Federal Practitioner

Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.

But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.

My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.

The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.

I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.

Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.

More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.

During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.

My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But, there are still many aspects of child safety, including firearms availability, that we must address, and our messages of caution should also target grandparents.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.

But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.

My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.

The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.

I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.

Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.

More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.

During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.

My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But, there are still many aspects of child safety, including firearms availability, that we must address, and our messages of caution should also target grandparents.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.

But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.

My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.

The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.

I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.

Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.

More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.

During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.

My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But, there are still many aspects of child safety, including firearms availability, that we must address, and our messages of caution should also target grandparents.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

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

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

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

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

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

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

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

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

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

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

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

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

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

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

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

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

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

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder. There are 2 broad categories of MS: relapsing, also called active MS; and progressive MS. Unfortunately, there is no cure for MS, but disease-modifying therapies (DMTs) can help prevent relapses and new central nervous system lesions in people living with active MS. For patients with the most common type of MS, relapsing-remitting MS (RRMS), DMTs are typically continued for decades while the patient has active disease. RRMS will usually transition to secondary progressive MS (SPMS), which can present as active SPMS or nonactive SPMS. The latter is the type of MS most people with RRMS eventually experience.

A 2019 study estimated that nearly 1 million people in the United States were living with MS.¹ This population estimate indicated the peak age-specific prevalence of MS was 55 to 64 years. Population data demonstrate improved mortality rates for people diagnosed with MS from 1997 to 2012 compared with prior years.² Therefore, the management of nonactive SPMS is an increasingly significant area of need. There are currently no DMTs on the market approved for nonactive SPMS, and lifelong DMTs in these patients are neither indicated nor supported by evidence. Nevertheless, the discontinuation of DMTs in nonactive SPMS has been a long-debated topic with varied opinions on how and when to discontinue.

The 2018 American Academy of Neurology (AAN) guideline recommends that clinicians advise patients with SPMS to discontinue DMT use if they do not have ongoing relapses (or gadolinium-enhanced lesions on magnetic resonance imaging activity) or have not been ambulatory (Expanded Disability Status Scale [EDSS] ≥ 7) for ≥ 2 years.³ In recent years, there has been increased research on nonactive SPMS, specifically on discontinuation of DMTs. This clinical review assesses the recent evidence from a variety of standpoints, including the effect of discontinuing DMTs on the MS disease course and quality of life (QOL) and the perspectives of patients living with MS. Based on this evidence, a conversation guide will be presented as a framework to aid with the clinician-patient discussion on discontinuing MS DMTs.

Disease Modifying Therapies

Roos and colleagues used data from 2 large MS cohorts: MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP) to compare high-efficacy vs low-efficacy DMT in both active and nonactive SPMS.⁴ In the active SPMS group, the strength of DMTs did not change disability progression, but high-efficacy DMTs reduced relapses better than the low-efficacy DMTs. On the other hand, the nonactive SPMS group saw no difference between DMTs in both relapse risk and disability progression. Another observational study of 221 patients with RRMS who discontinued DMTs noted that there were 2 independent predictors for the absence of relapse following DMT discontinuation: being aged > 45 years and the lack of relapse for ≥ 4 years prior to DMT discontinuation.⁵ Though these patients still may have been classified as RRMS, both these independent predictors for stability postdiscontinuation of DMTs are the typical characteristics of a nonactive SPMS patient.

Pathophysiology may help explain why DMT discontinuation seems to produce no adverse clinical outcomes in people with nonactive SPMS. Nonactive SPMS, which follows after RRMS, is largely correlated with age. In nonactive SPMS, there is less B and T lymphocyte migration across the blood-brain barrier. Furthermore, a lifetime of low-grade inflammation during the RRMS phase results in axonal damage and declined repair capacity, which produces the predominance of neurodegeneration in the nonactive SPMS disease process.⁶ This pathophysiologic difference between active and nonactive disease not only explains the different symptomatology of these MS subtypes, but also could explain why drugs that target the inflammatory processes more characteristic of active disease are not effective in nonactive SPMS.

Other recent studies explored the impact of age on DMT efficacy for patients with nonactive SPMS. A meta-analysis by Weidman and colleagues pooled trial data across multiple DMT classes in > 28,000 patients.⁷ The resulting regression model predicted zero efficacy of any DMT in patients who are aged > 53 years. High-efficacy DMTs only outperformed low-efficacy DMTs in people aged < 40.5 years. Another observational study by Hua and colleagues saw a similar result.⁸ This study included patients who discontinued DMT who were aged ≥ 60 years. The median follow-up time was 5.3 years. Of the 178 patients who discontinued DMTs, only 1 patient had a relapse. In this study, the age for participation provided a higher likelihood that patients included were in nonactive SPMS. Furthermore, the outcome reflects the typical presentation of nonactive SPMS where, despite the continuation or discontinuation of DMT, there was a lack of relapses. When comparing patients who discontinued DMTs with those who continued use, there was no significant difference in their 25-foot walk times, which is an objective marker for a more progressive symptom seen in nonactive MS.

The DISCOMS trial (NCT03073603) has been completed, but full results are not yet published. In this noninferiority trial, > 250 patients aged ≥ 55 years were assessed on a variety of outcomes, including relapses, EDSS score, and QOL. MS subtypes were considered at baseline, and subgroup analysis looking particularly at the SPMS population could provide further insight into its effect on MS course.

Quality of Life

Whether discontinuation of DMTs is worth considering in nonactive SPMS, it is also important to consider the risks and burdens associated with continuation. Medication administration burdens come with all MS DMTs whether there is the need to inject oneself, increased pill burden, or travel to an infusion clinic. The ever-rising costs of DMTs also can be a financial burden to the patient.⁹ All MS DMTs carry risks of adverse effects (AEs). These can range from a mild injection site reaction to severe infection, depending on the DMT used. Many of these severe AEs, such as opportunistic infections and cancer, have been associated with either an increased risk of occurrence and/or worsened outcomes in older adults who remain on DMTs, particularly moderate- to high-efficacy DMTs, such as sphingosine-1- phosphate receptor modulators, fumarates, natalizumab, alemtuzumab, cladribine, and anti-CD20 antibodies.¹⁰ In a 2019 survey of 377 patients with MS, 63.8% of respondents ranked safety as the most important reason they would consider discontinuing their DMTs.¹¹ In addition, a real-world study comparing people with nonactive SPMS who continued DMTs vs those who discontinued found that discontinuers reported better QOL.⁸

Conversation Guide for Discontinuing Therapies

The 2019 survey that assessed reasons for discontinuation also asked people with nonactive SPMS whether they thought they were in a nonactive disease stage, and what was their likelihood they would stop DMTs.¹¹ Interestingly, only 59.4% of respondents self-assessed their MS as nonactive, and just 11.9% of respondents were willing to discontinue DMTs.¹¹ These results suggest that there may be a need for patient education about nonactive SPMS and the rationale to continue or discontinue DMTs. Thus, before broaching the topic of discontinuation, explaining the nonactive SPMS subtype is important.

