory cytokines, which opens the door for VNS as an alternative to biologics. The hope is that instead of going after tumor necrosis factor and other cytokines one at a time, VNS could be used to target a range of cytokines all at once, without the cost and side effects of biologics.
“It seems so dramatically different” from what rheumatologists have done in the past, “that our first instinct is to say ‘oh, that’s ridiculous,’ but the science behind it is actually not bad. There may indeed be something to this,” said rheumatologist Joel Kremer, MD, Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
Dr. Kremer reviewed SetPoint’s early scientific data after being asked by the company to participate in the safety study; he declined for logistical reasons.
He noted that “there are some strange interactions between the CNS and inflammatory disease.” When RA patients have a stroke, for instance, RA goes into remission on the side of their body affected by the stroke. “That’s been known for decades, but we really don’t understand what’s going on there,” Dr. Kremer said.
The evidence
Perhaps the strongest evidence to date for VNS as a cytokine blocker in rheumatology comes from an open-label, 12-week study, also conducted by SetPoint, in 17 patients with active RA despite methotrexate treatment; some had failed biologics (Proc Natl Acad Sci U S A. 2016 Jul 19;113[29]:8284-9. doi: 10.1073/pnas.160563511).
The microregulator wasn’t ready yet, so investigators implanted a VNS system commercially available for epilepsy and reprogrammed it to deliver a 60-second pulse once a day to the left cervical vagus nerve, which was increased after a month to four 60-second stimulations a day in nonresponders.
The investigators “observed that TNF production in cultured peripheral blood obtained ... on day 42 was significantly reduced from” 21 days before the study was started (TNF 2,900 pg/mL on day –21, versus 1,776 pg/mL on day 42; P less than .05).
When VNS was shut off, TNF production increased; when it was turned back on, it dropped. Interleukin 6 also fell significantly among responders. Overall, DAS28-CRP scores fell about 1.5 points on the 10-point scale from baseline to week 12.
Two-year outcomes were recently reported (Ann Rheum Dis. 2018;77:981-2. Abstract SAT0240). All 17 patients elected to continue treatment after the initial 12 weeks. Biologics were added in nine subjects (53%), because of no or limited response to VNS. Investigators were free to change the VNS dosing regimen, which varied during the study extension up to eight 60-second bursts a day. The roughly 1.5-point improvement in DAS28-CRP was maintained at 2 years.
“These long-term data suggest that bioelectronic therapy may be used as an alternative to, or in combination with, biological[s],” concluded Dr. Chernoff and other study team members.
Awaiting more data
When asked for comment, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, said “there certainly are neurotropic factors” at play in rheumatology, “so there’s sort of a potential reason why” VNS might work, “but we need to understand far more about its mechanism, and [remember] that open-label studies are not to be believed until” large, randomized, blinded, placebo-controlled studies are done.
Dr. Furst also is an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). He is in part-time practice in Los Angeles and Seattle.
If everything works out, however, “the vagus nerve may give us a much wider opportunity to block a host of cytokines; it may change the whole paradigm of how we manage rheumatoid arthritis. I think this is possibly a groundbreaking new therapeutic area, much in the way the biologics were” 20 years ago, said rheumatologist Norman B. Gaylis, MD.
Several of the 14 patients in SetPoint’s safety study were enrolled at Dr. Gaylis’s practice in Aventura, Fla., just north of Miami; he said he is eagerly awaiting for the results to be unblinded. If clinical response in that study and others correlates with a cytokine response, “that’s going to be big, and very significant” in the rheumatology community, he said.
SetPoint’s microregulator is charged wirelessly through a collar patients wear for a few minutes once a week. Dosing can also be adjusted through the collar with the help of a computer application.
The device wasn’t turned on in 4 of the 14 patients in the safety study, as a sham control, but shamming was problematic because patients can potentially feel VNS as a buzz or a change in their voice. To get around that potential confounder, both sham and treated patients were told they might or might not feel something during the study.
Implantation takes about an hour, and is much less complex than implanting currently available epilepsy VNS systems, which require implantation of both a power source on the chest wall and wire coils on the vagus nerve.
Cardiac concerns are the main safety issue with VNS, beyond the surgery itself. Cardiac monitoring was done in the safety study to “ensure that we did not cause things like bradycardia, heart block, syncope, etc.” Dr. Chernoff said. So far, they haven’t turned out to be a problem.
Dr. Furst and Dr. Kremer had no relevant disclosures. Dr. Gaylis was compensated by SetPoint for participating in the safety study; he is a consultant and investigator for Electrocore. Dr. Furst and Dr. Gaylis are members of the editorial advisory board for MDedge Rheumatology/Rheumatology News.
IV ketamine, intranasal esketamine likely to ‘happily coexist’
Dr. Steven Levine offers perspective on how the FDA approval will affect patients, practice
Q: Why is this a “banner day” for psychiatry?
A: This is truly the first new option for depression in 60 years. The selective serotonin reuptake inhibitors (SSRIs) developed in the mid-’80s were not truly new, not much different from the monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants. In fact, they work much like watered-down MAOIs. Esketamine works by a truly novel mechanism.
Even though it constitutes a relatively new treatment, ketamine is a very old medicine, and we probably know more about the pharmacology and mechanisms in depression than for the SSRIs.
The idea of SSRIs working by increasing levels of neurotransmitters like serotonin has never held water. We never really believed that, but for people who respond to them – and many are helped – what is really happening weeks to months down the line is that these drugs increase the plasticity of the brain. Depression, like other mental health conditions, disrupts connections between important brain regions, reducing the number, function, and quality of the connections, and we believe SSRIs improve these.
Ketamine does these same things by a different route and much, much more quickly.
Q: What is esketamine’s method of action, and how long will a dose last?
A: Ketamine and esketamine bind to and block glutamate N-methyl-D-aspartate (NMDA) receptors. This leads to the release of several chemical messengers, the result of which increases the production of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF), that play a key role in healing damaged connections in the brain. A single dose of esketamine would only be expected to relieve depression symptoms for days, up to a week or 2. Multiple doses over the first few weeks can extend the durability of response to several weeks and sometimes months.
It is not true for every patient, but some do have improvement within 2-4 hours that correlates with physiologic changes. Others can be later responders and require up to 6 exposures.
Q: The FDA approval requires those who administer the drug to complete special training and meet licensure requirements. Is this realistic for small practices?
A: Initially, not every psychiatrist will be able to offer esketamine, and I think it might be beyond the reach of small practices, and that’s probably okay. Enough people and enough centers will be able to offer it to meet the initial demand.
Q: Is esketamine “better” than ketamine infusions? With the approved drug available, will ketamine infusion clinics still have a place?
A: There are major pros with this. The FDA approval takes out of the gray area of off-label administration. It will most likely be covered by insurance now – a huge advantage that will put this in the reach of so many patients who haven’t been able to access this treatment.
I think that, because there are advantages and disadvantages for both IV ketamine and nasal esketamine, they will happily coexist for years to come. However, because nasal esketamine will likely be restricted to prescription by psychiatrists, it may have more impact on non-psychiatrist-led practices. In this way,
Dr. Steven Levine is the founder of Actify Neurotherapies, which operates nine clinics providing ketamine treatment for depression.
Dr. Steven Levine offers perspective on how the FDA approval will affect patients, practice
Dr. Steven Levine offers perspective on how the FDA approval will affect patients, practice
Q: Why is this a “banner day” for psychiatry?
A: This is truly the first new option for depression in 60 years. The selective serotonin reuptake inhibitors (SSRIs) developed in the mid-’80s were not truly new, not much different from the monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants. In fact, they work much like watered-down MAOIs. Esketamine works by a truly novel mechanism.
Even though it constitutes a relatively new treatment, ketamine is a very old medicine, and we probably know more about the pharmacology and mechanisms in depression than for the SSRIs.
The idea of SSRIs working by increasing levels of neurotransmitters like serotonin has never held water. We never really believed that, but for people who respond to them – and many are helped – what is really happening weeks to months down the line is that these drugs increase the plasticity of the brain. Depression, like other mental health conditions, disrupts connections between important brain regions, reducing the number, function, and quality of the connections, and we believe SSRIs improve these.
Ketamine does these same things by a different route and much, much more quickly.
Q: What is esketamine’s method of action, and how long will a dose last?
