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Life in the woods
“I went to the woods because I wished to live deliberately, to front only the essential facts of life, and see if I could not learn what it had to teach.” – Henry David Thoreau
I have many patients like Maxine. Tall, with a shock of white hair. Old, but still in charge. When you try to make eye contact, she looks right through you. First with her left eye. Then her right. Her face is inscrutable. What’s she thinking? Unlike many of my patients, however, this Maxine was a llama. Every morning my daughter and I tried to coax her into moving as we leaned on the cold steel gate that kept her in her pasture. We were visiting family in October and chose to stay on a working New England farm. The kids will love the animals, we thought, and we’ll appreciate the extra bedrooms.
Airbnb helped us find this charming fiber-farm in Rhode Island where they raise Leicester Longwool sheep, a historic breed that once roamed George Washington’s pastures, along with a few goats, ducks, chickens, and Maxine. It’s situated deep in the woods, which were yellow, orange, and red that week. As it happens, we were just a short drive due south of Walden Pond where Henry David Thoreau spent 2 years, 2 months and 2 days escaping “overcivilization” nearly 175 years ago. Hoisting our overweight bags over the uneven granite stone steps when we arrived, I realized this was going to be more like the Thoreau experiment than I intended. The farmhouse dated to the 1790s. There were wide, creaky floorboards, low ceilings, one staircase to the bedrooms (which could have aptly been called a ladder) and loads of book-laden shelves. Instructions posted in the kitchen warned that the heat is tricky to regulate – a redundant admonition as we watched our 3-year-old putting on her socks and shoes as she got into bed.
Now, if you’ve ever been on vacation with little kids, you know that it’s basically just childcare in a novel location. After barricading the staircase with luggage and unplugging lamps from their dicey outlets we set out to feed the chickens and try to pet a sheep. Walking the perimeter of the farm we saw stone walls that needed mending and stumbled across two ancient cemeteries, one had been for family, the other for slaves. I wondered how many farmers and weavers and menders had walked this trail with their kids over the generations.
The next morning, we learned that roosters do not in fact crow at dawn, they crow before dawn (which could also aptly be called nighttime). There were no commutes or late patients here. But there was work to be done. Chickens don’t care that it’s Sunday. It downpoured. Watching the sheep from the kitchen as I sipped my coffee, they didn’t seem to mind. Nor did our farmer hosts who trudged past them in tall boots, just as they had every other day of their farmer lives.
By the fifth day, we had fallen into the rhythms of the homestead. We cracked the blue, green, and brown eggs that our hosts placed outside our door in the early hours and made omelets that were as orange as the foliage. We finally learned to adjust the heat so we neither got chilblains nor had to open the windows and strip naked to cool down. The sky was a brilliant blue that last morning and Sloan ran around trying to catch leaves as they blew off the trees. She had no objective. No counting. No contest. Just chasing leaves as they fell. It was the ultimate atelic activity, done just for doing it. I joined her and found I was no better at this than a 3-year-old.
We might all benefit from a little time in the woods.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“I went to the woods because I wished to live deliberately, to front only the essential facts of life, and see if I could not learn what it had to teach.” – Henry David Thoreau
I have many patients like Maxine. Tall, with a shock of white hair. Old, but still in charge. When you try to make eye contact, she looks right through you. First with her left eye. Then her right. Her face is inscrutable. What’s she thinking? Unlike many of my patients, however, this Maxine was a llama. Every morning my daughter and I tried to coax her into moving as we leaned on the cold steel gate that kept her in her pasture. We were visiting family in October and chose to stay on a working New England farm. The kids will love the animals, we thought, and we’ll appreciate the extra bedrooms.
Airbnb helped us find this charming fiber-farm in Rhode Island where they raise Leicester Longwool sheep, a historic breed that once roamed George Washington’s pastures, along with a few goats, ducks, chickens, and Maxine. It’s situated deep in the woods, which were yellow, orange, and red that week. As it happens, we were just a short drive due south of Walden Pond where Henry David Thoreau spent 2 years, 2 months and 2 days escaping “overcivilization” nearly 175 years ago. Hoisting our overweight bags over the uneven granite stone steps when we arrived, I realized this was going to be more like the Thoreau experiment than I intended. The farmhouse dated to the 1790s. There were wide, creaky floorboards, low ceilings, one staircase to the bedrooms (which could have aptly been called a ladder) and loads of book-laden shelves. Instructions posted in the kitchen warned that the heat is tricky to regulate – a redundant admonition as we watched our 3-year-old putting on her socks and shoes as she got into bed.
