MDedge Neurology

On March 13, most of the United States and Canada will advance the clock an hour to be on Daylight Saving Time. Most other countries in the Northern Hemisphere will do the same within a few weeks; and many countries across the Southern Hemisphere turn the clock back an hour around the same time. A friend of mine, who spent time on Capitol Hill, once told me that whether it’s adjusting to Daylight Saving Time (and losing an hour of sleep) or switching back to Standard Time (and picking up an hour), large numbers of Americans call their member of Congress every season to complain.

Why are so many of us annoyed by the semi-annual resetting of clocks? It turns out that there are biological reasons for our discomfort with time changes. Those reasons also come into play when we change time zones as we travel, when we work on the night shift, or when we live at higher latitudes, where depressive symptoms from seasonal affective disorder (SAD) can plague us as the period of daylight progressively shortens in winter.
 

Our internal clock(s)

Each of us has a biological master clock keeping track of where we are in our 24-hour day, making ongoing time-of-day-appropriate physical and neurologic adjustments. We refer to those automatic adjustments as “circadian” rhythms – from the Latin, for “around a day” rhythms.

©Thinglass/thinkstockphotos.com

One of the most important regulated functions that is influenced by this time keeping is our sleep-wake cycle. Our brain’s hypothalamus has a kind of “master clock” that receives inputs directly from our eyes, which is how our brain sets our daily cycle period at about 24 hours.

This master clock turns on a tiny structure in our brains, called the pineal gland, to release more of a sleep-inducing chemical, called melatonin, about the same time every evening. The level of melatonin slowly increases to reach maximum deep sleep in the night, then slowly declines as you advance toward morning awakening. The shift from darkness to daylight in the morning, causing your initial morning awakening, releases the excitatory neuromodulator norepinephrine, which, with other chemicals, “turns on the lights” in your brain.

That works well most of the time – but no one told your brain that you were going to arbitrarily go to bed an hour earlier (or in the fall, later) on Circadian Rhythm Time!

We also obviously shift the time on the mechanical clock – requiring a reset of the brain’s master clock – when we travel across time zones or work the night shift. That type of desynchronization of our master clock from the mechanical clock puts our waking and sleeping behaviors out of sync with the production of brain chemicals that affect our alertness and mood. The result may be that you find yourself tired, but not sleepy, and often grumpy or even depressed. As an example, on average, people who work the night shift are just a little bit more anxious and depressed than people who get up to rise and shine with the sun every morning.
 

Seasonal affective disorder

An extreme example of this desynchronization of the master clock can manifest as SAD. SAD is a type of depression that’s related to seasonal transitions. The most commonly cited cases of SAD are for the fall-to-winter transition. In North America, its prevalence is significantly influenced by the distance of one’s place of residence from the equator – with about 12 times the impact in Alaska versus Florida. Of note, a weaker effect of latitude has been recorded in Europe, where more settled populations have had thousands of years to biologically and culturally adapt to their seasonal patterns.

What can we do about our clocks being messed with?

The most common treatment for SAD is light therapy, in which patients sit or work under artificial lights in an early-morning period, to try to advance the chemical signaling that controls sleeping and waking. Alas, light therapy doesn’t work for everyone.

Another approach, with or without the lights, is to engage in activities early in the day that produce brain chemicals to contribute to bright and cheerful waking. Those “raring-to-go” brain chemicals include norepinephrine (produced when you encounter novelty and are just having fun), acetylcholine (produced when you are carefully paying attention and are in a learning and remembering mode), serotonin (produced when you are feeling positive and just a little bit euphoric), and dopamine (produced when you feel happy and all is right with the world).

In fact, you would benefit from creating the habit of starting every day with activity that wakes up your brain. I begin my day with computerized brain exercises that are attentionally demanding, filled with novelty, and richly neurologically rewarding. I then take a brisk morning walk in which I vary my path for the sake of novelty (pumping norepinephrine), pay close attention to my surroundings (pumping acetylcholine and serotonin), and delight in all of the wonderful things out there in my world (pumping dopamine). My dog Doug enjoys this process of waking up brain and body almost as much as I do! Of course, there are a thousand other stimulating things that could help you get your day off to a lively start.

If you anticipate feeling altered by a time change, you could also think about preparing for it in advance. If it’s the semi-annual 1-hour change that throws you off kilter, you might adjust your bedtime by 10 minutes a day for the week before. If you are traveling 12 time zones (and flipping night and day), you may need to make larger adjustments over the preceding couple of weeks. Generally, without that preparation, it takes about 1 day per time zone crossed to naturally adjust your circadian rhythms.

If you’re a little lazier, like me, you might also adjust to jet lag by not forgetting to take along your little bottle of melatonin tablets, to give your pineal gland a little help. Still, that pineal gland will work hard to tell you to take a nap every day – just when you’ll probably want to be wide awake.

And if, after reading this column, you find yourself still annoyed by the upcoming 1-hour time change, you might just look around at what’s happening out there in the world and decide that your troubles are very small by comparison, and that you should delight in the “extra” hour of sunshine each evening!

Dr. Merzenich is professor emeritus, department of neuroscience, at the University of California, San Francisco. He reported serving in various positions and speaking for Posit Science and Stronger Brain, and has also received funding from the National Institutes of Health. A version of this article first appeared on Medscape.com.

On March 13, most of the United States and Canada will advance the clock an hour to be on Daylight Saving Time. Most other countries in the Northern Hemisphere will do the same within a few weeks; and many countries across the Southern Hemisphere turn the clock back an hour around the same time. A friend of mine, who spent time on Capitol Hill, once told me that whether it’s adjusting to Daylight Saving Time (and losing an hour of sleep) or switching back to Standard Time (and picking up an hour), large numbers of Americans call their member of Congress every season to complain.

Why are so many of us annoyed by the semi-annual resetting of clocks? It turns out that there are biological reasons for our discomfort with time changes. Those reasons also come into play when we change time zones as we travel, when we work on the night shift, or when we live at higher latitudes, where depressive symptoms from seasonal affective disorder (SAD) can plague us as the period of daylight progressively shortens in winter.
 

Our internal clock(s)

Each of us has a biological master clock keeping track of where we are in our 24-hour day, making ongoing time-of-day-appropriate physical and neurologic adjustments. We refer to those automatic adjustments as “circadian” rhythms – from the Latin, for “around a day” rhythms.