A: Ketamine and esketamine bind to and block glutamate N-methyl-D-aspartate (NMDA) receptors. This leads to the release of several chemical messengers, the result of which increases the production of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF), that play a key role in healing damaged connections in the brain. A single dose of esketamine would only be expected to relieve depression symptoms for days, up to a week or 2. Multiple doses over the first few weeks can extend the durability of response to several weeks and sometimes months.
It is not true for every patient, but some do have improvement within 2-4 hours that correlates with physiologic changes. Others can be later responders and require up to 6 exposures.
Q: The FDA approval requires those who administer the drug to complete special training and meet licensure requirements. Is this realistic for small practices?
A: Initially, not every psychiatrist will be able to offer esketamine, and I think it might be beyond the reach of small practices, and that’s probably okay. Enough people and enough centers will be able to offer it to meet the initial demand.
Q: Is esketamine “better” than ketamine infusions? With the approved drug available, will ketamine infusion clinics still have a place?
A: There are major pros with this. The FDA approval takes out of the gray area of off-label administration. It will most likely be covered by insurance now – a huge advantage that will put this in the reach of so many patients who haven’t been able to access this treatment.
I think that, because there are advantages and disadvantages for both IV ketamine and nasal esketamine, they will happily coexist for years to come. However, because nasal esketamine will likely be restricted to prescription by psychiatrists, it may have more impact on non-psychiatrist-led practices. In this way,
Dr. Steven Levine is the founder of Actify Neurotherapies, which operates nine clinics providing ketamine treatment for depression.
Q: Why is this a “banner day” for psychiatry?
A: This is truly the first new option for depression in 60 years. The selective serotonin reuptake inhibitors (SSRIs) developed in the mid-’80s were not truly new, not much different from the monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants. In fact, they work much like watered-down MAOIs. Esketamine works by a truly novel mechanism.
Even though it constitutes a relatively new treatment, ketamine is a very old medicine, and we probably know more about the pharmacology and mechanisms in depression than for the SSRIs.
The idea of SSRIs working by increasing levels of neurotransmitters like serotonin has never held water. We never really believed that, but for people who respond to them – and many are helped – what is really happening weeks to months down the line is that these drugs increase the plasticity of the brain. Depression, like other mental health conditions, disrupts connections between important brain regions, reducing the number, function, and quality of the connections, and we believe SSRIs improve these.
Ketamine does these same things by a different route and much, much more quickly.
Q: What is esketamine’s method of action, and how long will a dose last?
A: Ketamine and esketamine bind to and block glutamate N-methyl-D-aspartate (NMDA) receptors. This leads to the release of several chemical messengers, the result of which increases the production of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF), that play a key role in healing damaged connections in the brain. A single dose of esketamine would only be expected to relieve depression symptoms for days, up to a week or 2. Multiple doses over the first few weeks can extend the durability of response to several weeks and sometimes months.
It is not true for every patient, but some do have improvement within 2-4 hours that correlates with physiologic changes. Others can be later responders and require up to 6 exposures.
Q: The FDA approval requires those who administer the drug to complete special training and meet licensure requirements. Is this realistic for small practices?
A: Initially, not every psychiatrist will be able to offer esketamine, and I think it might be beyond the reach of small practices, and that’s probably okay. Enough people and enough centers will be able to offer it to meet the initial demand.
Q: Is esketamine “better” than ketamine infusions? With the approved drug available, will ketamine infusion clinics still have a place?
A: There are major pros with this. The FDA approval takes out of the gray area of off-label administration. It will most likely be covered by insurance now – a huge advantage that will put this in the reach of so many patients who haven’t been able to access this treatment.
I think that, because there are advantages and disadvantages for both IV ketamine and nasal esketamine, they will happily coexist for years to come. However, because nasal esketamine will likely be restricted to prescription by psychiatrists, it may have more impact on non-psychiatrist-led practices. In this way,
Dr. Steven Levine is the founder of Actify Neurotherapies, which operates nine clinics providing ketamine treatment for depression.
The Oscars of contact allergens
Multiple sclerosis prevalence estimates reach their highest point to date. ASCO issues a new guideline for early detection and management of colorectal cancer in average-risk patients. And food allergies at age 1 often disappear by age 6.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Multiple sclerosis prevalence estimates reach their highest point to date. ASCO issues a new guideline for early detection and management of colorectal cancer in average-risk patients. And food allergies at age 1 often disappear by age 6.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Multiple sclerosis prevalence estimates reach their highest point to date. ASCO issues a new guideline for early detection and management of colorectal cancer in average-risk patients. And food allergies at age 1 often disappear by age 6.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Deprescribing: Nicolas Badre
In this episode of the MDedge Psychcast, Dr. Lorenzo Norris speaks with Dr. Nicolas Badre about ways to approach reducing dosages or discontinuing medications that are not beneficial. Dr. Badre, who has written about “deprescribing,” is a forensic psychiatrist who holds teaching positions at the University of California San Diego, and the University of San Diego.
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In this episode of the MDedge Psychcast, Dr. Lorenzo Norris speaks with Dr. Nicolas Badre about ways to approach reducing dosages or discontinuing medications that are not beneficial. Dr. Badre, who has written about “deprescribing,” is a forensic psychiatrist who holds teaching positions at the University of California San Diego, and the University of San Diego.
Subscribe here:
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Apple Podcasts
Google Podcasts
Spotify
In this episode of the MDedge Psychcast, Dr. Lorenzo Norris speaks with Dr. Nicolas Badre about ways to approach reducing dosages or discontinuing medications that are not beneficial. Dr. Badre, who has written about “deprescribing,” is a forensic psychiatrist who holds teaching positions at the University of California San Diego, and the University of San Diego.
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FDA approves intranasal esketamine for refractory major depressive disorder
The spray (Spravato; Janssen Pharmaceuticals) will come in tamper-resistant prepackaged units of one, two, or three devices to deliver the prescribed doses of 28 mg, 56 mg, or 84 mg, respectively. To reduce the risk of diversion, misuse, or abuse, the drug will managed under an FDA Risk Evaluation and Management Strategy (REMS). It will only be available to prescribing clinicians who have undergone training on the risks of esketamine and the importance of monitoring patients after their dose is administered. Facilities licensed to dispense esketamine must have the ability to medically monitor patients for at least 2 hours after administration. Patients will self-administer the spray and will not be able to take any of it home.
The REMS will require both prescriber and the patient to both sign a Patient Enrollment Form clearly stating that patients understand the necessity of assisted transport to leave the health care facility and that there should be no driving or use of heavy machinery for the rest of the day on which they are treated.
A boxed warning on the label will note that patients are at risk for sedation and difficulty with attention, judgment, and thinking (dissociation); abuse and misuse; and suicidal thoughts and behaviors after administration of the drug.
Despite the FDA’s caveats, the approval of intranasal esketamine is seen as a substantial win for the psychiatric community, Tiffany Farchione, MD, acting director of the FDA division of psychiatry products, said in a statement. “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition.”
“Spravato has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies,” said Mathai Mammen, MD, PhD, global head of Janssen Research and Development.
The company “is working quickly to educate and certify treatment centers in accordance with the REMS so that health care providers can offer Spravato to appropriate patients,” according to a statement from Janssen. “Later this month, patients can visit www.SPRAVATO.com for a locater tool and to sign up to receive alerts when new treatment centers are available.”
Intranasal esketamine was evaluated in three short-term clinical trials and one longer-term maintenance-of-effect trial. One of the studies demonstrated a clinically significant effect in depression severity, in as little as 2 days for some patients. The two other short-term trials did not show significant benefit. However, in the maintenance study, patients in stable remission or with stable response who continued treatment with esketamine plus an oral antidepressant experienced a significantly longer time to relapse of depressive symptoms than patients on placebo spray plus an oral antidepressant. The most common side effects were disassociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders might be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine might impair attention, judgment, thinking, reaction speed, and motor skills. It may cause fetal harm; women of childbearing age should be on reliable contraception. Breastfeeding women should not use it.
.
I’m not surprised by the FDA decision, given the strong endorsement from the advisory committees in mid-February based on the drug’s benefit-to-risk evaluation. This is an important advance for our field, and the FDA approval will allow more patients who suffer from treatment-resistant depression to gain access to this medication.
To date, ketamine (not the intranasal esketamine spray) has been offered primarily on a fee-for-service basis or in the context of a clinical trial. I anticipate this treatment to receive broad insurance coverage, but this remains to be determined.