Now, if you’ve ever been on vacation with little kids, you know that it’s basically just childcare in a novel location. After barricading the staircase with luggage and unplugging lamps from their dicey outlets we set out to feed the chickens and try to pet a sheep. Walking the perimeter of the farm we saw stone walls that needed mending and stumbled across two ancient cemeteries, one had been for family, the other for slaves. I wondered how many farmers and weavers and menders had walked this trail with their kids over the generations.
The next morning, we learned that roosters do not in fact crow at dawn, they crow before dawn (which could also aptly be called nighttime). There were no commutes or late patients here. But there was work to be done. Chickens don’t care that it’s Sunday. It downpoured. Watching the sheep from the kitchen as I sipped my coffee, they didn’t seem to mind. Nor did our farmer hosts who trudged past them in tall boots, just as they had every other day of their farmer lives.
By the fifth day, we had fallen into the rhythms of the homestead. We cracked the blue, green, and brown eggs that our hosts placed outside our door in the early hours and made omelets that were as orange as the foliage. We finally learned to adjust the heat so we neither got chilblains nor had to open the windows and strip naked to cool down. The sky was a brilliant blue that last morning and Sloan ran around trying to catch leaves as they blew off the trees. She had no objective. No counting. No contest. Just chasing leaves as they fell. It was the ultimate atelic activity, done just for doing it. I joined her and found I was no better at this than a 3-year-old.
We might all benefit from a little time in the woods.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“I went to the woods because I wished to live deliberately, to front only the essential facts of life, and see if I could not learn what it had to teach.” – Henry David Thoreau
I have many patients like Maxine. Tall, with a shock of white hair. Old, but still in charge. When you try to make eye contact, she looks right through you. First with her left eye. Then her right. Her face is inscrutable. What’s she thinking? Unlike many of my patients, however, this Maxine was a llama. Every morning my daughter and I tried to coax her into moving as we leaned on the cold steel gate that kept her in her pasture. We were visiting family in October and chose to stay on a working New England farm. The kids will love the animals, we thought, and we’ll appreciate the extra bedrooms.
Airbnb helped us find this charming fiber-farm in Rhode Island where they raise Leicester Longwool sheep, a historic breed that once roamed George Washington’s pastures, along with a few goats, ducks, chickens, and Maxine. It’s situated deep in the woods, which were yellow, orange, and red that week. As it happens, we were just a short drive due south of Walden Pond where Henry David Thoreau spent 2 years, 2 months and 2 days escaping “overcivilization” nearly 175 years ago. Hoisting our overweight bags over the uneven granite stone steps when we arrived, I realized this was going to be more like the Thoreau experiment than I intended. The farmhouse dated to the 1790s. There were wide, creaky floorboards, low ceilings, one staircase to the bedrooms (which could have aptly been called a ladder) and loads of book-laden shelves. Instructions posted in the kitchen warned that the heat is tricky to regulate – a redundant admonition as we watched our 3-year-old putting on her socks and shoes as she got into bed.
Now, if you’ve ever been on vacation with little kids, you know that it’s basically just childcare in a novel location. After barricading the staircase with luggage and unplugging lamps from their dicey outlets we set out to feed the chickens and try to pet a sheep. Walking the perimeter of the farm we saw stone walls that needed mending and stumbled across two ancient cemeteries, one had been for family, the other for slaves. I wondered how many farmers and weavers and menders had walked this trail with their kids over the generations.
The next morning, we learned that roosters do not in fact crow at dawn, they crow before dawn (which could also aptly be called nighttime). There were no commutes or late patients here. But there was work to be done. Chickens don’t care that it’s Sunday. It downpoured. Watching the sheep from the kitchen as I sipped my coffee, they didn’t seem to mind. Nor did our farmer hosts who trudged past them in tall boots, just as they had every other day of their farmer lives.
By the fifth day, we had fallen into the rhythms of the homestead. We cracked the blue, green, and brown eggs that our hosts placed outside our door in the early hours and made omelets that were as orange as the foliage. We finally learned to adjust the heat so we neither got chilblains nor had to open the windows and strip naked to cool down. The sky was a brilliant blue that last morning and Sloan ran around trying to catch leaves as they blew off the trees. She had no objective. No counting. No contest. Just chasing leaves as they fell. It was the ultimate atelic activity, done just for doing it. I joined her and found I was no better at this than a 3-year-old.