Even with a good understanding of nonactive SPMS, patients may be hesitant to stop using DMTs that they previously relied on to keep their MS stable. The 2019 survey ranked physician recommendation as the third highest reason to discontinue DMTs.¹¹ Taking the time to explain the clinical evidence for DMT discontinuation may help patients better understand a clinician’s recommendation and inspire more confidence.

Another important aspect of DMT discontinuation decision making is creating a plan for how the patient will be monitored to provide assurance if they experience a relapse. The 2019 survey asked patients what would be most important to them for their management plan after discontinuing DMT; magnetic resonance imaging and neurologic examination monitoring ranked the highest.¹¹ The plan should include timing for follow-up appointments and imaging, providing the patient comfort in knowing their MS will be monitored and verified for the relapse stability that is expected from nonactive SPMS. In the rare case a relapse does occur, having a contingency plan and noting the possibility of restarting DMTs is an integral part of reassuring the patient that their decision to discontinue DMTs will be treated with the utmost caution and individualized to their needs.

Lastly, highlighting which aspects of MS treatment will continue to be a priority in nonactive SPMS, such as symptomatic medication management and nonpharmacologic therapy, is important for the patient to recognize that there are still opportunities to manage this phase of MS. There are many lifestyle modifications that can be considered complementary to medical management of MS at any stage of the disease. Vascular comorbidities, such as hypertension, hyperlipidemia, and diabetes, have been associated with more rapid disability progression in MS.¹² Optimized management of these diseases may slow disability progression, in addition to the benefit of improved outcomes of the vascular comorbidity. Various formats of exercise have been studied in the MS population. A meta-analysis of aerobic, resistance, and combined exercise found benefits in these formats on health-related QOL.¹³

Many dietary strategies have been studied in MS. A recent network meta-analysis reviewed some of the more commonly studied diets, including low-fat, modified Mediterranean, ketogenic, anti-inflammatory, Paleolithic, intermittent fasting, and calorie restriction vs a usual diet.¹⁴ Although the overall quality of evidence was low, the Paleolithic and modified Mediterranean showed greater reductions in fatigue, as well as increased physical and mental QOL compared with a usual diet. The low-fat diet was associated with a reduction in fatigue. Many of these lifestyle modifications may complement optimized vascular comorbidity treatment; however, any exercise regimen or dietary change should be considered with the whole health of the patient in mind.

As with any health care decision, it is important to involve the patient in a joint decision regarding their care. This may mean giving the patient time to think about the information presented, do their own research, talk to family members or other clinicians, etc. The decision to discontinue DMT may not happen at the same appointment it is initially brought up at. It may even be reasonable to revisit the conversation later if discontinuation is not something the patient is amenable to at the time.

Conclusions

There is high-quality evidence that discontinuing DMTs in nonactive SPMS is not a major detriment to the MS disease course. Current literature also suggests that there may be benefits to discontinuation in this MS subtype in terms of QOL and meeting patient values. Additional research particularly in the nonactive SPMS population will continue to improve the knowledge and awareness of this aspect of MS DMT management. The growing evidence in this area may make discontinuation of DMT in nonactive SPMS a less-debatable topic, but it is still a major treatment decision that clinicians must thoroughly discuss with the patient to provide high-quality, patient-centered care.

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder. There are 2 broad categories of MS: relapsing, also called active MS; and progressive MS. Unfortunately, there is no cure for MS, but disease-modifying therapies (DMTs) can help prevent relapses and new central nervous system lesions in people living with active MS. For patients with the most common type of MS, relapsing-remitting MS (RRMS), DMTs are typically continued for decades while the patient has active disease. RRMS will usually transition to secondary progressive MS (SPMS), which can present as active SPMS or nonactive SPMS. The latter is the type of MS most people with RRMS eventually experience.

A 2019 study estimated that nearly 1 million people in the United States were living with MS.¹ This population estimate indicated the peak age-specific prevalence of MS was 55 to 64 years. Population data demonstrate improved mortality rates for people diagnosed with MS from 1997 to 2012 compared with prior years.² Therefore, the management of nonactive SPMS is an increasingly significant area of need. There are currently no DMTs on the market approved for nonactive SPMS, and lifelong DMTs in these patients are neither indicated nor supported by evidence. Nevertheless, the discontinuation of DMTs in nonactive SPMS has been a long-debated topic with varied opinions on how and when to discontinue.

The 2018 American Academy of Neurology (AAN) guideline recommends that clinicians advise patients with SPMS to discontinue DMT use if they do not have ongoing relapses (or gadolinium-enhanced lesions on magnetic resonance imaging activity) or have not been ambulatory (Expanded Disability Status Scale [EDSS] ≥ 7) for ≥ 2 years.³ In recent years, there has been increased research on nonactive SPMS, specifically on discontinuation of DMTs. This clinical review assesses the recent evidence from a variety of standpoints, including the effect of discontinuing DMTs on the MS disease course and quality of life (QOL) and the perspectives of patients living with MS. Based on this evidence, a conversation guide will be presented as a framework to aid with the clinician-patient discussion on discontinuing MS DMTs.

Disease Modifying Therapies

Roos and colleagues used data from 2 large MS cohorts: MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP) to compare high-efficacy vs low-efficacy DMT in both active and nonactive SPMS.⁴ In the active SPMS group, the strength of DMTs did not change disability progression, but high-efficacy DMTs reduced relapses better than the low-efficacy DMTs. On the other hand, the nonactive SPMS group saw no difference between DMTs in both relapse risk and disability progression. Another observational study of 221 patients with RRMS who discontinued DMTs noted that there were 2 independent predictors for the absence of relapse following DMT discontinuation: being aged > 45 years and the lack of relapse for ≥ 4 years prior to DMT discontinuation.⁵ Though these patients still may have been classified as RRMS, both these independent predictors for stability postdiscontinuation of DMTs are the typical characteristics of a nonactive SPMS patient.

Pathophysiology may help explain why DMT discontinuation seems to produce no adverse clinical outcomes in people with nonactive SPMS. Nonactive SPMS, which follows after RRMS, is largely correlated with age. In nonactive SPMS, there is less B and T lymphocyte migration across the blood-brain barrier. Furthermore, a lifetime of low-grade inflammation during the RRMS phase results in axonal damage and declined repair capacity, which produces the predominance of neurodegeneration in the nonactive SPMS disease process.⁶ This pathophysiologic difference between active and nonactive disease not only explains the different symptomatology of these MS subtypes, but also could explain why drugs that target the inflammatory processes more characteristic of active disease are not effective in nonactive SPMS.

Other recent studies explored the impact of age on DMT efficacy for patients with nonactive SPMS. A meta-analysis by Weidman and colleagues pooled trial data across multiple DMT classes in > 28,000 patients.⁷ The resulting regression model predicted zero efficacy of any DMT in patients who are aged > 53 years. High-efficacy DMTs only outperformed low-efficacy DMTs in people aged < 40.5 years. Another observational study by Hua and colleagues saw a similar result.⁸ This study included patients who discontinued DMT who were aged ≥ 60 years. The median follow-up time was 5.3 years. Of the 178 patients who discontinued DMTs, only 1 patient had a relapse. In this study, the age for participation provided a higher likelihood that patients included were in nonactive SPMS. Furthermore, the outcome reflects the typical presentation of nonactive SPMS where, despite the continuation or discontinuation of DMT, there was a lack of relapses. When comparing patients who discontinued DMTs with those who continued use, there was no significant difference in their 25-foot walk times, which is an objective marker for a more progressive symptom seen in nonactive MS.