Dr. Sanjay J. Mathew is the Marjorie Bintliff Johnson and Raleigh White Johnson Jr. Vice Chair for Research and professor in the Menninger department of psychiatry & behavioral sciences at the Baylor College of Medicine. He also is affiliated with the Michael E. Debakey VA Medical Center in Houston. Dr. Mathew has served as a consultant for and has had research funded by Janssen Pharmaceuticals.
I’m not surprised by the FDA decision, given the strong endorsement from the advisory committees in mid-February based on the drug’s benefit-to-risk evaluation. This is an important advance for our field, and the FDA approval will allow more patients who suffer from treatment-resistant depression to gain access to this medication.
To date, ketamine (not the intranasal esketamine spray) has been offered primarily on a fee-for-service basis or in the context of a clinical trial. I anticipate this treatment to receive broad insurance coverage, but this remains to be determined.
Dr. Sanjay J. Mathew is the Marjorie Bintliff Johnson and Raleigh White Johnson Jr. Vice Chair for Research and professor in the Menninger department of psychiatry & behavioral sciences at the Baylor College of Medicine. He also is affiliated with the Michael E. Debakey VA Medical Center in Houston. Dr. Mathew has served as a consultant for and has had research funded by Janssen Pharmaceuticals.
I’m not surprised by the FDA decision, given the strong endorsement from the advisory committees in mid-February based on the drug’s benefit-to-risk evaluation. This is an important advance for our field, and the FDA approval will allow more patients who suffer from treatment-resistant depression to gain access to this medication.
To date, ketamine (not the intranasal esketamine spray) has been offered primarily on a fee-for-service basis or in the context of a clinical trial. I anticipate this treatment to receive broad insurance coverage, but this remains to be determined.
Dr. Sanjay J. Mathew is the Marjorie Bintliff Johnson and Raleigh White Johnson Jr. Vice Chair for Research and professor in the Menninger department of psychiatry & behavioral sciences at the Baylor College of Medicine. He also is affiliated with the Michael E. Debakey VA Medical Center in Houston. Dr. Mathew has served as a consultant for and has had research funded by Janssen Pharmaceuticals.
The spray (Spravato; Janssen Pharmaceuticals) will come in tamper-resistant prepackaged units of one, two, or three devices to deliver the prescribed doses of 28 mg, 56 mg, or 84 mg, respectively. To reduce the risk of diversion, misuse, or abuse, the drug will managed under an FDA Risk Evaluation and Management Strategy (REMS). It will only be available to prescribing clinicians who have undergone training on the risks of esketamine and the importance of monitoring patients after their dose is administered. Facilities licensed to dispense esketamine must have the ability to medically monitor patients for at least 2 hours after administration. Patients will self-administer the spray and will not be able to take any of it home.
The REMS will require both prescriber and the patient to both sign a Patient Enrollment Form clearly stating that patients understand the necessity of assisted transport to leave the health care facility and that there should be no driving or use of heavy machinery for the rest of the day on which they are treated.
A boxed warning on the label will note that patients are at risk for sedation and difficulty with attention, judgment, and thinking (dissociation); abuse and misuse; and suicidal thoughts and behaviors after administration of the drug.
Despite the FDA’s caveats, the approval of intranasal esketamine is seen as a substantial win for the psychiatric community, Tiffany Farchione, MD, acting director of the FDA division of psychiatry products, said in a statement. “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition.”
“Spravato has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies,” said Mathai Mammen, MD, PhD, global head of Janssen Research and Development.
The company “is working quickly to educate and certify treatment centers in accordance with the REMS so that health care providers can offer Spravato to appropriate patients,” according to a statement from Janssen. “Later this month, patients can visit www.SPRAVATO.com for a locater tool and to sign up to receive alerts when new treatment centers are available.”
Intranasal esketamine was evaluated in three short-term clinical trials and one longer-term maintenance-of-effect trial. One of the studies demonstrated a clinically significant effect in depression severity, in as little as 2 days for some patients. The two other short-term trials did not show significant benefit. However, in the maintenance study, patients in stable remission or with stable response who continued treatment with esketamine plus an oral antidepressant experienced a significantly longer time to relapse of depressive symptoms than patients on placebo spray plus an oral antidepressant. The most common side effects were disassociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders might be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine might impair attention, judgment, thinking, reaction speed, and motor skills. It may cause fetal harm; women of childbearing age should be on reliable contraception. Breastfeeding women should not use it.
.
The spray (Spravato; Janssen Pharmaceuticals) will come in tamper-resistant prepackaged units of one, two, or three devices to deliver the prescribed doses of 28 mg, 56 mg, or 84 mg, respectively. To reduce the risk of diversion, misuse, or abuse, the drug will managed under an FDA Risk Evaluation and Management Strategy (REMS). It will only be available to prescribing clinicians who have undergone training on the risks of esketamine and the importance of monitoring patients after their dose is administered. Facilities licensed to dispense esketamine must have the ability to medically monitor patients for at least 2 hours after administration. Patients will self-administer the spray and will not be able to take any of it home.
The REMS will require both prescriber and the patient to both sign a Patient Enrollment Form clearly stating that patients understand the necessity of assisted transport to leave the health care facility and that there should be no driving or use of heavy machinery for the rest of the day on which they are treated.
A boxed warning on the label will note that patients are at risk for sedation and difficulty with attention, judgment, and thinking (dissociation); abuse and misuse; and suicidal thoughts and behaviors after administration of the drug.
Despite the FDA’s caveats, the approval of intranasal esketamine is seen as a substantial win for the psychiatric community, Tiffany Farchione, MD, acting director of the FDA division of psychiatry products, said in a statement. “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition.”
“Spravato has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies,” said Mathai Mammen, MD, PhD, global head of Janssen Research and Development.
The company “is working quickly to educate and certify treatment centers in accordance with the REMS so that health care providers can offer Spravato to appropriate patients,” according to a statement from Janssen. “Later this month, patients can visit www.SPRAVATO.com for a locater tool and to sign up to receive alerts when new treatment centers are available.”
Intranasal esketamine was evaluated in three short-term clinical trials and one longer-term maintenance-of-effect trial. One of the studies demonstrated a clinically significant effect in depression severity, in as little as 2 days for some patients. The two other short-term trials did not show significant benefit. However, in the maintenance study, patients in stable remission or with stable response who continued treatment with esketamine plus an oral antidepressant experienced a significantly longer time to relapse of depressive symptoms than patients on placebo spray plus an oral antidepressant. The most common side effects were disassociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders might be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine might impair attention, judgment, thinking, reaction speed, and motor skills. It may cause fetal harm; women of childbearing age should be on reliable contraception. Breastfeeding women should not use it.
.
Scott Gottlieb to step down as FDA commissioner
According to reports, he is stepping down to spend more time with his family, who live in Westport, Conn. He splits time between there and Washington. He was confirmed by the Senate in May 2017 with five Democrats and one independent joining Republicans in voting him in.
President Trump confirmed Dr. Gottlieb’s resignation, praising him in a tweet for the “terrific job” he has done in this role and commending his efforts to help “us to lower drug prices, get a record number of generic drugs approved and onto the market, and so many other things. ”
Dr. Gottlieb’s legacy may be his work on regulating e-cigarettes, although that work is unfinished. His passion for this subject can be found in a statement made in Nov. 2018, announcing an advanced notice of proposed rule making to regulate e-cigarettes.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” Dr. Gottlieb said in the statement.
More recently, the agency announced March 4 enforcement actions aimed at both retailers and manufacturers, including requesting a meeting with Walgreens to discuss the nearly 1,800 violations the chain has amassed across the country for selling tobacco products to minors.
“Because tobacco use is almost always initiated and established during adolescence, early intervention ‒ including making sure tobacco products aren’t being marketed to, sold to, or used by kids ‒ is critical,” he said in announcing the enforcement actions. He added that the FDA will “continue vigorous enforcement activities, with a sustained campaign to monitor, penalize, and help prevent e-cigarette sales to minors in retail locations, including manufacturers’ Internet storefronts, as well as take additional steps to tackle other concerns related to the youth access and appeal of these products. The FDA is also exploring additional enforcement avenues to target violative sales and marketing practices by manufacturers and retailers.”
The American Heart Association praised Dr. Gottlieb’s work.
“Commissioner Gottlieb departs the FDA having established himself as a tireless champion of tobacco control,” the organization said in a statement. “He elevated the war on tobacco use – and particularly the epidemic of electronic cigarette use among youth – to unprecedented levels. Because of his efforts, millions more people nationwide are aware of the grave threats posed by e-cigarettes and other tobacco products that are addicting a new generation of youth. We urge the FDA in the strongest possible terms to move forward with effective regulation of an industry that continues to prioritize profits over the lives of consumers.”