We might all benefit from a little time in the woods.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
How to develop a patient referral program
Here is how old I am: When I graduated from medical school in 1977, marketing was prohibited. It was the legal profession that challenged the ban on advertising by professionals, leading to a landmark Supreme Court decision (Bates v State Bar of Arizona, 1977), which opened the door to marketing in the legal and medical professions.
Since then, Strategies range from the basic Internet website through postings on the major social media sites, and occasionally to larger-budget campaigns involving local radio, television, or billboard advertising.
All these methods are effective, to varying degrees; but nothing provides as much benefit – relative to its comparatively low cost – as the original marketing tool, word-of-mouth patient referrals. According to one survey, a clear majority of Americans still consider word-of-mouth recommendations to be the most influential element driving purchase decisions. Of course, some of your new patients already come from such referrals; but you can get a lot more by actively encouraging your existing patients to sing your praises, rather than waiting for them to do it on their own.
Soliciting current patients for referrals does take a little planning, structure, and a basic understanding of exactly how patient referral programs work. When executed correctly, a patient referral program can add substantial growth to your practice at minimal cost.
Your first step, as with any new project, should be to identify your goals: Clearly define what kind of patients you are looking to attract. Do you want more patients for cosmetic procedures, medical treatment, skin cancer screenings, a specific diagnosis (such as psoriasis), or a general mix? Design your announcements, brochures, and other literature (more on that in a minute) with those goals in mind.
Next, identify any applicable federal or state laws that dictate what you can and cannot legally do to encourage such referrals. It might be tempting, for example, to offer discounts on future services for successful referrals; but some medical groups frown on it, some states prohibit it, and the Federal Anti-Kickback Statute makes it illegal to pay anyone to refer Medicare or Medicaid patients to you if you file a claim for your services. In my experience, most patients are happy to recommend someone whom they believe provides excellent care to a friend or relative without any sort of monetary incentive; but if you plan to offer a material reward of any kind, run it by your attorney first.
Once your legal ducks are in order, make patients aware that you are accepting new patients and would welcome referrals by posting notices to that effect around your office and on your website and social media pages. Outline exactly what sort of patients (based on your goals, above) you are looking for, how to refer someone, whom to contact, and what kind of information is needed. Make it clear why existing patients should refer someone to your practice. Remind them of your specialized training, advanced technology, and patient-focused approach to health care. Highlight the benefits of the program and encourage your patients to participate.
Before implementation, you will need to educate your employees about the referral program and its benefits. All staff members should understand the program and be able to answer basic questions about it from patients or referring professionals. Encourage staffers to actively promote the program during patient interactions.
Then, start making some decisions. How, specifically, will you be requesting referrals in the office? Many physicians are not comfortable asking patients themselves. If you are going to let your assistants or receptionists do it, you will need to write a script for them to follow. An example of a basic script might be, “If you are happy with the care you are receiving here, we would love for you to tell your friends and family about us.” Your staff can then hand out cards, brochures, or both to reinforce the message, and perhaps send a follow-up email to remind them.
A referral system isn’t worth the effort if you don’t know whether it is working. Establish a system to track and monitor referrals. This could be as simple as a spreadsheet or purchasing a more sophisticated software program. Ensure that you can accurately identify and credit the referring patients for their referrals.
Make sure to thank referring patients with a thank-you note or email. Expressing gratitude will encourage continued participation in the program.
A successful referral program does not happen overnight. It relies on providing exceptional patient care and building strong relationships with your existing patients. By implementing such a program, you can leverage the satisfaction and loyalty of your patients to attract new patients and grow your private practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Here is how old I am: When I graduated from medical school in 1977, marketing was prohibited. It was the legal profession that challenged the ban on advertising by professionals, leading to a landmark Supreme Court decision (Bates v State Bar of Arizona, 1977), which opened the door to marketing in the legal and medical professions.
Since then, Strategies range from the basic Internet website through postings on the major social media sites, and occasionally to larger-budget campaigns involving local radio, television, or billboard advertising.
All these methods are effective, to varying degrees; but nothing provides as much benefit – relative to its comparatively low cost – as the original marketing tool, word-of-mouth patient referrals. According to one survey, a clear majority of Americans still consider word-of-mouth recommendations to be the most influential element driving purchase decisions. Of course, some of your new patients already come from such referrals; but you can get a lot more by actively encouraging your existing patients to sing your praises, rather than waiting for them to do it on their own.