The DISCOMS trial (NCT03073603) has been completed, but full results are not yet published. In this noninferiority trial, > 250 patients aged ≥ 55 years were assessed on a variety of outcomes, including relapses, EDSS score, and QOL. MS subtypes were considered at baseline, and subgroup analysis looking particularly at the SPMS population could provide further insight into its effect on MS course.

Quality of Life

Whether discontinuation of DMTs is worth considering in nonactive SPMS, it is also important to consider the risks and burdens associated with continuation. Medication administration burdens come with all MS DMTs whether there is the need to inject oneself, increased pill burden, or travel to an infusion clinic. The ever-rising costs of DMTs also can be a financial burden to the patient.⁹ All MS DMTs carry risks of adverse effects (AEs). These can range from a mild injection site reaction to severe infection, depending on the DMT used. Many of these severe AEs, such as opportunistic infections and cancer, have been associated with either an increased risk of occurrence and/or worsened outcomes in older adults who remain on DMTs, particularly moderate- to high-efficacy DMTs, such as sphingosine-1- phosphate receptor modulators, fumarates, natalizumab, alemtuzumab, cladribine, and anti-CD20 antibodies.¹⁰ In a 2019 survey of 377 patients with MS, 63.8% of respondents ranked safety as the most important reason they would consider discontinuing their DMTs.¹¹ In addition, a real-world study comparing people with nonactive SPMS who continued DMTs vs those who discontinued found that discontinuers reported better QOL.⁸

Conversation Guide for Discontinuing Therapies

The 2019 survey that assessed reasons for discontinuation also asked people with nonactive SPMS whether they thought they were in a nonactive disease stage, and what was their likelihood they would stop DMTs.¹¹ Interestingly, only 59.4% of respondents self-assessed their MS as nonactive, and just 11.9% of respondents were willing to discontinue DMTs.¹¹ These results suggest that there may be a need for patient education about nonactive SPMS and the rationale to continue or discontinue DMTs. Thus, before broaching the topic of discontinuation, explaining the nonactive SPMS subtype is important.

Even with a good understanding of nonactive SPMS, patients may be hesitant to stop using DMTs that they previously relied on to keep their MS stable. The 2019 survey ranked physician recommendation as the third highest reason to discontinue DMTs.¹¹ Taking the time to explain the clinical evidence for DMT discontinuation may help patients better understand a clinician’s recommendation and inspire more confidence.

Another important aspect of DMT discontinuation decision making is creating a plan for how the patient will be monitored to provide assurance if they experience a relapse. The 2019 survey asked patients what would be most important to them for their management plan after discontinuing DMT; magnetic resonance imaging and neurologic examination monitoring ranked the highest.¹¹ The plan should include timing for follow-up appointments and imaging, providing the patient comfort in knowing their MS will be monitored and verified for the relapse stability that is expected from nonactive SPMS. In the rare case a relapse does occur, having a contingency plan and noting the possibility of restarting DMTs is an integral part of reassuring the patient that their decision to discontinue DMTs will be treated with the utmost caution and individualized to their needs.

Lastly, highlighting which aspects of MS treatment will continue to be a priority in nonactive SPMS, such as symptomatic medication management and nonpharmacologic therapy, is important for the patient to recognize that there are still opportunities to manage this phase of MS. There are many lifestyle modifications that can be considered complementary to medical management of MS at any stage of the disease. Vascular comorbidities, such as hypertension, hyperlipidemia, and diabetes, have been associated with more rapid disability progression in MS.¹² Optimized management of these diseases may slow disability progression, in addition to the benefit of improved outcomes of the vascular comorbidity. Various formats of exercise have been studied in the MS population. A meta-analysis of aerobic, resistance, and combined exercise found benefits in these formats on health-related QOL.¹³

Many dietary strategies have been studied in MS. A recent network meta-analysis reviewed some of the more commonly studied diets, including low-fat, modified Mediterranean, ketogenic, anti-inflammatory, Paleolithic, intermittent fasting, and calorie restriction vs a usual diet.¹⁴ Although the overall quality of evidence was low, the Paleolithic and modified Mediterranean showed greater reductions in fatigue, as well as increased physical and mental QOL compared with a usual diet. The low-fat diet was associated with a reduction in fatigue. Many of these lifestyle modifications may complement optimized vascular comorbidity treatment; however, any exercise regimen or dietary change should be considered with the whole health of the patient in mind.

As with any health care decision, it is important to involve the patient in a joint decision regarding their care. This may mean giving the patient time to think about the information presented, do their own research, talk to family members or other clinicians, etc. The decision to discontinue DMT may not happen at the same appointment it is initially brought up at. It may even be reasonable to revisit the conversation later if discontinuation is not something the patient is amenable to at the time.

Conclusions

There is high-quality evidence that discontinuing DMTs in nonactive SPMS is not a major detriment to the MS disease course. Current literature also suggests that there may be benefits to discontinuation in this MS subtype in terms of QOL and meeting patient values. Additional research particularly in the nonactive SPMS population will continue to improve the knowledge and awareness of this aspect of MS DMT management. The growing evidence in this area may make discontinuation of DMT in nonactive SPMS a less-debatable topic, but it is still a major treatment decision that clinicians must thoroughly discuss with the patient to provide high-quality, patient-centered care.

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder. There are 2 broad categories of MS: relapsing, also called active MS; and progressive MS. Unfortunately, there is no cure for MS, but disease-modifying therapies (DMTs) can help prevent relapses and new central nervous system lesions in people living with active MS. For patients with the most common type of MS, relapsing-remitting MS (RRMS), DMTs are typically continued for decades while the patient has active disease. RRMS will usually transition to secondary progressive MS (SPMS), which can present as active SPMS or nonactive SPMS. The latter is the type of MS most people with RRMS eventually experience.

A 2019 study estimated that nearly 1 million people in the United States were living with MS.¹ This population estimate indicated the peak age-specific prevalence of MS was 55 to 64 years. Population data demonstrate improved mortality rates for people diagnosed with MS from 1997 to 2012 compared with prior years.² Therefore, the management of nonactive SPMS is an increasingly significant area of need. There are currently no DMTs on the market approved for nonactive SPMS, and lifelong DMTs in these patients are neither indicated nor supported by evidence. Nevertheless, the discontinuation of DMTs in nonactive SPMS has been a long-debated topic with varied opinions on how and when to discontinue.

The 2018 American Academy of Neurology (AAN) guideline recommends that clinicians advise patients with SPMS to discontinue DMT use if they do not have ongoing relapses (or gadolinium-enhanced lesions on magnetic resonance imaging activity) or have not been ambulatory (Expanded Disability Status Scale [EDSS] ≥ 7) for ≥ 2 years.³ In recent years, there has been increased research on nonactive SPMS, specifically on discontinuation of DMTs. This clinical review assesses the recent evidence from a variety of standpoints, including the effect of discontinuing DMTs on the MS disease course and quality of life (QOL) and the perspectives of patients living with MS. Based on this evidence, a conversation guide will be presented as a framework to aid with the clinician-patient discussion on discontinuing MS DMTs.