Department of Health & Human Services Secretary Alex Azar acknowledged Dr. Gottlieb’s work in combating youth e-cigarette use among a number of areas that the outgoing official has had a positive impact on.
“Scott’s leadership inspired historic results from the FDA team, which delivered record approvals of both innovative treatments and affordable generic drugs, while advancing important policies to confront opioid addiction, tobacco and youth e-cigarette use, chronic disease, and more,” Secretary Azar said in a statement. “The public health of our country is better off for the work Scott and the entire FDA team have done over the last two years.”
Under his leadership, FDA has approved a record number of generic drugs, although many still are not on the market yet.
In the area of opioids, his tenure could be a mixed bag as the FDA on the one hand removed an opioid product from the market, but on the other, controversially approved a new, powerful one.
According to reports, he is stepping down to spend more time with his family, who live in Westport, Conn. He splits time between there and Washington. He was confirmed by the Senate in May 2017 with five Democrats and one independent joining Republicans in voting him in.
President Trump confirmed Dr. Gottlieb’s resignation, praising him in a tweet for the “terrific job” he has done in this role and commending his efforts to help “us to lower drug prices, get a record number of generic drugs approved and onto the market, and so many other things. ”
Dr. Gottlieb’s legacy may be his work on regulating e-cigarettes, although that work is unfinished. His passion for this subject can be found in a statement made in Nov. 2018, announcing an advanced notice of proposed rule making to regulate e-cigarettes.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” Dr. Gottlieb said in the statement.
More recently, the agency announced March 4 enforcement actions aimed at both retailers and manufacturers, including requesting a meeting with Walgreens to discuss the nearly 1,800 violations the chain has amassed across the country for selling tobacco products to minors.
“Because tobacco use is almost always initiated and established during adolescence, early intervention ‒ including making sure tobacco products aren’t being marketed to, sold to, or used by kids ‒ is critical,” he said in announcing the enforcement actions. He added that the FDA will “continue vigorous enforcement activities, with a sustained campaign to monitor, penalize, and help prevent e-cigarette sales to minors in retail locations, including manufacturers’ Internet storefronts, as well as take additional steps to tackle other concerns related to the youth access and appeal of these products. The FDA is also exploring additional enforcement avenues to target violative sales and marketing practices by manufacturers and retailers.”
The American Heart Association praised Dr. Gottlieb’s work.
“Commissioner Gottlieb departs the FDA having established himself as a tireless champion of tobacco control,” the organization said in a statement. “He elevated the war on tobacco use – and particularly the epidemic of electronic cigarette use among youth – to unprecedented levels. Because of his efforts, millions more people nationwide are aware of the grave threats posed by e-cigarettes and other tobacco products that are addicting a new generation of youth. We urge the FDA in the strongest possible terms to move forward with effective regulation of an industry that continues to prioritize profits over the lives of consumers.”
Department of Health & Human Services Secretary Alex Azar acknowledged Dr. Gottlieb’s work in combating youth e-cigarette use among a number of areas that the outgoing official has had a positive impact on.
“Scott’s leadership inspired historic results from the FDA team, which delivered record approvals of both innovative treatments and affordable generic drugs, while advancing important policies to confront opioid addiction, tobacco and youth e-cigarette use, chronic disease, and more,” Secretary Azar said in a statement. “The public health of our country is better off for the work Scott and the entire FDA team have done over the last two years.”
Under his leadership, FDA has approved a record number of generic drugs, although many still are not on the market yet.
In the area of opioids, his tenure could be a mixed bag as the FDA on the one hand removed an opioid product from the market, but on the other, controversially approved a new, powerful one.
According to reports, he is stepping down to spend more time with his family, who live in Westport, Conn. He splits time between there and Washington. He was confirmed by the Senate in May 2017 with five Democrats and one independent joining Republicans in voting him in.
President Trump confirmed Dr. Gottlieb’s resignation, praising him in a tweet for the “terrific job” he has done in this role and commending his efforts to help “us to lower drug prices, get a record number of generic drugs approved and onto the market, and so many other things. ”
Dr. Gottlieb’s legacy may be his work on regulating e-cigarettes, although that work is unfinished. His passion for this subject can be found in a statement made in Nov. 2018, announcing an advanced notice of proposed rule making to regulate e-cigarettes.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” Dr. Gottlieb said in the statement.
More recently, the agency announced March 4 enforcement actions aimed at both retailers and manufacturers, including requesting a meeting with Walgreens to discuss the nearly 1,800 violations the chain has amassed across the country for selling tobacco products to minors.
“Because tobacco use is almost always initiated and established during adolescence, early intervention ‒ including making sure tobacco products aren’t being marketed to, sold to, or used by kids ‒ is critical,” he said in announcing the enforcement actions. He added that the FDA will “continue vigorous enforcement activities, with a sustained campaign to monitor, penalize, and help prevent e-cigarette sales to minors in retail locations, including manufacturers’ Internet storefronts, as well as take additional steps to tackle other concerns related to the youth access and appeal of these products. The FDA is also exploring additional enforcement avenues to target violative sales and marketing practices by manufacturers and retailers.”
The American Heart Association praised Dr. Gottlieb’s work.
“Commissioner Gottlieb departs the FDA having established himself as a tireless champion of tobacco control,” the organization said in a statement. “He elevated the war on tobacco use – and particularly the epidemic of electronic cigarette use among youth – to unprecedented levels. Because of his efforts, millions more people nationwide are aware of the grave threats posed by e-cigarettes and other tobacco products that are addicting a new generation of youth. We urge the FDA in the strongest possible terms to move forward with effective regulation of an industry that continues to prioritize profits over the lives of consumers.”
Department of Health & Human Services Secretary Alex Azar acknowledged Dr. Gottlieb’s work in combating youth e-cigarette use among a number of areas that the outgoing official has had a positive impact on.
“Scott’s leadership inspired historic results from the FDA team, which delivered record approvals of both innovative treatments and affordable generic drugs, while advancing important policies to confront opioid addiction, tobacco and youth e-cigarette use, chronic disease, and more,” Secretary Azar said in a statement. “The public health of our country is better off for the work Scott and the entire FDA team have done over the last two years.”
Under his leadership, FDA has approved a record number of generic drugs, although many still are not on the market yet.
In the area of opioids, his tenure could be a mixed bag as the FDA on the one hand removed an opioid product from the market, but on the other, controversially approved a new, powerful one.
Behavioral intervention improves physical activity in patients with diabetes
A behavioral intervention that involves regular counseling sessions could help patients with type 2 diabetes increase their levels of physical activity and decrease their amount of sedentary time, according to findings from a prospective, randomized trial of 300 physically inactive patients with type 2 diabetes.
“The primary strength of this study is the application of an intervention targeting both physical activity and sedentary time across all settings (e.g., leisure, transportation, household, and occupation), based on theoretical grounds and using several behavior-change techniques,” wrote Stefano Balducci, MD, of Sapienza University in Rome and his colleagues. The findings were published in JAMA.
Half the participants were randomized to an intervention that involved one individual theoretical counseling session with a diabetologist and eight biweekly theoretical and practical counseling sessions with an exercise specialist each year for 3 years. The other half received standard care in the form of recommendations from their general physician about increasing physical activity and decreasing sedentary time. Both groups also received the same general treatment regimen according to guidelines.
The findings showed significant increases in volume of physical activity, light-intensity physical activity, and moderate to vigorous physical activity in the intervention group during the first 4 months of the trial. Those increases also were greater than the increases seen in the usual care group. Patients in the intervention group also showed greater decreases in sedentary time, compared with those in the control group during the same time.
After 4 months, the increases in physical activity in the intervention group plateaued but remained stable until 2 years. After that, the levels of activity declined but still remained significantly higher than at baseline. The level of sedentary time also increased after 2 years but was still lower than at baseline.
By the end of the study, the intervention group accumulated 13.8 metabolic equivalent hours/week of physical activity volume, compared with 10.5 hours in the control group; 18.9 minutes/day of moderate to vigorous intensity physical activity, compared with 12.5 minutes in the control group; and 4.6 hours/day of light-intensity physical activity, compared with 3.8 hours in the control group. In regard to sedentary time, the intervention group accumulated 10.9 hours/day, compared with 11.7 hours in the control group. All differences were statistically significant.