©Thinglass/thinkstockphotos.com

One of the most important regulated functions that is influenced by this time keeping is our sleep-wake cycle. Our brain’s hypothalamus has a kind of “master clock” that receives inputs directly from our eyes, which is how our brain sets our daily cycle period at about 24 hours.

This master clock turns on a tiny structure in our brains, called the pineal gland, to release more of a sleep-inducing chemical, called melatonin, about the same time every evening. The level of melatonin slowly increases to reach maximum deep sleep in the night, then slowly declines as you advance toward morning awakening. The shift from darkness to daylight in the morning, causing your initial morning awakening, releases the excitatory neuromodulator norepinephrine, which, with other chemicals, “turns on the lights” in your brain.

That works well most of the time – but no one told your brain that you were going to arbitrarily go to bed an hour earlier (or in the fall, later) on Circadian Rhythm Time!

We also obviously shift the time on the mechanical clock – requiring a reset of the brain’s master clock – when we travel across time zones or work the night shift. That type of desynchronization of our master clock from the mechanical clock puts our waking and sleeping behaviors out of sync with the production of brain chemicals that affect our alertness and mood. The result may be that you find yourself tired, but not sleepy, and often grumpy or even depressed. As an example, on average, people who work the night shift are just a little bit more anxious and depressed than people who get up to rise and shine with the sun every morning.
 

Seasonal affective disorder

An extreme example of this desynchronization of the master clock can manifest as SAD. SAD is a type of depression that’s related to seasonal transitions. The most commonly cited cases of SAD are for the fall-to-winter transition. In North America, its prevalence is significantly influenced by the distance of one’s place of residence from the equator – with about 12 times the impact in Alaska versus Florida. Of note, a weaker effect of latitude has been recorded in Europe, where more settled populations have had thousands of years to biologically and culturally adapt to their seasonal patterns.

What can we do about our clocks being messed with?

The most common treatment for SAD is light therapy, in which patients sit or work under artificial lights in an early-morning period, to try to advance the chemical signaling that controls sleeping and waking. Alas, light therapy doesn’t work for everyone.

Another approach, with or without the lights, is to engage in activities early in the day that produce brain chemicals to contribute to bright and cheerful waking. Those “raring-to-go” brain chemicals include norepinephrine (produced when you encounter novelty and are just having fun), acetylcholine (produced when you are carefully paying attention and are in a learning and remembering mode), serotonin (produced when you are feeling positive and just a little bit euphoric), and dopamine (produced when you feel happy and all is right with the world).

In fact, you would benefit from creating the habit of starting every day with activity that wakes up your brain. I begin my day with computerized brain exercises that are attentionally demanding, filled with novelty, and richly neurologically rewarding. I then take a brisk morning walk in which I vary my path for the sake of novelty (pumping norepinephrine), pay close attention to my surroundings (pumping acetylcholine and serotonin), and delight in all of the wonderful things out there in my world (pumping dopamine). My dog Doug enjoys this process of waking up brain and body almost as much as I do! Of course, there are a thousand other stimulating things that could help you get your day off to a lively start.

If you anticipate feeling altered by a time change, you could also think about preparing for it in advance. If it’s the semi-annual 1-hour change that throws you off kilter, you might adjust your bedtime by 10 minutes a day for the week before. If you are traveling 12 time zones (and flipping night and day), you may need to make larger adjustments over the preceding couple of weeks. Generally, without that preparation, it takes about 1 day per time zone crossed to naturally adjust your circadian rhythms.

If you’re a little lazier, like me, you might also adjust to jet lag by not forgetting to take along your little bottle of melatonin tablets, to give your pineal gland a little help. Still, that pineal gland will work hard to tell you to take a nap every day – just when you’ll probably want to be wide awake.

And if, after reading this column, you find yourself still annoyed by the upcoming 1-hour time change, you might just look around at what’s happening out there in the world and decide that your troubles are very small by comparison, and that you should delight in the “extra” hour of sunshine each evening!

Dr. Merzenich is professor emeritus, department of neuroscience, at the University of California, San Francisco. He reported serving in various positions and speaking for Posit Science and Stronger Brain, and has also received funding from the National Institutes of Health. A version of this article first appeared on Medscape.com.

On March 13, most of the United States and Canada will advance the clock an hour to be on Daylight Saving Time. Most other countries in the Northern Hemisphere will do the same within a few weeks; and many countries across the Southern Hemisphere turn the clock back an hour around the same time. A friend of mine, who spent time on Capitol Hill, once told me that whether it’s adjusting to Daylight Saving Time (and losing an hour of sleep) or switching back to Standard Time (and picking up an hour), large numbers of Americans call their member of Congress every season to complain.

Why are so many of us annoyed by the semi-annual resetting of clocks? It turns out that there are biological reasons for our discomfort with time changes. Those reasons also come into play when we change time zones as we travel, when we work on the night shift, or when we live at higher latitudes, where depressive symptoms from seasonal affective disorder (SAD) can plague us as the period of daylight progressively shortens in winter.
 

Our internal clock(s)

Each of us has a biological master clock keeping track of where we are in our 24-hour day, making ongoing time-of-day-appropriate physical and neurologic adjustments. We refer to those automatic adjustments as “circadian” rhythms – from the Latin, for “around a day” rhythms.

©Thinglass/thinkstockphotos.com

One of the most important regulated functions that is influenced by this time keeping is our sleep-wake cycle. Our brain’s hypothalamus has a kind of “master clock” that receives inputs directly from our eyes, which is how our brain sets our daily cycle period at about 24 hours.

This master clock turns on a tiny structure in our brains, called the pineal gland, to release more of a sleep-inducing chemical, called melatonin, about the same time every evening. The level of melatonin slowly increases to reach maximum deep sleep in the night, then slowly declines as you advance toward morning awakening. The shift from darkness to daylight in the morning, causing your initial morning awakening, releases the excitatory neuromodulator norepinephrine, which, with other chemicals, “turns on the lights” in your brain.

That works well most of the time – but no one told your brain that you were going to arbitrarily go to bed an hour earlier (or in the fall, later) on Circadian Rhythm Time!