Disease Modifying Therapies

Roos and colleagues used data from 2 large MS cohorts: MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP) to compare high-efficacy vs low-efficacy DMT in both active and nonactive SPMS.⁴ In the active SPMS group, the strength of DMTs did not change disability progression, but high-efficacy DMTs reduced relapses better than the low-efficacy DMTs. On the other hand, the nonactive SPMS group saw no difference between DMTs in both relapse risk and disability progression. Another observational study of 221 patients with RRMS who discontinued DMTs noted that there were 2 independent predictors for the absence of relapse following DMT discontinuation: being aged > 45 years and the lack of relapse for ≥ 4 years prior to DMT discontinuation.⁵ Though these patients still may have been classified as RRMS, both these independent predictors for stability postdiscontinuation of DMTs are the typical characteristics of a nonactive SPMS patient.

Pathophysiology may help explain why DMT discontinuation seems to produce no adverse clinical outcomes in people with nonactive SPMS. Nonactive SPMS, which follows after RRMS, is largely correlated with age. In nonactive SPMS, there is less B and T lymphocyte migration across the blood-brain barrier. Furthermore, a lifetime of low-grade inflammation during the RRMS phase results in axonal damage and declined repair capacity, which produces the predominance of neurodegeneration in the nonactive SPMS disease process.⁶ This pathophysiologic difference between active and nonactive disease not only explains the different symptomatology of these MS subtypes, but also could explain why drugs that target the inflammatory processes more characteristic of active disease are not effective in nonactive SPMS.

Other recent studies explored the impact of age on DMT efficacy for patients with nonactive SPMS. A meta-analysis by Weidman and colleagues pooled trial data across multiple DMT classes in > 28,000 patients.⁷ The resulting regression model predicted zero efficacy of any DMT in patients who are aged > 53 years. High-efficacy DMTs only outperformed low-efficacy DMTs in people aged < 40.5 years. Another observational study by Hua and colleagues saw a similar result.⁸ This study included patients who discontinued DMT who were aged ≥ 60 years. The median follow-up time was 5.3 years. Of the 178 patients who discontinued DMTs, only 1 patient had a relapse. In this study, the age for participation provided a higher likelihood that patients included were in nonactive SPMS. Furthermore, the outcome reflects the typical presentation of nonactive SPMS where, despite the continuation or discontinuation of DMT, there was a lack of relapses. When comparing patients who discontinued DMTs with those who continued use, there was no significant difference in their 25-foot walk times, which is an objective marker for a more progressive symptom seen in nonactive MS.

The DISCOMS trial (NCT03073603) has been completed, but full results are not yet published. In this noninferiority trial, > 250 patients aged ≥ 55 years were assessed on a variety of outcomes, including relapses, EDSS score, and QOL. MS subtypes were considered at baseline, and subgroup analysis looking particularly at the SPMS population could provide further insight into its effect on MS course.

Quality of Life

Whether discontinuation of DMTs is worth considering in nonactive SPMS, it is also important to consider the risks and burdens associated with continuation. Medication administration burdens come with all MS DMTs whether there is the need to inject oneself, increased pill burden, or travel to an infusion clinic. The ever-rising costs of DMTs also can be a financial burden to the patient.⁹ All MS DMTs carry risks of adverse effects (AEs). These can range from a mild injection site reaction to severe infection, depending on the DMT used. Many of these severe AEs, such as opportunistic infections and cancer, have been associated with either an increased risk of occurrence and/or worsened outcomes in older adults who remain on DMTs, particularly moderate- to high-efficacy DMTs, such as sphingosine-1- phosphate receptor modulators, fumarates, natalizumab, alemtuzumab, cladribine, and anti-CD20 antibodies.¹⁰ In a 2019 survey of 377 patients with MS, 63.8% of respondents ranked safety as the most important reason they would consider discontinuing their DMTs.¹¹ In addition, a real-world study comparing people with nonactive SPMS who continued DMTs vs those who discontinued found that discontinuers reported better QOL.⁸

Conversation Guide for Discontinuing Therapies

The 2019 survey that assessed reasons for discontinuation also asked people with nonactive SPMS whether they thought they were in a nonactive disease stage, and what was their likelihood they would stop DMTs.¹¹ Interestingly, only 59.4% of respondents self-assessed their MS as nonactive, and just 11.9% of respondents were willing to discontinue DMTs.¹¹ These results suggest that there may be a need for patient education about nonactive SPMS and the rationale to continue or discontinue DMTs. Thus, before broaching the topic of discontinuation, explaining the nonactive SPMS subtype is important.

Even with a good understanding of nonactive SPMS, patients may be hesitant to stop using DMTs that they previously relied on to keep their MS stable. The 2019 survey ranked physician recommendation as the third highest reason to discontinue DMTs.¹¹ Taking the time to explain the clinical evidence for DMT discontinuation may help patients better understand a clinician’s recommendation and inspire more confidence.

Another important aspect of DMT discontinuation decision making is creating a plan for how the patient will be monitored to provide assurance if they experience a relapse. The 2019 survey asked patients what would be most important to them for their management plan after discontinuing DMT; magnetic resonance imaging and neurologic examination monitoring ranked the highest.¹¹ The plan should include timing for follow-up appointments and imaging, providing the patient comfort in knowing their MS will be monitored and verified for the relapse stability that is expected from nonactive SPMS. In the rare case a relapse does occur, having a contingency plan and noting the possibility of restarting DMTs is an integral part of reassuring the patient that their decision to discontinue DMTs will be treated with the utmost caution and individualized to their needs.

Lastly, highlighting which aspects of MS treatment will continue to be a priority in nonactive SPMS, such as symptomatic medication management and nonpharmacologic therapy, is important for the patient to recognize that there are still opportunities to manage this phase of MS. There are many lifestyle modifications that can be considered complementary to medical management of MS at any stage of the disease. Vascular comorbidities, such as hypertension, hyperlipidemia, and diabetes, have been associated with more rapid disability progression in MS.¹² Optimized management of these diseases may slow disability progression, in addition to the benefit of improved outcomes of the vascular comorbidity. Various formats of exercise have been studied in the MS population. A meta-analysis of aerobic, resistance, and combined exercise found benefits in these formats on health-related QOL.¹³

Many dietary strategies have been studied in MS. A recent network meta-analysis reviewed some of the more commonly studied diets, including low-fat, modified Mediterranean, ketogenic, anti-inflammatory, Paleolithic, intermittent fasting, and calorie restriction vs a usual diet.¹⁴ Although the overall quality of evidence was low, the Paleolithic and modified Mediterranean showed greater reductions in fatigue, as well as increased physical and mental QOL compared with a usual diet. The low-fat diet was associated with a reduction in fatigue. Many of these lifestyle modifications may complement optimized vascular comorbidity treatment; however, any exercise regimen or dietary change should be considered with the whole health of the patient in mind.