“The present findings support the need for interventions targeting all domains of behavior to obtain substantial lifestyle changes, not limited to moderate- to vigorous-intensity physical activity, which has little effect on sedentary time,” Dr. Balducci and his coauthors wrote. “This concept is consistent with a 2018 report showing that physical activity, sedentary time, and cardiorespiratory fitness are all important for cardiometabolic health.”
For the secondary outcomes of cardiorespiratory fitness and lower-body strength, the authors saw significant improvements in the intervention group, whereas the control group showed a worsening in those outcomes. The intervention group also showed significant improvements in fasting plasma glucose level, systolic blood pressure, total coronary heart disease 10-year risk score, and fatal coronary heart disease 10-year risk score. They also had significantly greater improvements than did the control group in total stroke risk score, hemoglobin A1c, fasting plasma glucose levels, and coronary heart disease risk.
In all, there were 41 adverse events in the intervention group, compared with 59 in the control group, outside of the sessions. During the sessions, participants in the intervention group experienced mild hypoglycemia (8 episodes), tachycardia/arrhythmia (3), and musculoskeletal injury or discomfort (19).
One of the limitations highlighted by the authors was that the benefits of their strategy could vary in other cohorts because of differences in climatic, socioeconomic, or cultural settings.
The study was supported by the Metabolic Fitness Association. Three authors declared grants and personal fees from pharmaceutical companies, and one author was an employee of Technogym. No other conflicts of interest were declared.
SOURCE: Balducci S et al. JAMA. 2019;321:880-90.
A behavioral intervention that involves regular counseling sessions could help patients with type 2 diabetes increase their levels of physical activity and decrease their amount of sedentary time, according to findings from a prospective, randomized trial of 300 physically inactive patients with type 2 diabetes.
“The primary strength of this study is the application of an intervention targeting both physical activity and sedentary time across all settings (e.g., leisure, transportation, household, and occupation), based on theoretical grounds and using several behavior-change techniques,” wrote Stefano Balducci, MD, of Sapienza University in Rome and his colleagues. The findings were published in JAMA.
Half the participants were randomized to an intervention that involved one individual theoretical counseling session with a diabetologist and eight biweekly theoretical and practical counseling sessions with an exercise specialist each year for 3 years. The other half received standard care in the form of recommendations from their general physician about increasing physical activity and decreasing sedentary time. Both groups also received the same general treatment regimen according to guidelines.
The findings showed significant increases in volume of physical activity, light-intensity physical activity, and moderate to vigorous physical activity in the intervention group during the first 4 months of the trial. Those increases also were greater than the increases seen in the usual care group. Patients in the intervention group also showed greater decreases in sedentary time, compared with those in the control group during the same time.
After 4 months, the increases in physical activity in the intervention group plateaued but remained stable until 2 years. After that, the levels of activity declined but still remained significantly higher than at baseline. The level of sedentary time also increased after 2 years but was still lower than at baseline.
By the end of the study, the intervention group accumulated 13.8 metabolic equivalent hours/week of physical activity volume, compared with 10.5 hours in the control group; 18.9 minutes/day of moderate to vigorous intensity physical activity, compared with 12.5 minutes in the control group; and 4.6 hours/day of light-intensity physical activity, compared with 3.8 hours in the control group. In regard to sedentary time, the intervention group accumulated 10.9 hours/day, compared with 11.7 hours in the control group. All differences were statistically significant.
“The present findings support the need for interventions targeting all domains of behavior to obtain substantial lifestyle changes, not limited to moderate- to vigorous-intensity physical activity, which has little effect on sedentary time,” Dr. Balducci and his coauthors wrote. “This concept is consistent with a 2018 report showing that physical activity, sedentary time, and cardiorespiratory fitness are all important for cardiometabolic health.”
For the secondary outcomes of cardiorespiratory fitness and lower-body strength, the authors saw significant improvements in the intervention group, whereas the control group showed a worsening in those outcomes. The intervention group also showed significant improvements in fasting plasma glucose level, systolic blood pressure, total coronary heart disease 10-year risk score, and fatal coronary heart disease 10-year risk score. They also had significantly greater improvements than did the control group in total stroke risk score, hemoglobin A1c, fasting plasma glucose levels, and coronary heart disease risk.
In all, there were 41 adverse events in the intervention group, compared with 59 in the control group, outside of the sessions. During the sessions, participants in the intervention group experienced mild hypoglycemia (8 episodes), tachycardia/arrhythmia (3), and musculoskeletal injury or discomfort (19).
One of the limitations highlighted by the authors was that the benefits of their strategy could vary in other cohorts because of differences in climatic, socioeconomic, or cultural settings.
The study was supported by the Metabolic Fitness Association. Three authors declared grants and personal fees from pharmaceutical companies, and one author was an employee of Technogym. No other conflicts of interest were declared.
SOURCE: Balducci S et al. JAMA. 2019;321:880-90.
A behavioral intervention that involves regular counseling sessions could help patients with type 2 diabetes increase their levels of physical activity and decrease their amount of sedentary time, according to findings from a prospective, randomized trial of 300 physically inactive patients with type 2 diabetes.
“The primary strength of this study is the application of an intervention targeting both physical activity and sedentary time across all settings (e.g., leisure, transportation, household, and occupation), based on theoretical grounds and using several behavior-change techniques,” wrote Stefano Balducci, MD, of Sapienza University in Rome and his colleagues. The findings were published in JAMA.
Half the participants were randomized to an intervention that involved one individual theoretical counseling session with a diabetologist and eight biweekly theoretical and practical counseling sessions with an exercise specialist each year for 3 years. The other half received standard care in the form of recommendations from their general physician about increasing physical activity and decreasing sedentary time. Both groups also received the same general treatment regimen according to guidelines.
The findings showed significant increases in volume of physical activity, light-intensity physical activity, and moderate to vigorous physical activity in the intervention group during the first 4 months of the trial. Those increases also were greater than the increases seen in the usual care group. Patients in the intervention group also showed greater decreases in sedentary time, compared with those in the control group during the same time.
After 4 months, the increases in physical activity in the intervention group plateaued but remained stable until 2 years. After that, the levels of activity declined but still remained significantly higher than at baseline. The level of sedentary time also increased after 2 years but was still lower than at baseline.
By the end of the study, the intervention group accumulated 13.8 metabolic equivalent hours/week of physical activity volume, compared with 10.5 hours in the control group; 18.9 minutes/day of moderate to vigorous intensity physical activity, compared with 12.5 minutes in the control group; and 4.6 hours/day of light-intensity physical activity, compared with 3.8 hours in the control group. In regard to sedentary time, the intervention group accumulated 10.9 hours/day, compared with 11.7 hours in the control group. All differences were statistically significant.
“The present findings support the need for interventions targeting all domains of behavior to obtain substantial lifestyle changes, not limited to moderate- to vigorous-intensity physical activity, which has little effect on sedentary time,” Dr. Balducci and his coauthors wrote. “This concept is consistent with a 2018 report showing that physical activity, sedentary time, and cardiorespiratory fitness are all important for cardiometabolic health.”
For the secondary outcomes of cardiorespiratory fitness and lower-body strength, the authors saw significant improvements in the intervention group, whereas the control group showed a worsening in those outcomes. The intervention group also showed significant improvements in fasting plasma glucose level, systolic blood pressure, total coronary heart disease 10-year risk score, and fatal coronary heart disease 10-year risk score. They also had significantly greater improvements than did the control group in total stroke risk score, hemoglobin A1c, fasting plasma glucose levels, and coronary heart disease risk.
In all, there were 41 adverse events in the intervention group, compared with 59 in the control group, outside of the sessions. During the sessions, participants in the intervention group experienced mild hypoglycemia (8 episodes), tachycardia/arrhythmia (3), and musculoskeletal injury or discomfort (19).
One of the limitations highlighted by the authors was that the benefits of their strategy could vary in other cohorts because of differences in climatic, socioeconomic, or cultural settings.
The study was supported by the Metabolic Fitness Association. Three authors declared grants and personal fees from pharmaceutical companies, and one author was an employee of Technogym. No other conflicts of interest were declared.
SOURCE: Balducci S et al. JAMA. 2019;321:880-90.
FROM JAMA
Teledermatology can increase efficiency
WASHINGTON – , according to a retrospective study presented at the annual meeting of the American Academy of Dermatology
Investigators previously have found that teledermatology systems, used by dermatologists to triage and manage patients, do improve patient access. Analyses of the clinical efficiency of these systems have demonstrated mixed results, however, and few such studies have been conducted in large, closed health care settings such as VA and county hospitals.