We also obviously shift the time on the mechanical clock – requiring a reset of the brain’s master clock – when we travel across time zones or work the night shift. That type of desynchronization of our master clock from the mechanical clock puts our waking and sleeping behaviors out of sync with the production of brain chemicals that affect our alertness and mood. The result may be that you find yourself tired, but not sleepy, and often grumpy or even depressed. As an example, on average, people who work the night shift are just a little bit more anxious and depressed than people who get up to rise and shine with the sun every morning.
 

Seasonal affective disorder

An extreme example of this desynchronization of the master clock can manifest as SAD. SAD is a type of depression that’s related to seasonal transitions. The most commonly cited cases of SAD are for the fall-to-winter transition. In North America, its prevalence is significantly influenced by the distance of one’s place of residence from the equator – with about 12 times the impact in Alaska versus Florida. Of note, a weaker effect of latitude has been recorded in Europe, where more settled populations have had thousands of years to biologically and culturally adapt to their seasonal patterns.

What can we do about our clocks being messed with?

The most common treatment for SAD is light therapy, in which patients sit or work under artificial lights in an early-morning period, to try to advance the chemical signaling that controls sleeping and waking. Alas, light therapy doesn’t work for everyone.

Another approach, with or without the lights, is to engage in activities early in the day that produce brain chemicals to contribute to bright and cheerful waking. Those “raring-to-go” brain chemicals include norepinephrine (produced when you encounter novelty and are just having fun), acetylcholine (produced when you are carefully paying attention and are in a learning and remembering mode), serotonin (produced when you are feeling positive and just a little bit euphoric), and dopamine (produced when you feel happy and all is right with the world).

In fact, you would benefit from creating the habit of starting every day with activity that wakes up your brain. I begin my day with computerized brain exercises that are attentionally demanding, filled with novelty, and richly neurologically rewarding. I then take a brisk morning walk in which I vary my path for the sake of novelty (pumping norepinephrine), pay close attention to my surroundings (pumping acetylcholine and serotonin), and delight in all of the wonderful things out there in my world (pumping dopamine). My dog Doug enjoys this process of waking up brain and body almost as much as I do! Of course, there are a thousand other stimulating things that could help you get your day off to a lively start.

If you anticipate feeling altered by a time change, you could also think about preparing for it in advance. If it’s the semi-annual 1-hour change that throws you off kilter, you might adjust your bedtime by 10 minutes a day for the week before. If you are traveling 12 time zones (and flipping night and day), you may need to make larger adjustments over the preceding couple of weeks. Generally, without that preparation, it takes about 1 day per time zone crossed to naturally adjust your circadian rhythms.

If you’re a little lazier, like me, you might also adjust to jet lag by not forgetting to take along your little bottle of melatonin tablets, to give your pineal gland a little help. Still, that pineal gland will work hard to tell you to take a nap every day – just when you’ll probably want to be wide awake.

And if, after reading this column, you find yourself still annoyed by the upcoming 1-hour time change, you might just look around at what’s happening out there in the world and decide that your troubles are very small by comparison, and that you should delight in the “extra” hour of sunshine each evening!

Dr. Merzenich is professor emeritus, department of neuroscience, at the University of California, San Francisco. He reported serving in various positions and speaking for Posit Science and Stronger Brain, and has also received funding from the National Institutes of Health. A version of this article first appeared on Medscape.com.

Magnetic Resonance Imaging has long been the standard for diagnosing and surveilling multiple sclerosis (MS), and new guidelines provide updates on the use of MRI for the diagnosis, prognosis, and treatment monitoring of MS.

MS affects approximately one million people in the United States. As family physicians, these guidelines are important to know, because we are often the ones who make the initial diagnosis of MS. Similarly, if we order the wrong imaging study, we can miss making an accurate diagnosis.

The new guidelines (MAGNIMS), which were sponsored by the Consortium of Multiple Sclerosis Centres, were published in August. The documents offers detailed guidance on the use of standardized MRI protocols as well as the use of IV gadolinium contrast agents, including in children and pregnant patients.

It is advised to use 3-D techniques (as opposed to two-dimensional) and it is noted that this is becoming more clinically available. Sagittal 3-D T2-weighted fluid-attenuated inversion recovery (FLAIR) is the core sequence considered for MS diagnosis and monitoring because of its high sensitivity. High-quality 2-D pulse sequences can be used alternatively when 3-D FLAIR is not available.

When 3 T scanners are not available, 1.5 T scanners are sufficient. However, 3 T scanners do have a higher detection rate for MS lesions. In evaluating the imaging, T2 lesion counts, gadolinium lesion counts, and interval changes should be reported.

The use of GBCAs (gadolinium-based contrast agents) is needed to diagnose MS and rule out other diseases. The time between injection of contrast should ideally be 10 minutes but no less than 5. Optic nerve MRI is recommended only in patients with atypical symptoms, such as new visual symptoms. Spinal cord MRI is also not routinely advised unless it is needed for prognosis.

When the initial MRI does not meet the full criteria of MS, brain MRI should be repeated every 6-12 months in suspected cases. The same modality should be used each time. After treatment is started, it is recommended to perform MRI without GBCAs for 3 months and annual follow ups. The use of GBCAs-free MRIs for routine follow up is a new recommendation compared to previous ones. However, if the use of GBCAs would change the management, then they should be utilized for monitoring.

The same imaging standards are recommended in pediatric patients. Spinal cord MRI should be utilized in kids with spinal cord symptoms or inconclusive brain MRI. Similar scan frequency is recommended as in adults. MRI is not contraindicated during pregnancy but should be decided on an individual basis. Standard protocols should be used as well as a magnetic field strength of 1.5 T. GBCAs should not be used during pregnancy. There are no limitations in the postpartum period.

The complete set of guidelines is quite extensive and adds to the previous guidelines published in 2017. They were first published in The Lancet Neurology.

While most of these patients will be referred to neurologists, as the primary care physician it is our responsibility to know all aspects of our patients’ diseases and treatments. While we may not be actively treating MS in these patients, we need to know their medications, how they interact with others, and how their disease is progressing

Additionally, we may be the ones asked to order MRIs for monitoring. It is imperative that we know the guidelines for how to do this.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Magnetic Resonance Imaging has long been the standard for diagnosing and surveilling multiple sclerosis (MS), and new guidelines provide updates on the use of MRI for the diagnosis, prognosis, and treatment monitoring of MS.