As with any health care decision, it is important to involve the patient in a joint decision regarding their care. This may mean giving the patient time to think about the information presented, do their own research, talk to family members or other clinicians, etc. The decision to discontinue DMT may not happen at the same appointment it is initially brought up at. It may even be reasonable to revisit the conversation later if discontinuation is not something the patient is amenable to at the time.

Conclusions

There is high-quality evidence that discontinuing DMTs in nonactive SPMS is not a major detriment to the MS disease course. Current literature also suggests that there may be benefits to discontinuation in this MS subtype in terms of QOL and meeting patient values. Additional research particularly in the nonactive SPMS population will continue to improve the knowledge and awareness of this aspect of MS DMT management. The growing evidence in this area may make discontinuation of DMT in nonactive SPMS a less-debatable topic, but it is still a major treatment decision that clinicians must thoroughly discuss with the patient to provide high-quality, patient-centered care.

A duodenocaval fistula (DCF) is seen when a connection exists between the duodenum and the inferior vena cava. It is a rare entity that is commonly missed and presents a diagnostic challenge due to its nonspecific presenting symptoms.^1,2 Patients commonly present with gastrointestinal (GI) bleeding or sepsis. Here we present a case of a 37-year-old man who presented to the hospital for a workup related to melena but went into cardiac arrest prior to an esophagogastroduodenoscopy. Unfortunately, on autopsy, the patient was found to have a DCF. We highlight the diagnostic challenge associated with DCF and how in this case the presentation was confused by a diagnosis of possible transfusion-related acute lung injury (TRALI). To the best of our knowledge, this is also the first description of a case of DCF associated with food embolism to the lungs causing respiratory failure.

Case Presentation

A 37-year-old man with a history significant for bulimia presented to the hospital with a 3-day history of melena and reports of dizziness. The patient did not report being on any prescribed medications but noted that he took 4 aspirin daily to “calm his nerves.” The rest of the patient’s history was unremarkable aside from a reported history of induced emesis 3 to 4 times per week for an extended period up until 2 weeks before admission.

On admission, his vital signs demonstrated tachycardia and orthostatic hypotension. Pertinent findings on physical examination were skin pallor, a normal lung examination, mild epigastric tenderness, and guaiac-positive stools. He was alert and oriented to person, place, and time with no focal deficits. His admission laboratory tests were notable for a hemoglobin (Hb) level of 4.6 g/dL (reference range, 14-17.9), a white blood cell count of 13.5 K/cm (reference range, 4.5-11), an international normalized ratio of 1.21, a blood urea nitrogen of 61 mg/dL (reference range, 10-20), and a creatinine of 2.3 mg/dL (reference range, 0.8-1.4). The patient was placed on 2 L of oxygen via nasal cannula for comfort rather than true hypoxia. A chest X-ray on admission was negative with no signs of infiltrate, edema, or widened mediastinum. An abdominal X-ray was significant for a dilated stomach consistent with bulimia with no abdominal free air or signs of obstruction. The case was discussed with the gastroenterology service who felt that the patient needed to be more hemodynamically stable before pursuing endoscopic evaluation.

He was admitted to the intensive care unit and give a transfusion of 4 units of fresh frozen plasma and 2 packed red blood cells (PRBCs) without any issues. During the infusion of a third PRBC, he developed chills, tachycardia, and hypertension with accompanying respiratory distress characterized by wheezing, decreased breath sounds bilaterally, and a decrease in oxygen saturation to 70% on 2 L supplemental oxygen. He responded to treatment with meperidine, methylprednisolone sodium succinate, albuterol nebulizer, and acetaminophen. A new chest X-ray was read as “development of pulmonary edema vs bilateral pneumonitis.” A transfusion reaction was reported to the blood bank and a diagnosis of TRALI was considered. That evening, he completed a dose of platelets and another PRBC without difficulty after he was premedicated with meperidine, methylprednisolone sodium succinate, and acetaminophen. During the night, the patient spiked a temperature of 40.3 °C that was successfully treated with a cooling blanket and acetaminophen.

The following morning the patient was found to be tachypneic and tachycardic with his face mask off. His symptoms were corrected by replacing his face mask. He claimed he felt anxious about getting more transfusions and that he had breathing problems like this at home in the recent past. The patient requested an aspirin to calm his nerves. Over the course of the day, his Hb level dropped from 6.6 g/dL to 5.9 g/dL, and 2 washed leukopoor PRBCs were ordered.

The first unit was infused uneventfully, but after 125 cc of the second unit, the patient developed respiratory distress, rigors, and hypotension to 70/58 mm Hg despite premedication. He again was treated successfully with increased face mask support. A few rales were noted, but his fluid balance was even. A second transfusion reaction was filed with the blood bank and based on the 2 transfusion-associated events with no other clear explanation for his symptoms, the clinical team favored the TRALI diagnosis. However, the blood bank was suspicious this might not be TRALI as the previous night the patient had 2 episodes of respiratory distress with drops in oxygen saturation unassociated with transfusions. The patient was clinically stable for the remainder of the night.

Early the following morning the patient was scheduled for an esophagogastroduodenoscopy to evaluate for a source of his bleeding. At the beginning of the procedure, a unit of washed leukoreduced PRBCs was hung for a Hb level of 6.9 g/dL. No bleeding source was noted in the stomach, but as the endoscope was passed into the duodenum, and after an infusion of only 25 cc of RBCs, the patient became cyanotic and went into cardiac arrest. Despite advanced resuscitation efforts over 90 minutes, the patient could not be successfully resuscitated and died while in the endoscopy suite. A transfusion reaction workup was initiated but was unremarkable. The transfusion medicine staff was suspicious that something other than TRALI was the cause of the patient’s respiratory distress as he had respiratory distress remote to the transfusions and the unit was prepared correctly before administration. The patient’s family agreed to an autopsy.

Pathology

A full autopsy was performed 22 hours after the patient died. The lungs were congested and of increased weight: The right lung was 800 g, and the left was 750 g. The right lower lobe had a wedge-shaped infarction measuring 6 cm × 5 cm fed by a thrombosed vessel. Multiple small hemorrhagic wedge-shaped areas were noted in the left lung. An ulcer measuring 6 cm × 5 cm was noted just distal to the pylorus. At the base of this ulcer was a 1.5 cm × 0.5 cm tract that communicated with the inferior vena cava (Figure 1).

A postmortem blood culture was positive for Clostridium perfringens (C perfringens) and Candida albicans (C Albicans). Interestingly, one of the collected blood culture vials exploded en route to the laboratory, presumably due to the presence of many gas-forming C perfringens bacteria.

On microscopic examination of the autopsy samples, gram-positive rods were observed in the tissue of multiple organs, including the heart, lungs, liver, and kidneys (Figure 2).

Serology

Fourteen days after the patient’s death, both PRBC units infused during transfusion reactions were positive for granulocyte antibodies by immunofluorescence and agglutination techniques. Human leukocyte antigen antibody testing was also sent but was not found in either the donor or patient.