To investigate these open questions, Adam Zakaria, a third-year medical student at the University of California, San Francisco, and colleagues created a direct efficiency measure to analyze the teledermatology system at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG), which was established in January 2015. ZSFG is a public safety net hospital that serves approximately 150,000 patients annually, according to Mr. Zakaria.
Before the teledermatology system was implemented, each patient seeking to consult a ZSFG dermatologist needed a referral from a primary care provider. Appointments were given on a first-come, first-served basis, “with little consideration for the acuity or the severity of the patient’s complaint,” Mr. Zakaria said at the meeting. Since the teledermatology system has been put in place, referring providers have submitted brief clinical histories and relevant photographs to the system. Once per week, a UCSF dermatology provider and three to four UCSF dermatology residents meet to review cases and decide whether patients can be treated by their primary care providers with recommendations from teledermatology, or whether they need to be seen in person at the dermatology clinic for further evaluation.
The investigators compared data for two patient cohorts: Patients scheduled for in-person clinic visits between June 2014 and December 2014 (the preteledermatology sample), and the second cohort, patients who were triaged through the teledermatology system between June 2017 and December 2017 and who only received a clinic appointment if they could not be managed by their referring provider with teledermatology recommendations (the postteledermatology sample). Data came from chart review, administrative record review, and records from the specialty care and diagnostics department at ZSFG.
Patient wait times for the live clinic and total patient cases handled per month were chosen as measures of accessibility. The measures of efficiency were the number of cases handled per dermatologist hour and the percentage of referrals managed without a live visit. Mr. Zakaria and colleagues performed two-tailed t-tests for each measure.
The analysis included 11,586 patients. Approximately 50% of the sample identified as nonwhite, approximately one-third of patients had a native language other than English, and more than three-quarters of patients had a form of public health insurance.
After the hospital implemented teledermatology, patient wait times decreased significantly (84.6 days vs. 6.7 days; P less than .001), total cases handled per month increased significantly (754 vs. 902; P = .008). In the postteledermatology period, 61.8% of teledermatology consults were handled without a live visit.
After the implementation of teledermatology, the number of cases handled per dermatologist hour increased from 2.27 to 2.63, which was statistically significant (P = .01). The total time that dermatologists spent reviewing teledermatology cases or seeing patients in the live dermatology clinic increased from 332 hours per month to 342 hours per month, an increase that was not statistically significant, however. When the researchers compared provider hours and resident hours, they again found no statistically significant difference.
The results indicate that “the benefits of teledermatology did carry over when applied in a large, closed health care setting,” said Mr. Zakaria. “Two future areas of investigation include evaluating the impact of teledermatology on the quality of resident education and assessing the costs and benefits that teledermatology imposes upon referring primary care providers.” Mr. Zakaria and his colleagues also are analyzing the costs of teledermatology.
SOURCE: Zakaria A et al. AAD 19, Abstract 10087.
WASHINGTON – , according to a retrospective study presented at the annual meeting of the American Academy of Dermatology
Investigators previously have found that teledermatology systems, used by dermatologists to triage and manage patients, do improve patient access. Analyses of the clinical efficiency of these systems have demonstrated mixed results, however, and few such studies have been conducted in large, closed health care settings such as VA and county hospitals.
To investigate these open questions, Adam Zakaria, a third-year medical student at the University of California, San Francisco, and colleagues created a direct efficiency measure to analyze the teledermatology system at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG), which was established in January 2015. ZSFG is a public safety net hospital that serves approximately 150,000 patients annually, according to Mr. Zakaria.
Before the teledermatology system was implemented, each patient seeking to consult a ZSFG dermatologist needed a referral from a primary care provider. Appointments were given on a first-come, first-served basis, “with little consideration for the acuity or the severity of the patient’s complaint,” Mr. Zakaria said at the meeting. Since the teledermatology system has been put in place, referring providers have submitted brief clinical histories and relevant photographs to the system. Once per week, a UCSF dermatology provider and three to four UCSF dermatology residents meet to review cases and decide whether patients can be treated by their primary care providers with recommendations from teledermatology, or whether they need to be seen in person at the dermatology clinic for further evaluation.
The investigators compared data for two patient cohorts: Patients scheduled for in-person clinic visits between June 2014 and December 2014 (the preteledermatology sample), and the second cohort, patients who were triaged through the teledermatology system between June 2017 and December 2017 and who only received a clinic appointment if they could not be managed by their referring provider with teledermatology recommendations (the postteledermatology sample). Data came from chart review, administrative record review, and records from the specialty care and diagnostics department at ZSFG.
Patient wait times for the live clinic and total patient cases handled per month were chosen as measures of accessibility. The measures of efficiency were the number of cases handled per dermatologist hour and the percentage of referrals managed without a live visit. Mr. Zakaria and colleagues performed two-tailed t-tests for each measure.
The analysis included 11,586 patients. Approximately 50% of the sample identified as nonwhite, approximately one-third of patients had a native language other than English, and more than three-quarters of patients had a form of public health insurance.
After the hospital implemented teledermatology, patient wait times decreased significantly (84.6 days vs. 6.7 days; P less than .001), total cases handled per month increased significantly (754 vs. 902; P = .008). In the postteledermatology period, 61.8% of teledermatology consults were handled without a live visit.
After the implementation of teledermatology, the number of cases handled per dermatologist hour increased from 2.27 to 2.63, which was statistically significant (P = .01). The total time that dermatologists spent reviewing teledermatology cases or seeing patients in the live dermatology clinic increased from 332 hours per month to 342 hours per month, an increase that was not statistically significant, however. When the researchers compared provider hours and resident hours, they again found no statistically significant difference.
The results indicate that “the benefits of teledermatology did carry over when applied in a large, closed health care setting,” said Mr. Zakaria. “Two future areas of investigation include evaluating the impact of teledermatology on the quality of resident education and assessing the costs and benefits that teledermatology imposes upon referring primary care providers.” Mr. Zakaria and his colleagues also are analyzing the costs of teledermatology.
SOURCE: Zakaria A et al. AAD 19, Abstract 10087.
WASHINGTON – , according to a retrospective study presented at the annual meeting of the American Academy of Dermatology
Investigators previously have found that teledermatology systems, used by dermatologists to triage and manage patients, do improve patient access. Analyses of the clinical efficiency of these systems have demonstrated mixed results, however, and few such studies have been conducted in large, closed health care settings such as VA and county hospitals.
To investigate these open questions, Adam Zakaria, a third-year medical student at the University of California, San Francisco, and colleagues created a direct efficiency measure to analyze the teledermatology system at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG), which was established in January 2015. ZSFG is a public safety net hospital that serves approximately 150,000 patients annually, according to Mr. Zakaria.
Before the teledermatology system was implemented, each patient seeking to consult a ZSFG dermatologist needed a referral from a primary care provider. Appointments were given on a first-come, first-served basis, “with little consideration for the acuity or the severity of the patient’s complaint,” Mr. Zakaria said at the meeting. Since the teledermatology system has been put in place, referring providers have submitted brief clinical histories and relevant photographs to the system. Once per week, a UCSF dermatology provider and three to four UCSF dermatology residents meet to review cases and decide whether patients can be treated by their primary care providers with recommendations from teledermatology, or whether they need to be seen in person at the dermatology clinic for further evaluation.
The investigators compared data for two patient cohorts: Patients scheduled for in-person clinic visits between June 2014 and December 2014 (the preteledermatology sample), and the second cohort, patients who were triaged through the teledermatology system between June 2017 and December 2017 and who only received a clinic appointment if they could not be managed by their referring provider with teledermatology recommendations (the postteledermatology sample). Data came from chart review, administrative record review, and records from the specialty care and diagnostics department at ZSFG.
Patient wait times for the live clinic and total patient cases handled per month were chosen as measures of accessibility. The measures of efficiency were the number of cases handled per dermatologist hour and the percentage of referrals managed without a live visit. Mr. Zakaria and colleagues performed two-tailed t-tests for each measure.
The analysis included 11,586 patients. Approximately 50% of the sample identified as nonwhite, approximately one-third of patients had a native language other than English, and more than three-quarters of patients had a form of public health insurance.
After the hospital implemented teledermatology, patient wait times decreased significantly (84.6 days vs. 6.7 days; P less than .001), total cases handled per month increased significantly (754 vs. 902; P = .008). In the postteledermatology period, 61.8% of teledermatology consults were handled without a live visit.