MS affects approximately one million people in the United States. As family physicians, these guidelines are important to know, because we are often the ones who make the initial diagnosis of MS. Similarly, if we order the wrong imaging study, we can miss making an accurate diagnosis.

The new guidelines (MAGNIMS), which were sponsored by the Consortium of Multiple Sclerosis Centres, were published in August. The documents offers detailed guidance on the use of standardized MRI protocols as well as the use of IV gadolinium contrast agents, including in children and pregnant patients.

It is advised to use 3-D techniques (as opposed to two-dimensional) and it is noted that this is becoming more clinically available. Sagittal 3-D T2-weighted fluid-attenuated inversion recovery (FLAIR) is the core sequence considered for MS diagnosis and monitoring because of its high sensitivity. High-quality 2-D pulse sequences can be used alternatively when 3-D FLAIR is not available.

When 3 T scanners are not available, 1.5 T scanners are sufficient. However, 3 T scanners do have a higher detection rate for MS lesions. In evaluating the imaging, T2 lesion counts, gadolinium lesion counts, and interval changes should be reported.

The use of GBCAs (gadolinium-based contrast agents) is needed to diagnose MS and rule out other diseases. The time between injection of contrast should ideally be 10 minutes but no less than 5. Optic nerve MRI is recommended only in patients with atypical symptoms, such as new visual symptoms. Spinal cord MRI is also not routinely advised unless it is needed for prognosis.

When the initial MRI does not meet the full criteria of MS, brain MRI should be repeated every 6-12 months in suspected cases. The same modality should be used each time. After treatment is started, it is recommended to perform MRI without GBCAs for 3 months and annual follow ups. The use of GBCAs-free MRIs for routine follow up is a new recommendation compared to previous ones. However, if the use of GBCAs would change the management, then they should be utilized for monitoring.

The same imaging standards are recommended in pediatric patients. Spinal cord MRI should be utilized in kids with spinal cord symptoms or inconclusive brain MRI. Similar scan frequency is recommended as in adults. MRI is not contraindicated during pregnancy but should be decided on an individual basis. Standard protocols should be used as well as a magnetic field strength of 1.5 T. GBCAs should not be used during pregnancy. There are no limitations in the postpartum period.

The complete set of guidelines is quite extensive and adds to the previous guidelines published in 2017. They were first published in The Lancet Neurology.

While most of these patients will be referred to neurologists, as the primary care physician it is our responsibility to know all aspects of our patients’ diseases and treatments. While we may not be actively treating MS in these patients, we need to know their medications, how they interact with others, and how their disease is progressing

Additionally, we may be the ones asked to order MRIs for monitoring. It is imperative that we know the guidelines for how to do this.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Magnetic Resonance Imaging has long been the standard for diagnosing and surveilling multiple sclerosis (MS), and new guidelines provide updates on the use of MRI for the diagnosis, prognosis, and treatment monitoring of MS.

MS affects approximately one million people in the United States. As family physicians, these guidelines are important to know, because we are often the ones who make the initial diagnosis of MS. Similarly, if we order the wrong imaging study, we can miss making an accurate diagnosis.

The new guidelines (MAGNIMS), which were sponsored by the Consortium of Multiple Sclerosis Centres, were published in August. The documents offers detailed guidance on the use of standardized MRI protocols as well as the use of IV gadolinium contrast agents, including in children and pregnant patients.

It is advised to use 3-D techniques (as opposed to two-dimensional) and it is noted that this is becoming more clinically available. Sagittal 3-D T2-weighted fluid-attenuated inversion recovery (FLAIR) is the core sequence considered for MS diagnosis and monitoring because of its high sensitivity. High-quality 2-D pulse sequences can be used alternatively when 3-D FLAIR is not available.

When 3 T scanners are not available, 1.5 T scanners are sufficient. However, 3 T scanners do have a higher detection rate for MS lesions. In evaluating the imaging, T2 lesion counts, gadolinium lesion counts, and interval changes should be reported.

The use of GBCAs (gadolinium-based contrast agents) is needed to diagnose MS and rule out other diseases. The time between injection of contrast should ideally be 10 minutes but no less than 5. Optic nerve MRI is recommended only in patients with atypical symptoms, such as new visual symptoms. Spinal cord MRI is also not routinely advised unless it is needed for prognosis.

When the initial MRI does not meet the full criteria of MS, brain MRI should be repeated every 6-12 months in suspected cases. The same modality should be used each time. After treatment is started, it is recommended to perform MRI without GBCAs for 3 months and annual follow ups. The use of GBCAs-free MRIs for routine follow up is a new recommendation compared to previous ones. However, if the use of GBCAs would change the management, then they should be utilized for monitoring.

The same imaging standards are recommended in pediatric patients. Spinal cord MRI should be utilized in kids with spinal cord symptoms or inconclusive brain MRI. Similar scan frequency is recommended as in adults. MRI is not contraindicated during pregnancy but should be decided on an individual basis. Standard protocols should be used as well as a magnetic field strength of 1.5 T. GBCAs should not be used during pregnancy. There are no limitations in the postpartum period.

The complete set of guidelines is quite extensive and adds to the previous guidelines published in 2017. They were first published in The Lancet Neurology.

While most of these patients will be referred to neurologists, as the primary care physician it is our responsibility to know all aspects of our patients’ diseases and treatments. While we may not be actively treating MS in these patients, we need to know their medications, how they interact with others, and how their disease is progressing

Additionally, we may be the ones asked to order MRIs for monitoring. It is imperative that we know the guidelines for how to do this.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

A version of this article first appeared on Medscape.com.

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

A version of this article first appeared on Medscape.com.

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

A version of this article first appeared on Medscape.com.

Mr. Jones has had multiple sclerosis (MS) since 2008. Initially it was pretty active, though I was able to bring it under control with drug A. He didn’t like the side effects, or the shots, but at that time options for MS treatment were kind of limited.

When the oral agents came out he switched to drug B. He still had some side effects on it, which he didn’t like, but his insurance didn’t cover the other oral agent that was available. So he soldiered on.

Then, in late 2019, he had an episode of optic neuritis, and a repeat MRI showed that in the last 2 years he’d had an uptick in demyelinating plaques. So, in early 2020, he switched to drug C.

Drug C has, to date, been pretty good. He’s had no side effects or relapses, and a recent brain MRI was stable.