Discussion

Our case illustrates the unique and challenging diagnosis of DCF given the rarity of presentation and how quickly patients may clinically decompensate. After an extensive search of the medical literature, we were only able to identify about 40 previous cases of DCF, of which 37 were described in one review.¹ DCF, although rare, should be considered at risk for forming in the following settings: migrating inferior vena cava filter, right nephrectomy and radiotherapy, duodenal peptic ulcer, abdominal trauma, and oncologic settings involving metastatic malignancy requiring radiation and/or surgical grafting of the inferior vena cava.^1-4 When the diagnosis is considered, computed tomography (CT) is the best initial imaging modality as it allows for noninvasive evaluation of both the inferior vena cava and nonadjacent structures. A commonality of our case and those described in the literature is the diagnostic mystery and nonspecific symptoms patients present with, thus making CT an appropriate diagnostic modality. Endoscopy is useful for the further workup of GI bleeding and the diagnosis of peptic ulcer disease.⁵ In our case, given the patient’s autopsy findings and history of extensive nonsteroidal anti-inflammatory drug use, the duodenal peptic ulcer was likely the precipitating factor for his DCF.

The most challenging aspect in diagnosing DCF is that many times patients present with nonspecific symptoms, and given its rarity it is not something that is usually at the forefront of most differentials.² This diagnostic difficulty may elucidate why there is such a relatively high mortality rate—nearly 40%—associated with DCF and why many times accurate diagnosis is not made until autopsy.^1,3 The most common presenting manifestations are sepsis and/or GI bleeding; in less than half the cases described in the literature patients had both sepsis and GI bleeding. In our case, the patient had signs of melena but was not felt to be septic as his presenting signs were felt to be in the setting of blood loss and dehydration (given his history of bulimia), not an acute infectious source.

In retrospect, one of the more confounding aspects of this case is the clinical picture concerning for TRALI. The patient required supplemental oxygen throughout his hospitalization and decompensated while or after receiving a transfusion, thus having TRALI on the differential was not felt inappropriate at that time. However, this case also illustrates the power of an anchoring bias, and perhaps the clinical team anchored on the diagnosis of TRALI too quickly before considering other possible etiologies for the patient’s respiratory distress. TRALI can be one of the most challenging diagnoses to make in the field of transfusion medicine as there are no definitive diagnostic criteria.⁶ It is felt to be a clinical diagnosis of exclusion as there is no pathognomonic sign or diagnostic test to confirm it as the cause of the patient’s respiratory distress, though anti–human leukocyte antigen antibodies commonly are present.^6,7 Considering how quickly the patient decompensated on day 2 of hospitalization and the presence of C perfringens bacteremia, which carries a mortality rate of 27% to 44%, it is likely that further diagnostic workup would not have changed the clinical outcome.⁸

Conclusions

Our investigation reports a case of a DCF in the setting of significant duodenal peptic ulcer disease. We highlight the diagnostic challenge that this commonly lethal etiology presents. We believe ours is the first case in which it was confused for TRALI and associated with food embolism to the lungs causing hypoxic respiratory failure. We want to highlight that DCF, though rare, should be considered for patients who present with GI bleeding and hypoxic respiratory failure.

A duodenocaval fistula (DCF) is seen when a connection exists between the duodenum and the inferior vena cava. It is a rare entity that is commonly missed and presents a diagnostic challenge due to its nonspecific presenting symptoms.^1,2 Patients commonly present with gastrointestinal (GI) bleeding or sepsis. Here we present a case of a 37-year-old man who presented to the hospital for a workup related to melena but went into cardiac arrest prior to an esophagogastroduodenoscopy. Unfortunately, on autopsy, the patient was found to have a DCF. We highlight the diagnostic challenge associated with DCF and how in this case the presentation was confused by a diagnosis of possible transfusion-related acute lung injury (TRALI). To the best of our knowledge, this is also the first description of a case of DCF associated with food embolism to the lungs causing respiratory failure.

Case Presentation

A 37-year-old man with a history significant for bulimia presented to the hospital with a 3-day history of melena and reports of dizziness. The patient did not report being on any prescribed medications but noted that he took 4 aspirin daily to “calm his nerves.” The rest of the patient’s history was unremarkable aside from a reported history of induced emesis 3 to 4 times per week for an extended period up until 2 weeks before admission.

On admission, his vital signs demonstrated tachycardia and orthostatic hypotension. Pertinent findings on physical examination were skin pallor, a normal lung examination, mild epigastric tenderness, and guaiac-positive stools. He was alert and oriented to person, place, and time with no focal deficits. His admission laboratory tests were notable for a hemoglobin (Hb) level of 4.6 g/dL (reference range, 14-17.9), a white blood cell count of 13.5 K/cm (reference range, 4.5-11), an international normalized ratio of 1.21, a blood urea nitrogen of 61 mg/dL (reference range, 10-20), and a creatinine of 2.3 mg/dL (reference range, 0.8-1.4). The patient was placed on 2 L of oxygen via nasal cannula for comfort rather than true hypoxia. A chest X-ray on admission was negative with no signs of infiltrate, edema, or widened mediastinum. An abdominal X-ray was significant for a dilated stomach consistent with bulimia with no abdominal free air or signs of obstruction. The case was discussed with the gastroenterology service who felt that the patient needed to be more hemodynamically stable before pursuing endoscopic evaluation.

He was admitted to the intensive care unit and give a transfusion of 4 units of fresh frozen plasma and 2 packed red blood cells (PRBCs) without any issues. During the infusion of a third PRBC, he developed chills, tachycardia, and hypertension with accompanying respiratory distress characterized by wheezing, decreased breath sounds bilaterally, and a decrease in oxygen saturation to 70% on 2 L supplemental oxygen. He responded to treatment with meperidine, methylprednisolone sodium succinate, albuterol nebulizer, and acetaminophen. A new chest X-ray was read as “development of pulmonary edema vs bilateral pneumonitis.” A transfusion reaction was reported to the blood bank and a diagnosis of TRALI was considered. That evening, he completed a dose of platelets and another PRBC without difficulty after he was premedicated with meperidine, methylprednisolone sodium succinate, and acetaminophen. During the night, the patient spiked a temperature of 40.3 °C that was successfully treated with a cooling blanket and acetaminophen.

The following morning the patient was found to be tachypneic and tachycardic with his face mask off. His symptoms were corrected by replacing his face mask. He claimed he felt anxious about getting more transfusions and that he had breathing problems like this at home in the recent past. The patient requested an aspirin to calm his nerves. Over the course of the day, his Hb level dropped from 6.6 g/dL to 5.9 g/dL, and 2 washed leukopoor PRBCs were ordered.

The first unit was infused uneventfully, but after 125 cc of the second unit, the patient developed respiratory distress, rigors, and hypotension to 70/58 mm Hg despite premedication. He again was treated successfully with increased face mask support. A few rales were noted, but his fluid balance was even. A second transfusion reaction was filed with the blood bank and based on the 2 transfusion-associated events with no other clear explanation for his symptoms, the clinical team favored the TRALI diagnosis. However, the blood bank was suspicious this might not be TRALI as the previous night the patient had 2 episodes of respiratory distress with drops in oxygen saturation unassociated with transfusions. The patient was clinically stable for the remainder of the night.