After the implementation of teledermatology, the number of cases handled per dermatologist hour increased from 2.27 to 2.63, which was statistically significant (P = .01). The total time that dermatologists spent reviewing teledermatology cases or seeing patients in the live dermatology clinic increased from 332 hours per month to 342 hours per month, an increase that was not statistically significant, however. When the researchers compared provider hours and resident hours, they again found no statistically significant difference.
The results indicate that “the benefits of teledermatology did carry over when applied in a large, closed health care setting,” said Mr. Zakaria. “Two future areas of investigation include evaluating the impact of teledermatology on the quality of resident education and assessing the costs and benefits that teledermatology imposes upon referring primary care providers.” Mr. Zakaria and his colleagues also are analyzing the costs of teledermatology.
SOURCE: Zakaria A et al. AAD 19, Abstract 10087.
REPORTING FROM AAD 19
Report: Cutting sodium consumption recommended
according to a report outlining the first-ever Dietary Reference Intakes (DRIs) recommendation intended to address chronic disease risk.
For individuals aged 14 years and older consuming sodium above that level, cutting back could reduce their risk for hypertension and other chronic diseases, according to the report from the National Academies of Sciences, Engineering, and Medicine.
That cutoff, referred to as a Chronic Disease Risk Reduction Intake (CDRR), represents an expansion of the DRIs model beyond the Recommended Dietary Allowance (RDA) and other measures of adequacy, and the Tolerable Upper Intake Level (UL), which is the maximum intake unlikely to result in adverse health effects, a report author said in a press conference.
“CDRR is a level now that will join all the rest of the alphabet soup and be a part of how we describe recommended dietary intakes,” said Virginia A. Stallings, MD, chair of the committee that reviewed the sodium and potassium DRIs. Most U.S. adults are already consuming sodium above the recommended CDRR, said Dr. Stallings, who is a professor of pediatrics at the University of Pennsylvania, Philadelphia, and the director of the Nutrition Center at Children’s Hospital of Philadelphia.
The recommendation to reduce sodium intakes to below 2,300 mg/day applies to both hypertensive and normotensive individuals, and it could be particularly beneficial in older adults, non-Hispanic blacks, and other groups at higher risk of cardiovascular disease, Dr. Stallings and her coauthors of the new report wrote. The DRIs established in 2005 for both sodium and potassium are also updated based on new methodology in this report
Lower sodium CDRRs were set for younger individuals. Children aged 1-3 years should cut back if sodium intake is above 1,200 mg/day, while the levels for children aged 4-8 years and 9-13 years were set at 1,500 and 1,800 mg/day, respectively, according to the report.
By contrast, authors of this report were unable to establish a CDRR level for potassium based on current evidence. However, that doesn’t rule out the possibility that changing potassium intake could be beneficial, they suggested, adding that the effects of potassium need to be further explored.
Sodium and potassium play important roles in maintaining physiologic homeostasis, and they have also been implicated in risk of cardiovascular disease, mainly through their effects on blood pressure, and other chronic diseases.
“The unique nature of potassium and sodium – that is, the coexistence of their essentiality with a relationship to adverse health effects, including chronic disease risk – necessitated a new approach to the review of intake recommendations for these nutrients within the [DRI] context,” the report reads. The report also affirms, and in some cases revises, levels of sodium and potassium assumed to be adequate in healthy individuals that had been established in 2005. The sodium Adequate Intake (AI) levels for individuals aged 14-50 years is unchanged at 1,500 mg daily, but that for individuals aged 51 years and older has been increased to the 1,500-mg level.
“As we examined the evidence and looked specifically at those age cuts, there was no evidence that older people needed less sodium,” Dr. Stallings said in the press conference.
Potassium AIs were decreased for most age groups. For adults, the new recommended potassium AIs are 3,400 mg/day in men and 2,600 mg/day in women, whereas the AI for potassium was 4,700 mg/day for all adults in the 2005 recommendations.
In 2005, much of the evidence used to establish the potassium AI values was based on research studies that included potassium supplementation, rather than simply potassium intake in the usual diet. “In our process, we did not use supplementation studies, but we used the intake of apparently healthy people,” Dr. Stallings said in the press conference.
Less than half of U.S. and Canadian adults have potassium intakes that meet or exceed the potassium AI, with intakes lowest among non-Hispanic blacks, Dr. Stallings said in the press conference.
Dietary potassium intake is related to fruit and vegetable consumption, which rarely meets the recommended servings per day, Dr. Stallings and her colleagues wrote in a preface to the National Academies report. Milk, white potatoes, and fruit are higher sources of dietary potassium, she said, while coffee is the leading source of potassium for Americans aged 51 years and older.
By contrast, most sodium in the modern diet comes from commercially prepared foods and beverages, instead of consumers adding salt at the time of cooking or eating, Dr. Stallings wrote.
“For the desired public health benefit of reduced sodium intake to be achieved, more attention must be paid by industry to reducing sodium in the food supply and by consumers who have the needed sodium content information and an understanding of how to make health-inspired food choices,” they wrote in the report.
The American Heart Association’s CEO, Nancy Brown, expressed her support for the new recommendation for sodium intake. The recommendation “aligns with what the American Heart Association and other prominent public health organizations have been saying for years: We must eat less salt,” she said.
“Our excessive sodium intake isn’t entirely driven by the salt shaker; it’s largely controlled by the food industry. More than 70 percent of sodium consumed is added to food before it reaches our plates. It is added in restaurants and during the manufacturing of processed and prepackaged foods,” she claimed. “We hope this report encourages the Food and Drug Administration to quickly release its voluntary sodium reduction targets for the food industry. School leaders should also take note and reject the recent U.S. Department of Agriculture decision to weaken sodium standards in school meals and continue their commitment to serve students healthier foods.”
The DRIs report on sodium and potassium was supported by contracts between the National Academy of Sciences and the Centers for Disease Control, Food and Drug Administration, Health Canada, National Institutes of Health, Public Health Agency of Canada, and the Department of Agriculture. Partial support also came from the National Academy of Sciences W. K. Kellogg Foundation Fund and the National Academy of Medicine.
SOURCE: National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for sodium and potassium. Washington: The National Academies Press. doi: 10.17226/25353.
according to a report outlining the first-ever Dietary Reference Intakes (DRIs) recommendation intended to address chronic disease risk.
For individuals aged 14 years and older consuming sodium above that level, cutting back could reduce their risk for hypertension and other chronic diseases, according to the report from the National Academies of Sciences, Engineering, and Medicine.
That cutoff, referred to as a Chronic Disease Risk Reduction Intake (CDRR), represents an expansion of the DRIs model beyond the Recommended Dietary Allowance (RDA) and other measures of adequacy, and the Tolerable Upper Intake Level (UL), which is the maximum intake unlikely to result in adverse health effects, a report author said in a press conference.
“CDRR is a level now that will join all the rest of the alphabet soup and be a part of how we describe recommended dietary intakes,” said Virginia A. Stallings, MD, chair of the committee that reviewed the sodium and potassium DRIs. Most U.S. adults are already consuming sodium above the recommended CDRR, said Dr. Stallings, who is a professor of pediatrics at the University of Pennsylvania, Philadelphia, and the director of the Nutrition Center at Children’s Hospital of Philadelphia.
The recommendation to reduce sodium intakes to below 2,300 mg/day applies to both hypertensive and normotensive individuals, and it could be particularly beneficial in older adults, non-Hispanic blacks, and other groups at higher risk of cardiovascular disease, Dr. Stallings and her coauthors of the new report wrote. The DRIs established in 2005 for both sodium and potassium are also updated based on new methodology in this report
Lower sodium CDRRs were set for younger individuals. Children aged 1-3 years should cut back if sodium intake is above 1,200 mg/day, while the levels for children aged 4-8 years and 9-13 years were set at 1,500 and 1,800 mg/day, respectively, according to the report.
By contrast, authors of this report were unable to establish a CDRR level for potassium based on current evidence. However, that doesn’t rule out the possibility that changing potassium intake could be beneficial, they suggested, adding that the effects of potassium need to be further explored.
Sodium and potassium play important roles in maintaining physiologic homeostasis, and they have also been implicated in risk of cardiovascular disease, mainly through their effects on blood pressure, and other chronic diseases.
“The unique nature of potassium and sodium – that is, the coexistence of their essentiality with a relationship to adverse health effects, including chronic disease risk – necessitated a new approach to the review of intake recommendations for these nutrients within the [DRI] context,” the report reads. The report also affirms, and in some cases revises, levels of sodium and potassium assumed to be adequate in healthy individuals that had been established in 2005. The sodium Adequate Intake (AI) levels for individuals aged 14-50 years is unchanged at 1,500 mg daily, but that for individuals aged 51 years and older has been increased to the 1,500-mg level.