Of course, drug C ain’t cheap. Its price isn’t even listed on ePocrates or GoodRx. So my staff and I have to do all kinds of paperwork and hoop-jumping to get it covered each year.

So in late 2021 we started the annual process, which doesn’t happen overnight. We finally received notice he’d been approved – until March 1, 2022. Only 3 months.

Given the alacrity with which these companies seem to work, we began the new authorization paperwork almost as soon as we got the last one in mid-January. This time we didn’t hear back, and every time we called they told us the application was “under review.” In the meantime, Mr. Jones’ supply of pills, which are pretty critical to his health and well-being, was gradually decreasing.

Recently, out of the blue, a 1-month supply of drug C showed up in his mailbox, along with a bill for $3,000. Mr. Jones is a career waiter at a local restaurant, and had no way to pay for this. So my staff went to work on the phones, and after a few hours got it in writing that it was being covered as a bridging supply under the manufacturer’s assistance program. Okay. That crises was averted. (I have no idea if the insurance really pays $3,000/month. Like buying a car, there can be a big difference between a drug’s asking price and what’s really paid for it).

The next morning, however, we got a note from his insurance company saying the medical reviewer had decided he didn’t need drug C, and wanted him to go back to drug B. After all, it was cheaper. I called the reviewer and argued with him. I told him he’d clinically worsened on drug B, not to mention the side effects. The reviewer said I should have mentioned that in my notes. I pointed out that it was in my notes, which had been sent along with the forms I’d filled out. He didn’t answer that, just said he’d have them fax me an appeal form.

The appeal form showed up about an hour later, so I took some time out of my weekend to fill it out. Then I faxed it back, along with (as they requested) chart notes and MRI reports dating back to 2008. Which was a lot.

So now we’ll see what happens.

Do other countries have this sort of thing? Or is this a product of the bizarre patchwork that makes up the American health care system? Different insurance companies, different subplans, and regional sub-subplans, and so on, each with a different set of rules, forms, and obstacle courses to navigate.

For all their glitzy TV commercials showing smiling, happy, multigenerational families, all looking to be in glowing health from the medical care they’re receiving, they seem to be pretty determined to keep Mr. Jones from receiving a drug that’s allowing him to continue working as a waiter 50-60 hours per week. Without it, he’d likely be unable to work and, at some point, would have to file for disability. Probably would eventually need increasingly high-cost items, going to a cane, then a walker, then a wheelchair, then a power wheelchair. ER visits, things that. In the long run, those would cost a helluva lot more than drug C.

Of course, that may be part of their game, too. Maybe they figure he’ll end up dropping off their insurance as he worsens, and then their shareholders don’t have to pay for his bad luck. I hope I’m wrong in thinking that, but such is the nature of business. And health insurance is a HUGE business.

So now I’ve faxed in the appeal forms, and can move on, for the time being, to the needs of other patients (not to mention spending time with my family). But Mr. Jones’ pill supply will run out on April 1, 2022, and I still have no idea what will happen then.

Neither does he. And for him, that’s pretty scary.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Jones has had multiple sclerosis (MS) since 2008. Initially it was pretty active, though I was able to bring it under control with drug A. He didn’t like the side effects, or the shots, but at that time options for MS treatment were kind of limited.

When the oral agents came out he switched to drug B. He still had some side effects on it, which he didn’t like, but his insurance didn’t cover the other oral agent that was available. So he soldiered on.

Then, in late 2019, he had an episode of optic neuritis, and a repeat MRI showed that in the last 2 years he’d had an uptick in demyelinating plaques. So, in early 2020, he switched to drug C.

Drug C has, to date, been pretty good. He’s had no side effects or relapses, and a recent brain MRI was stable.

Of course, drug C ain’t cheap. Its price isn’t even listed on ePocrates or GoodRx. So my staff and I have to do all kinds of paperwork and hoop-jumping to get it covered each year.

So in late 2021 we started the annual process, which doesn’t happen overnight. We finally received notice he’d been approved – until March 1, 2022. Only 3 months.

Given the alacrity with which these companies seem to work, we began the new authorization paperwork almost as soon as we got the last one in mid-January. This time we didn’t hear back, and every time we called they told us the application was “under review.” In the meantime, Mr. Jones’ supply of pills, which are pretty critical to his health and well-being, was gradually decreasing.

Recently, out of the blue, a 1-month supply of drug C showed up in his mailbox, along with a bill for $3,000. Mr. Jones is a career waiter at a local restaurant, and had no way to pay for this. So my staff went to work on the phones, and after a few hours got it in writing that it was being covered as a bridging supply under the manufacturer’s assistance program. Okay. That crises was averted. (I have no idea if the insurance really pays $3,000/month. Like buying a car, there can be a big difference between a drug’s asking price and what’s really paid for it).

The next morning, however, we got a note from his insurance company saying the medical reviewer had decided he didn’t need drug C, and wanted him to go back to drug B. After all, it was cheaper. I called the reviewer and argued with him. I told him he’d clinically worsened on drug B, not to mention the side effects. The reviewer said I should have mentioned that in my notes. I pointed out that it was in my notes, which had been sent along with the forms I’d filled out. He didn’t answer that, just said he’d have them fax me an appeal form.

The appeal form showed up about an hour later, so I took some time out of my weekend to fill it out. Then I faxed it back, along with (as they requested) chart notes and MRI reports dating back to 2008. Which was a lot.

So now we’ll see what happens.

Do other countries have this sort of thing? Or is this a product of the bizarre patchwork that makes up the American health care system? Different insurance companies, different subplans, and regional sub-subplans, and so on, each with a different set of rules, forms, and obstacle courses to navigate.

For all their glitzy TV commercials showing smiling, happy, multigenerational families, all looking to be in glowing health from the medical care they’re receiving, they seem to be pretty determined to keep Mr. Jones from receiving a drug that’s allowing him to continue working as a waiter 50-60 hours per week. Without it, he’d likely be unable to work and, at some point, would have to file for disability. Probably would eventually need increasingly high-cost items, going to a cane, then a walker, then a wheelchair, then a power wheelchair. ER visits, things that. In the long run, those would cost a helluva lot more than drug C.

Of course, that may be part of their game, too. Maybe they figure he’ll end up dropping off their insurance as he worsens, and then their shareholders don’t have to pay for his bad luck. I hope I’m wrong in thinking that, but such is the nature of business. And health insurance is a HUGE business.