Early the following morning the patient was scheduled for an esophagogastroduodenoscopy to evaluate for a source of his bleeding. At the beginning of the procedure, a unit of washed leukoreduced PRBCs was hung for a Hb level of 6.9 g/dL. No bleeding source was noted in the stomach, but as the endoscope was passed into the duodenum, and after an infusion of only 25 cc of RBCs, the patient became cyanotic and went into cardiac arrest. Despite advanced resuscitation efforts over 90 minutes, the patient could not be successfully resuscitated and died while in the endoscopy suite. A transfusion reaction workup was initiated but was unremarkable. The transfusion medicine staff was suspicious that something other than TRALI was the cause of the patient’s respiratory distress as he had respiratory distress remote to the transfusions and the unit was prepared correctly before administration. The patient’s family agreed to an autopsy.

Pathology

A full autopsy was performed 22 hours after the patient died. The lungs were congested and of increased weight: The right lung was 800 g, and the left was 750 g. The right lower lobe had a wedge-shaped infarction measuring 6 cm × 5 cm fed by a thrombosed vessel. Multiple small hemorrhagic wedge-shaped areas were noted in the left lung. An ulcer measuring 6 cm × 5 cm was noted just distal to the pylorus. At the base of this ulcer was a 1.5 cm × 0.5 cm tract that communicated with the inferior vena cava (Figure 1).

A postmortem blood culture was positive for Clostridium perfringens (C perfringens) and Candida albicans (C Albicans). Interestingly, one of the collected blood culture vials exploded en route to the laboratory, presumably due to the presence of many gas-forming C perfringens bacteria.

On microscopic examination of the autopsy samples, gram-positive rods were observed in the tissue of multiple organs, including the heart, lungs, liver, and kidneys (Figure 2).

Serology

Fourteen days after the patient’s death, both PRBC units infused during transfusion reactions were positive for granulocyte antibodies by immunofluorescence and agglutination techniques. Human leukocyte antigen antibody testing was also sent but was not found in either the donor or patient.

Discussion

Our case illustrates the unique and challenging diagnosis of DCF given the rarity of presentation and how quickly patients may clinically decompensate. After an extensive search of the medical literature, we were only able to identify about 40 previous cases of DCF, of which 37 were described in one review.¹ DCF, although rare, should be considered at risk for forming in the following settings: migrating inferior vena cava filter, right nephrectomy and radiotherapy, duodenal peptic ulcer, abdominal trauma, and oncologic settings involving metastatic malignancy requiring radiation and/or surgical grafting of the inferior vena cava.^1-4 When the diagnosis is considered, computed tomography (CT) is the best initial imaging modality as it allows for noninvasive evaluation of both the inferior vena cava and nonadjacent structures. A commonality of our case and those described in the literature is the diagnostic mystery and nonspecific symptoms patients present with, thus making CT an appropriate diagnostic modality. Endoscopy is useful for the further workup of GI bleeding and the diagnosis of peptic ulcer disease.⁵ In our case, given the patient’s autopsy findings and history of extensive nonsteroidal anti-inflammatory drug use, the duodenal peptic ulcer was likely the precipitating factor for his DCF.

The most challenging aspect in diagnosing DCF is that many times patients present with nonspecific symptoms, and given its rarity it is not something that is usually at the forefront of most differentials.² This diagnostic difficulty may elucidate why there is such a relatively high mortality rate—nearly 40%—associated with DCF and why many times accurate diagnosis is not made until autopsy.^1,3 The most common presenting manifestations are sepsis and/or GI bleeding; in less than half the cases described in the literature patients had both sepsis and GI bleeding. In our case, the patient had signs of melena but was not felt to be septic as his presenting signs were felt to be in the setting of blood loss and dehydration (given his history of bulimia), not an acute infectious source.

In retrospect, one of the more confounding aspects of this case is the clinical picture concerning for TRALI. The patient required supplemental oxygen throughout his hospitalization and decompensated while or after receiving a transfusion, thus having TRALI on the differential was not felt inappropriate at that time. However, this case also illustrates the power of an anchoring bias, and perhaps the clinical team anchored on the diagnosis of TRALI too quickly before considering other possible etiologies for the patient’s respiratory distress. TRALI can be one of the most challenging diagnoses to make in the field of transfusion medicine as there are no definitive diagnostic criteria.⁶ It is felt to be a clinical diagnosis of exclusion as there is no pathognomonic sign or diagnostic test to confirm it as the cause of the patient’s respiratory distress, though anti–human leukocyte antigen antibodies commonly are present.^6,7 Considering how quickly the patient decompensated on day 2 of hospitalization and the presence of C perfringens bacteremia, which carries a mortality rate of 27% to 44%, it is likely that further diagnostic workup would not have changed the clinical outcome.⁸

Conclusions

Our investigation reports a case of a DCF in the setting of significant duodenal peptic ulcer disease. We highlight the diagnostic challenge that this commonly lethal etiology presents. We believe ours is the first case in which it was confused for TRALI and associated with food embolism to the lungs causing hypoxic respiratory failure. We want to highlight that DCF, though rare, should be considered for patients who present with GI bleeding and hypoxic respiratory failure.

A duodenocaval fistula (DCF) is seen when a connection exists between the duodenum and the inferior vena cava. It is a rare entity that is commonly missed and presents a diagnostic challenge due to its nonspecific presenting symptoms.^1,2 Patients commonly present with gastrointestinal (GI) bleeding or sepsis. Here we present a case of a 37-year-old man who presented to the hospital for a workup related to melena but went into cardiac arrest prior to an esophagogastroduodenoscopy. Unfortunately, on autopsy, the patient was found to have a DCF. We highlight the diagnostic challenge associated with DCF and how in this case the presentation was confused by a diagnosis of possible transfusion-related acute lung injury (TRALI). To the best of our knowledge, this is also the first description of a case of DCF associated with food embolism to the lungs causing respiratory failure.

Case Presentation

A 37-year-old man with a history significant for bulimia presented to the hospital with a 3-day history of melena and reports of dizziness. The patient did not report being on any prescribed medications but noted that he took 4 aspirin daily to “calm his nerves.” The rest of the patient’s history was unremarkable aside from a reported history of induced emesis 3 to 4 times per week for an extended period up until 2 weeks before admission.

On admission, his vital signs demonstrated tachycardia and orthostatic hypotension. Pertinent findings on physical examination were skin pallor, a normal lung examination, mild epigastric tenderness, and guaiac-positive stools. He was alert and oriented to person, place, and time with no focal deficits. His admission laboratory tests were notable for a hemoglobin (Hb) level of 4.6 g/dL (reference range, 14-17.9), a white blood cell count of 13.5 K/cm (reference range, 4.5-11), an international normalized ratio of 1.21, a blood urea nitrogen of 61 mg/dL (reference range, 10-20), and a creatinine of 2.3 mg/dL (reference range, 0.8-1.4). The patient was placed on 2 L of oxygen via nasal cannula for comfort rather than true hypoxia. A chest X-ray on admission was negative with no signs of infiltrate, edema, or widened mediastinum. An abdominal X-ray was significant for a dilated stomach consistent with bulimia with no abdominal free air or signs of obstruction. The case was discussed with the gastroenterology service who felt that the patient needed to be more hemodynamically stable before pursuing endoscopic evaluation.