“As we examined the evidence and looked specifically at those age cuts, there was no evidence that older people needed less sodium,” Dr. Stallings said in the press conference.
Potassium AIs were decreased for most age groups. For adults, the new recommended potassium AIs are 3,400 mg/day in men and 2,600 mg/day in women, whereas the AI for potassium was 4,700 mg/day for all adults in the 2005 recommendations.
In 2005, much of the evidence used to establish the potassium AI values was based on research studies that included potassium supplementation, rather than simply potassium intake in the usual diet. “In our process, we did not use supplementation studies, but we used the intake of apparently healthy people,” Dr. Stallings said in the press conference.
Less than half of U.S. and Canadian adults have potassium intakes that meet or exceed the potassium AI, with intakes lowest among non-Hispanic blacks, Dr. Stallings said in the press conference.
Dietary potassium intake is related to fruit and vegetable consumption, which rarely meets the recommended servings per day, Dr. Stallings and her colleagues wrote in a preface to the National Academies report. Milk, white potatoes, and fruit are higher sources of dietary potassium, she said, while coffee is the leading source of potassium for Americans aged 51 years and older.
By contrast, most sodium in the modern diet comes from commercially prepared foods and beverages, instead of consumers adding salt at the time of cooking or eating, Dr. Stallings wrote.
“For the desired public health benefit of reduced sodium intake to be achieved, more attention must be paid by industry to reducing sodium in the food supply and by consumers who have the needed sodium content information and an understanding of how to make health-inspired food choices,” they wrote in the report.
The American Heart Association’s CEO, Nancy Brown, expressed her support for the new recommendation for sodium intake. The recommendation “aligns with what the American Heart Association and other prominent public health organizations have been saying for years: We must eat less salt,” she said.
“Our excessive sodium intake isn’t entirely driven by the salt shaker; it’s largely controlled by the food industry. More than 70 percent of sodium consumed is added to food before it reaches our plates. It is added in restaurants and during the manufacturing of processed and prepackaged foods,” she claimed. “We hope this report encourages the Food and Drug Administration to quickly release its voluntary sodium reduction targets for the food industry. School leaders should also take note and reject the recent U.S. Department of Agriculture decision to weaken sodium standards in school meals and continue their commitment to serve students healthier foods.”
The DRIs report on sodium and potassium was supported by contracts between the National Academy of Sciences and the Centers for Disease Control, Food and Drug Administration, Health Canada, National Institutes of Health, Public Health Agency of Canada, and the Department of Agriculture. Partial support also came from the National Academy of Sciences W. K. Kellogg Foundation Fund and the National Academy of Medicine.
SOURCE: National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for sodium and potassium. Washington: The National Academies Press. doi: 10.17226/25353.
according to a report outlining the first-ever Dietary Reference Intakes (DRIs) recommendation intended to address chronic disease risk.
For individuals aged 14 years and older consuming sodium above that level, cutting back could reduce their risk for hypertension and other chronic diseases, according to the report from the National Academies of Sciences, Engineering, and Medicine.
That cutoff, referred to as a Chronic Disease Risk Reduction Intake (CDRR), represents an expansion of the DRIs model beyond the Recommended Dietary Allowance (RDA) and other measures of adequacy, and the Tolerable Upper Intake Level (UL), which is the maximum intake unlikely to result in adverse health effects, a report author said in a press conference.
“CDRR is a level now that will join all the rest of the alphabet soup and be a part of how we describe recommended dietary intakes,” said Virginia A. Stallings, MD, chair of the committee that reviewed the sodium and potassium DRIs. Most U.S. adults are already consuming sodium above the recommended CDRR, said Dr. Stallings, who is a professor of pediatrics at the University of Pennsylvania, Philadelphia, and the director of the Nutrition Center at Children’s Hospital of Philadelphia.
The recommendation to reduce sodium intakes to below 2,300 mg/day applies to both hypertensive and normotensive individuals, and it could be particularly beneficial in older adults, non-Hispanic blacks, and other groups at higher risk of cardiovascular disease, Dr. Stallings and her coauthors of the new report wrote. The DRIs established in 2005 for both sodium and potassium are also updated based on new methodology in this report
Lower sodium CDRRs were set for younger individuals. Children aged 1-3 years should cut back if sodium intake is above 1,200 mg/day, while the levels for children aged 4-8 years and 9-13 years were set at 1,500 and 1,800 mg/day, respectively, according to the report.
By contrast, authors of this report were unable to establish a CDRR level for potassium based on current evidence. However, that doesn’t rule out the possibility that changing potassium intake could be beneficial, they suggested, adding that the effects of potassium need to be further explored.
Sodium and potassium play important roles in maintaining physiologic homeostasis, and they have also been implicated in risk of cardiovascular disease, mainly through their effects on blood pressure, and other chronic diseases.
“The unique nature of potassium and sodium – that is, the coexistence of their essentiality with a relationship to adverse health effects, including chronic disease risk – necessitated a new approach to the review of intake recommendations for these nutrients within the [DRI] context,” the report reads. The report also affirms, and in some cases revises, levels of sodium and potassium assumed to be adequate in healthy individuals that had been established in 2005. The sodium Adequate Intake (AI) levels for individuals aged 14-50 years is unchanged at 1,500 mg daily, but that for individuals aged 51 years and older has been increased to the 1,500-mg level.
“As we examined the evidence and looked specifically at those age cuts, there was no evidence that older people needed less sodium,” Dr. Stallings said in the press conference.
Potassium AIs were decreased for most age groups. For adults, the new recommended potassium AIs are 3,400 mg/day in men and 2,600 mg/day in women, whereas the AI for potassium was 4,700 mg/day for all adults in the 2005 recommendations.
In 2005, much of the evidence used to establish the potassium AI values was based on research studies that included potassium supplementation, rather than simply potassium intake in the usual diet. “In our process, we did not use supplementation studies, but we used the intake of apparently healthy people,” Dr. Stallings said in the press conference.
Less than half of U.S. and Canadian adults have potassium intakes that meet or exceed the potassium AI, with intakes lowest among non-Hispanic blacks, Dr. Stallings said in the press conference.
Dietary potassium intake is related to fruit and vegetable consumption, which rarely meets the recommended servings per day, Dr. Stallings and her colleagues wrote in a preface to the National Academies report. Milk, white potatoes, and fruit are higher sources of dietary potassium, she said, while coffee is the leading source of potassium for Americans aged 51 years and older.
By contrast, most sodium in the modern diet comes from commercially prepared foods and beverages, instead of consumers adding salt at the time of cooking or eating, Dr. Stallings wrote.
“For the desired public health benefit of reduced sodium intake to be achieved, more attention must be paid by industry to reducing sodium in the food supply and by consumers who have the needed sodium content information and an understanding of how to make health-inspired food choices,” they wrote in the report.
The American Heart Association’s CEO, Nancy Brown, expressed her support for the new recommendation for sodium intake. The recommendation “aligns with what the American Heart Association and other prominent public health organizations have been saying for years: We must eat less salt,” she said.
“Our excessive sodium intake isn’t entirely driven by the salt shaker; it’s largely controlled by the food industry. More than 70 percent of sodium consumed is added to food before it reaches our plates. It is added in restaurants and during the manufacturing of processed and prepackaged foods,” she claimed. “We hope this report encourages the Food and Drug Administration to quickly release its voluntary sodium reduction targets for the food industry. School leaders should also take note and reject the recent U.S. Department of Agriculture decision to weaken sodium standards in school meals and continue their commitment to serve students healthier foods.”
The DRIs report on sodium and potassium was supported by contracts between the National Academy of Sciences and the Centers for Disease Control, Food and Drug Administration, Health Canada, National Institutes of Health, Public Health Agency of Canada, and the Department of Agriculture. Partial support also came from the National Academy of Sciences W. K. Kellogg Foundation Fund and the National Academy of Medicine.
SOURCE: National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for sodium and potassium. Washington: The National Academies Press. doi: 10.17226/25353.
Food allergies and atopic dermatitis: What is the evidence?
WASHINGTON – The and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.
Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.
There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.
In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.
Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.
WASHINGTON – The and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.
Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.
There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.
In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.
Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.
WASHINGTON – The and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.
Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.
There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.
In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.
Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.
REPORTING FROM AAD 2019