So now I’ve faxed in the appeal forms, and can move on, for the time being, to the needs of other patients (not to mention spending time with my family). But Mr. Jones’ pill supply will run out on April 1, 2022, and I still have no idea what will happen then.

Neither does he. And for him, that’s pretty scary.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Jones has had multiple sclerosis (MS) since 2008. Initially it was pretty active, though I was able to bring it under control with drug A. He didn’t like the side effects, or the shots, but at that time options for MS treatment were kind of limited.

When the oral agents came out he switched to drug B. He still had some side effects on it, which he didn’t like, but his insurance didn’t cover the other oral agent that was available. So he soldiered on.

Then, in late 2019, he had an episode of optic neuritis, and a repeat MRI showed that in the last 2 years he’d had an uptick in demyelinating plaques. So, in early 2020, he switched to drug C.

Drug C has, to date, been pretty good. He’s had no side effects or relapses, and a recent brain MRI was stable.

Of course, drug C ain’t cheap. Its price isn’t even listed on ePocrates or GoodRx. So my staff and I have to do all kinds of paperwork and hoop-jumping to get it covered each year.

So in late 2021 we started the annual process, which doesn’t happen overnight. We finally received notice he’d been approved – until March 1, 2022. Only 3 months.

Given the alacrity with which these companies seem to work, we began the new authorization paperwork almost as soon as we got the last one in mid-January. This time we didn’t hear back, and every time we called they told us the application was “under review.” In the meantime, Mr. Jones’ supply of pills, which are pretty critical to his health and well-being, was gradually decreasing.

Recently, out of the blue, a 1-month supply of drug C showed up in his mailbox, along with a bill for $3,000. Mr. Jones is a career waiter at a local restaurant, and had no way to pay for this. So my staff went to work on the phones, and after a few hours got it in writing that it was being covered as a bridging supply under the manufacturer’s assistance program. Okay. That crises was averted. (I have no idea if the insurance really pays $3,000/month. Like buying a car, there can be a big difference between a drug’s asking price and what’s really paid for it).

The next morning, however, we got a note from his insurance company saying the medical reviewer had decided he didn’t need drug C, and wanted him to go back to drug B. After all, it was cheaper. I called the reviewer and argued with him. I told him he’d clinically worsened on drug B, not to mention the side effects. The reviewer said I should have mentioned that in my notes. I pointed out that it was in my notes, which had been sent along with the forms I’d filled out. He didn’t answer that, just said he’d have them fax me an appeal form.

The appeal form showed up about an hour later, so I took some time out of my weekend to fill it out. Then I faxed it back, along with (as they requested) chart notes and MRI reports dating back to 2008. Which was a lot.

So now we’ll see what happens.

Do other countries have this sort of thing? Or is this a product of the bizarre patchwork that makes up the American health care system? Different insurance companies, different subplans, and regional sub-subplans, and so on, each with a different set of rules, forms, and obstacle courses to navigate.

For all their glitzy TV commercials showing smiling, happy, multigenerational families, all looking to be in glowing health from the medical care they’re receiving, they seem to be pretty determined to keep Mr. Jones from receiving a drug that’s allowing him to continue working as a waiter 50-60 hours per week. Without it, he’d likely be unable to work and, at some point, would have to file for disability. Probably would eventually need increasingly high-cost items, going to a cane, then a walker, then a wheelchair, then a power wheelchair. ER visits, things that. In the long run, those would cost a helluva lot more than drug C.

Of course, that may be part of their game, too. Maybe they figure he’ll end up dropping off their insurance as he worsens, and then their shareholders don’t have to pay for his bad luck. I hope I’m wrong in thinking that, but such is the nature of business. And health insurance is a HUGE business.

So now I’ve faxed in the appeal forms, and can move on, for the time being, to the needs of other patients (not to mention spending time with my family). But Mr. Jones’ pill supply will run out on April 1, 2022, and I still have no idea what will happen then.

Neither does he. And for him, that’s pretty scary.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In a bid to stop abuse and diversion of the anticonvulsant gabapentin, a watchdog group is petitioning federal regulators to make the drug a controlled substance.

The nonprofit group Public Citizen has filed a petition with the U.S. Food and Drug Administration and the Drug Enforcement Administration (DEA), arguing that the medication’s risks warrant additional safeguards.

Gabapentin is a generic drug, best known under the brand name Neurontin. The petition also covers the related drug gabapentin enacarbil (Horizant).

Public Citizen requested that gabapentin come under the DEA’s Schedule V category, which already includes the similar drug pregabalin (Lyrica). Schedule V is the lowest rung on the DEA’s drug schedule, meaning it has lower potential for abuse then Schedule I through IV drugs. This tier also includes cough preparations with less than 200 milligrams of codeine.

Classifying gabapentin as a Schedule V drug would facilitate better tracking of the drug’s use and misuse and put in place educational and limitation requirements to mitigate the risk of addiction, overdose, and death, Michael Abrams, MPH, PhD, senior health researcher with Public Citizen’s Health Research Group, and colleagues write in the petition.
 

‘Widespread misuse’

There is “substantial evidence of widespread misuse” of gabapentin, plausibly helped by “extraordinary levels of off-label prescribing,” Public Citizen said in the petition.

Some estimates have pegged off-label use at more than 90%, with gabapentin prescribed for indications such as chronic cough, hiccups, postoperative pain, and postmenopausal hot flashes, the group said.

“Moreover, there are numerous reports indicating that gabapentin is widely used and diverted on the street to induce ‘highs’ or otherwise self-medicate,” Public Citizen said. “Both gabapentin and pregabalin have been empirically linked to the opioid overdose epidemic as drugs that potentiate the activity of these oftentimes deadly analgesics.”

This news organization tried several times to reach Azurity for comment but did not receive a response. Pfizer included gabapentin in the portfolio of drugs used to create the Viatris spin-off, which took place in 2020. Pfizer referred this news organization to Viatris for comment, but it also did not respond.

It is unclear how the FDA and DEA will respond to the petition. Public Citizen has received a reply from the FDA, in which the agency acknowledged receipt of the petition. However, the “acceptance of the petition for filing is a procedural matter and in no way reflects the agency’s decision on the substantive merits of the petition,” the FDA said in a letter.

As is common practice, the agency assigned a docket number for the petition, FDA-2022-P-0149. The docket’s website allows interested parties to track the issue.
 