He was admitted to the intensive care unit and give a transfusion of 4 units of fresh frozen plasma and 2 packed red blood cells (PRBCs) without any issues. During the infusion of a third PRBC, he developed chills, tachycardia, and hypertension with accompanying respiratory distress characterized by wheezing, decreased breath sounds bilaterally, and a decrease in oxygen saturation to 70% on 2 L supplemental oxygen. He responded to treatment with meperidine, methylprednisolone sodium succinate, albuterol nebulizer, and acetaminophen. A new chest X-ray was read as “development of pulmonary edema vs bilateral pneumonitis.” A transfusion reaction was reported to the blood bank and a diagnosis of TRALI was considered. That evening, he completed a dose of platelets and another PRBC without difficulty after he was premedicated with meperidine, methylprednisolone sodium succinate, and acetaminophen. During the night, the patient spiked a temperature of 40.3 °C that was successfully treated with a cooling blanket and acetaminophen.

The following morning the patient was found to be tachypneic and tachycardic with his face mask off. His symptoms were corrected by replacing his face mask. He claimed he felt anxious about getting more transfusions and that he had breathing problems like this at home in the recent past. The patient requested an aspirin to calm his nerves. Over the course of the day, his Hb level dropped from 6.6 g/dL to 5.9 g/dL, and 2 washed leukopoor PRBCs were ordered.

The first unit was infused uneventfully, but after 125 cc of the second unit, the patient developed respiratory distress, rigors, and hypotension to 70/58 mm Hg despite premedication. He again was treated successfully with increased face mask support. A few rales were noted, but his fluid balance was even. A second transfusion reaction was filed with the blood bank and based on the 2 transfusion-associated events with no other clear explanation for his symptoms, the clinical team favored the TRALI diagnosis. However, the blood bank was suspicious this might not be TRALI as the previous night the patient had 2 episodes of respiratory distress with drops in oxygen saturation unassociated with transfusions. The patient was clinically stable for the remainder of the night.

Early the following morning the patient was scheduled for an esophagogastroduodenoscopy to evaluate for a source of his bleeding. At the beginning of the procedure, a unit of washed leukoreduced PRBCs was hung for a Hb level of 6.9 g/dL. No bleeding source was noted in the stomach, but as the endoscope was passed into the duodenum, and after an infusion of only 25 cc of RBCs, the patient became cyanotic and went into cardiac arrest. Despite advanced resuscitation efforts over 90 minutes, the patient could not be successfully resuscitated and died while in the endoscopy suite. A transfusion reaction workup was initiated but was unremarkable. The transfusion medicine staff was suspicious that something other than TRALI was the cause of the patient’s respiratory distress as he had respiratory distress remote to the transfusions and the unit was prepared correctly before administration. The patient’s family agreed to an autopsy.

Pathology

A full autopsy was performed 22 hours after the patient died. The lungs were congested and of increased weight: The right lung was 800 g, and the left was 750 g. The right lower lobe had a wedge-shaped infarction measuring 6 cm × 5 cm fed by a thrombosed vessel. Multiple small hemorrhagic wedge-shaped areas were noted in the left lung. An ulcer measuring 6 cm × 5 cm was noted just distal to the pylorus. At the base of this ulcer was a 1.5 cm × 0.5 cm tract that communicated with the inferior vena cava (Figure 1).

A postmortem blood culture was positive for Clostridium perfringens (C perfringens) and Candida albicans (C Albicans). Interestingly, one of the collected blood culture vials exploded en route to the laboratory, presumably due to the presence of many gas-forming C perfringens bacteria.

On microscopic examination of the autopsy samples, gram-positive rods were observed in the tissue of multiple organs, including the heart, lungs, liver, and kidneys (Figure 2).

Serology

Fourteen days after the patient’s death, both PRBC units infused during transfusion reactions were positive for granulocyte antibodies by immunofluorescence and agglutination techniques. Human leukocyte antigen antibody testing was also sent but was not found in either the donor or patient.

Discussion

Our case illustrates the unique and challenging diagnosis of DCF given the rarity of presentation and how quickly patients may clinically decompensate. After an extensive search of the medical literature, we were only able to identify about 40 previous cases of DCF, of which 37 were described in one review.¹ DCF, although rare, should be considered at risk for forming in the following settings: migrating inferior vena cava filter, right nephrectomy and radiotherapy, duodenal peptic ulcer, abdominal trauma, and oncologic settings involving metastatic malignancy requiring radiation and/or surgical grafting of the inferior vena cava.^1-4 When the diagnosis is considered, computed tomography (CT) is the best initial imaging modality as it allows for noninvasive evaluation of both the inferior vena cava and nonadjacent structures. A commonality of our case and those described in the literature is the diagnostic mystery and nonspecific symptoms patients present with, thus making CT an appropriate diagnostic modality. Endoscopy is useful for the further workup of GI bleeding and the diagnosis of peptic ulcer disease.⁵ In our case, given the patient’s autopsy findings and history of extensive nonsteroidal anti-inflammatory drug use, the duodenal peptic ulcer was likely the precipitating factor for his DCF.

The most challenging aspect in diagnosing DCF is that many times patients present with nonspecific symptoms, and given its rarity it is not something that is usually at the forefront of most differentials.² This diagnostic difficulty may elucidate why there is such a relatively high mortality rate—nearly 40%—associated with DCF and why many times accurate diagnosis is not made until autopsy.^1,3 The most common presenting manifestations are sepsis and/or GI bleeding; in less than half the cases described in the literature patients had both sepsis and GI bleeding. In our case, the patient had signs of melena but was not felt to be septic as his presenting signs were felt to be in the setting of blood loss and dehydration (given his history of bulimia), not an acute infectious source.

In retrospect, one of the more confounding aspects of this case is the clinical picture concerning for TRALI. The patient required supplemental oxygen throughout his hospitalization and decompensated while or after receiving a transfusion, thus having TRALI on the differential was not felt inappropriate at that time. However, this case also illustrates the power of an anchoring bias, and perhaps the clinical team anchored on the diagnosis of TRALI too quickly before considering other possible etiologies for the patient’s respiratory distress. TRALI can be one of the most challenging diagnoses to make in the field of transfusion medicine as there are no definitive diagnostic criteria.⁶ It is felt to be a clinical diagnosis of exclusion as there is no pathognomonic sign or diagnostic test to confirm it as the cause of the patient’s respiratory distress, though anti–human leukocyte antigen antibodies commonly are present.^6,7 Considering how quickly the patient decompensated on day 2 of hospitalization and the presence of C perfringens bacteremia, which carries a mortality rate of 27% to 44%, it is likely that further diagnostic workup would not have changed the clinical outcome.⁸

Conclusions

Our investigation reports a case of a DCF in the setting of significant duodenal peptic ulcer disease. We highlight the diagnostic challenge that this commonly lethal etiology presents. We believe ours is the first case in which it was confused for TRALI and associated with food embolism to the lungs causing hypoxic respiratory failure. We want to highlight that DCF, though rare, should be considered for patients who present with GI bleeding and hypoxic respiratory failure.