‘Unnoticed’ abuse

There have been rising concerns about risks and abuse of gabapentin in recent years. In its petition, Public Citizen noted that the United Kingdom and several U.S. states have already sought tighter control of gabapentin prescriptions.

In 2019, the United Kingdom announced it would reclassify both pregabalin and gabapentin as class C controlled substances because of the rising numbers of deaths linked to the drugs.

As of November 2020, seven states – Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia, and West Virginia – had classified gabapentin as a schedule V drug, while another 12 states required prescription monitoring of the drug, Public Citizen noted.

In 2018, researchers at the University of Louisville, Kentucky, a state that has been hit particularly hard by the opioid crisis, tried to draw more attention to the risks of gabapentin.

“Amid the opioid epidemic, abuse of a different prescription painkiller has widely gone unnoticed,” the University said in a press release at the time.

The release highlighted a study led by Rachel Vickers Smith, PhD, assistant professor in the University of Louisville School of Nursing that was published in Psychology of Addictive Behaviors.

It included 33 individuals who reported recent recreational use of gabapentin. Use of the drug was combined with buprenorphine, other opioids, cocaine, and caffeine to produce effects such as muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling “high.”

In the press release, Dr. Vickers Smith said individuals who abuse gabapentin often mix it with opioids, marijuana, cocaine, and opioid treatment medication, compounding side effects to the central nervous system that include euphoria and sedation.

In addition, some individuals who primarily abused opioid pain medication have turned to gabapentin after law-enforcement actions made it more difficult to obtain prescription opioids, she noted.

“People are looking for other drugs to substitute for opioids, and gabapentin has filled that place for some,” Dr. Vickers Smith said. “Some have said it gives them a high similar to opioids.”
 

FDA 2019 warning

In 2019, the FDA issued a warning about serious breathing difficulties associated with gabapentin and pregabalin in patients with respiratory risk factors.

These factors include opioid use and other drugs that depress the central nervous system, as well as conditions such as chronic obstructive pulmonary disease that reduce lung function. Older patients are also at higher risk, the FDA said.

The agency noted that gabapentinoids are often co-prescribed with opioids for for medical conditions and abused in combination with opioids. Data collected in 2016 from an office-based physician survey showed 14% of patient encounters involving gabapentin also involved opioids, the FDA said.

“Our evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse,” the agency said in its 2019 alert.

A version of this article first appeared on Medscape.com.

In a bid to stop abuse and diversion of the anticonvulsant gabapentin, a watchdog group is petitioning federal regulators to make the drug a controlled substance.

The nonprofit group Public Citizen has filed a petition with the U.S. Food and Drug Administration and the Drug Enforcement Administration (DEA), arguing that the medication’s risks warrant additional safeguards.

Gabapentin is a generic drug, best known under the brand name Neurontin. The petition also covers the related drug gabapentin enacarbil (Horizant).

Public Citizen requested that gabapentin come under the DEA’s Schedule V category, which already includes the similar drug pregabalin (Lyrica). Schedule V is the lowest rung on the DEA’s drug schedule, meaning it has lower potential for abuse then Schedule I through IV drugs. This tier also includes cough preparations with less than 200 milligrams of codeine.

Classifying gabapentin as a Schedule V drug would facilitate better tracking of the drug’s use and misuse and put in place educational and limitation requirements to mitigate the risk of addiction, overdose, and death, Michael Abrams, MPH, PhD, senior health researcher with Public Citizen’s Health Research Group, and colleagues write in the petition.
 

‘Widespread misuse’

There is “substantial evidence of widespread misuse” of gabapentin, plausibly helped by “extraordinary levels of off-label prescribing,” Public Citizen said in the petition.

Some estimates have pegged off-label use at more than 90%, with gabapentin prescribed for indications such as chronic cough, hiccups, postoperative pain, and postmenopausal hot flashes, the group said.

“Moreover, there are numerous reports indicating that gabapentin is widely used and diverted on the street to induce ‘highs’ or otherwise self-medicate,” Public Citizen said. “Both gabapentin and pregabalin have been empirically linked to the opioid overdose epidemic as drugs that potentiate the activity of these oftentimes deadly analgesics.”

This news organization tried several times to reach Azurity for comment but did not receive a response. Pfizer included gabapentin in the portfolio of drugs used to create the Viatris spin-off, which took place in 2020. Pfizer referred this news organization to Viatris for comment, but it also did not respond.

It is unclear how the FDA and DEA will respond to the petition. Public Citizen has received a reply from the FDA, in which the agency acknowledged receipt of the petition. However, the “acceptance of the petition for filing is a procedural matter and in no way reflects the agency’s decision on the substantive merits of the petition,” the FDA said in a letter.

As is common practice, the agency assigned a docket number for the petition, FDA-2022-P-0149. The docket’s website allows interested parties to track the issue.
 

‘Unnoticed’ abuse

There have been rising concerns about risks and abuse of gabapentin in recent years. In its petition, Public Citizen noted that the United Kingdom and several U.S. states have already sought tighter control of gabapentin prescriptions.

In 2019, the United Kingdom announced it would reclassify both pregabalin and gabapentin as class C controlled substances because of the rising numbers of deaths linked to the drugs.

As of November 2020, seven states – Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia, and West Virginia – had classified gabapentin as a schedule V drug, while another 12 states required prescription monitoring of the drug, Public Citizen noted.

In 2018, researchers at the University of Louisville, Kentucky, a state that has been hit particularly hard by the opioid crisis, tried to draw more attention to the risks of gabapentin.

“Amid the opioid epidemic, abuse of a different prescription painkiller has widely gone unnoticed,” the University said in a press release at the time.

The release highlighted a study led by Rachel Vickers Smith, PhD, assistant professor in the University of Louisville School of Nursing that was published in Psychology of Addictive Behaviors.

It included 33 individuals who reported recent recreational use of gabapentin. Use of the drug was combined with buprenorphine, other opioids, cocaine, and caffeine to produce effects such as muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling “high.”

In the press release, Dr. Vickers Smith said individuals who abuse gabapentin often mix it with opioids, marijuana, cocaine, and opioid treatment medication, compounding side effects to the central nervous system that include euphoria and sedation.

In addition, some individuals who primarily abused opioid pain medication have turned to gabapentin after law-enforcement actions made it more difficult to obtain prescription opioids, she noted.

“People are looking for other drugs to substitute for opioids, and gabapentin has filled that place for some,” Dr. Vickers Smith said. “Some have said it gives them a high similar to opioids.”
 

FDA 2019 warning

In 2019, the FDA issued a warning about serious breathing difficulties associated with gabapentin and pregabalin in patients with respiratory risk factors.

These factors include opioid use and other drugs that depress the central nervous system, as well as conditions such as chronic obstructive pulmonary disease that reduce lung function. Older patients are also at higher risk, the FDA said.

The agency noted that gabapentinoids are often co-prescribed with opioids for for medical conditions and abused in combination with opioids. Data collected in 2016 from an office-based physician survey showed 14% of patient encounters involving gabapentin also involved opioids, the FDA said.

“Our evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse,” the agency said in its 2019 alert.

A version of this article first appeared on Medscape.com.

In a bid to stop abuse and diversion of the anticonvulsant gabapentin, a watchdog group is petitioning federal regulators to make the drug a controlled substance.

The nonprofit group Public Citizen has filed a petition with the U.S. Food and Drug Administration and the Drug Enforcement Administration (DEA), arguing that the medication’s risks warrant additional safeguards.

Gabapentin is a generic drug, best known under the brand name Neurontin. The petition also covers the related drug gabapentin enacarbil (Horizant).

Public Citizen requested that gabapentin come under the DEA’s Schedule V category, which already includes the similar drug pregabalin (Lyrica). Schedule V is the lowest rung on the DEA’s drug schedule, meaning it has lower potential for abuse then Schedule I through IV drugs. This tier also includes cough preparations with less than 200 milligrams of codeine.

Classifying gabapentin as a Schedule V drug would facilitate better tracking of the drug’s use and misuse and put in place educational and limitation requirements to mitigate the risk of addiction, overdose, and death, Michael Abrams, MPH, PhD, senior health researcher with Public Citizen’s Health Research Group, and colleagues write in the petition.
 

‘Widespread misuse’

There is “substantial evidence of widespread misuse” of gabapentin, plausibly helped by “extraordinary levels of off-label prescribing,” Public Citizen said in the petition.

Some estimates have pegged off-label use at more than 90%, with gabapentin prescribed for indications such as chronic cough, hiccups, postoperative pain, and postmenopausal hot flashes, the group said.

“Moreover, there are numerous reports indicating that gabapentin is widely used and diverted on the street to induce ‘highs’ or otherwise self-medicate,” Public Citizen said. “Both gabapentin and pregabalin have been empirically linked to the opioid overdose epidemic as drugs that potentiate the activity of these oftentimes deadly analgesics.”

This news organization tried several times to reach Azurity for comment but did not receive a response. Pfizer included gabapentin in the portfolio of drugs used to create the Viatris spin-off, which took place in 2020. Pfizer referred this news organization to Viatris for comment, but it also did not respond.

It is unclear how the FDA and DEA will respond to the petition. Public Citizen has received a reply from the FDA, in which the agency acknowledged receipt of the petition. However, the “acceptance of the petition for filing is a procedural matter and in no way reflects the agency’s decision on the substantive merits of the petition,” the FDA said in a letter.

As is common practice, the agency assigned a docket number for the petition, FDA-2022-P-0149. The docket’s website allows interested parties to track the issue.
 

‘Unnoticed’ abuse

There have been rising concerns about risks and abuse of gabapentin in recent years. In its petition, Public Citizen noted that the United Kingdom and several U.S. states have already sought tighter control of gabapentin prescriptions.

In 2019, the United Kingdom announced it would reclassify both pregabalin and gabapentin as class C controlled substances because of the rising numbers of deaths linked to the drugs.

As of November 2020, seven states – Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia, and West Virginia – had classified gabapentin as a schedule V drug, while another 12 states required prescription monitoring of the drug, Public Citizen noted.

In 2018, researchers at the University of Louisville, Kentucky, a state that has been hit particularly hard by the opioid crisis, tried to draw more attention to the risks of gabapentin.

“Amid the opioid epidemic, abuse of a different prescription painkiller has widely gone unnoticed,” the University said in a press release at the time.

The release highlighted a study led by Rachel Vickers Smith, PhD, assistant professor in the University of Louisville School of Nursing that was published in Psychology of Addictive Behaviors.

It included 33 individuals who reported recent recreational use of gabapentin. Use of the drug was combined with buprenorphine, other opioids, cocaine, and caffeine to produce effects such as muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling “high.”

In the press release, Dr. Vickers Smith said individuals who abuse gabapentin often mix it with opioids, marijuana, cocaine, and opioid treatment medication, compounding side effects to the central nervous system that include euphoria and sedation.

In addition, some individuals who primarily abused opioid pain medication have turned to gabapentin after law-enforcement actions made it more difficult to obtain prescription opioids, she noted.

“People are looking for other drugs to substitute for opioids, and gabapentin has filled that place for some,” Dr. Vickers Smith said. “Some have said it gives them a high similar to opioids.”
 

FDA 2019 warning

In 2019, the FDA issued a warning about serious breathing difficulties associated with gabapentin and pregabalin in patients with respiratory risk factors.

These factors include opioid use and other drugs that depress the central nervous system, as well as conditions such as chronic obstructive pulmonary disease that reduce lung function. Older patients are also at higher risk, the FDA said.

The agency noted that gabapentinoids are often co-prescribed with opioids for for medical conditions and abused in combination with opioids. Data collected in 2016 from an office-based physician survey showed 14% of patient encounters involving gabapentin also involved opioids, the FDA said.

“Our evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse,” the agency said in its 2019 alert.

A version of this article first appeared on Medscape.com.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.

These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.

“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.

The study was published online Jan. 20 in Frontiers in Psychiatry.
 

Anxiety a key driver?

GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.

Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.

“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.

The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).

The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).

ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.

Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.

TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
 

Links to GI disturbance, behavior

Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.

As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).

However, rates of GI disturbances in children with ASD were similar to those with DD.

Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.

Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.

Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.

They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.

The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.

The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
 

First exploration

However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”

The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.

The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.

Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.

The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”

The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.

A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.

The study received funding from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

A version of this article first appeared on Medscape.com.

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

A version of this article first appeared on Medscape.com.

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

A version of this article first appeared on Medscape.com.