Soliciting current patients for referrals does take a little planning, structure, and a basic understanding of exactly how patient referral programs work. When executed correctly, a patient referral program can add substantial growth to your practice at minimal cost.
Your first step, as with any new project, should be to identify your goals: Clearly define what kind of patients you are looking to attract. Do you want more patients for cosmetic procedures, medical treatment, skin cancer screenings, a specific diagnosis (such as psoriasis), or a general mix? Design your announcements, brochures, and other literature (more on that in a minute) with those goals in mind.
Next, identify any applicable federal or state laws that dictate what you can and cannot legally do to encourage such referrals. It might be tempting, for example, to offer discounts on future services for successful referrals; but some medical groups frown on it, some states prohibit it, and the Federal Anti-Kickback Statute makes it illegal to pay anyone to refer Medicare or Medicaid patients to you if you file a claim for your services. In my experience, most patients are happy to recommend someone whom they believe provides excellent care to a friend or relative without any sort of monetary incentive; but if you plan to offer a material reward of any kind, run it by your attorney first.
Once your legal ducks are in order, make patients aware that you are accepting new patients and would welcome referrals by posting notices to that effect around your office and on your website and social media pages. Outline exactly what sort of patients (based on your goals, above) you are looking for, how to refer someone, whom to contact, and what kind of information is needed. Make it clear why existing patients should refer someone to your practice. Remind them of your specialized training, advanced technology, and patient-focused approach to health care. Highlight the benefits of the program and encourage your patients to participate.
Before implementation, you will need to educate your employees about the referral program and its benefits. All staff members should understand the program and be able to answer basic questions about it from patients or referring professionals. Encourage staffers to actively promote the program during patient interactions.
Then, start making some decisions. How, specifically, will you be requesting referrals in the office? Many physicians are not comfortable asking patients themselves. If you are going to let your assistants or receptionists do it, you will need to write a script for them to follow. An example of a basic script might be, “If you are happy with the care you are receiving here, we would love for you to tell your friends and family about us.” Your staff can then hand out cards, brochures, or both to reinforce the message, and perhaps send a follow-up email to remind them.
A referral system isn’t worth the effort if you don’t know whether it is working. Establish a system to track and monitor referrals. This could be as simple as a spreadsheet or purchasing a more sophisticated software program. Ensure that you can accurately identify and credit the referring patients for their referrals.
Make sure to thank referring patients with a thank-you note or email. Expressing gratitude will encourage continued participation in the program.
A successful referral program does not happen overnight. It relies on providing exceptional patient care and building strong relationships with your existing patients. By implementing such a program, you can leverage the satisfaction and loyalty of your patients to attract new patients and grow your private practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Here is how old I am: When I graduated from medical school in 1977, marketing was prohibited. It was the legal profession that challenged the ban on advertising by professionals, leading to a landmark Supreme Court decision (Bates v State Bar of Arizona, 1977), which opened the door to marketing in the legal and medical professions.
Since then, Strategies range from the basic Internet website through postings on the major social media sites, and occasionally to larger-budget campaigns involving local radio, television, or billboard advertising.
All these methods are effective, to varying degrees; but nothing provides as much benefit – relative to its comparatively low cost – as the original marketing tool, word-of-mouth patient referrals. According to one survey, a clear majority of Americans still consider word-of-mouth recommendations to be the most influential element driving purchase decisions. Of course, some of your new patients already come from such referrals; but you can get a lot more by actively encouraging your existing patients to sing your praises, rather than waiting for them to do it on their own.
Soliciting current patients for referrals does take a little planning, structure, and a basic understanding of exactly how patient referral programs work. When executed correctly, a patient referral program can add substantial growth to your practice at minimal cost.
Your first step, as with any new project, should be to identify your goals: Clearly define what kind of patients you are looking to attract. Do you want more patients for cosmetic procedures, medical treatment, skin cancer screenings, a specific diagnosis (such as psoriasis), or a general mix? Design your announcements, brochures, and other literature (more on that in a minute) with those goals in mind.
Next, identify any applicable federal or state laws that dictate what you can and cannot legally do to encourage such referrals. It might be tempting, for example, to offer discounts on future services for successful referrals; but some medical groups frown on it, some states prohibit it, and the Federal Anti-Kickback Statute makes it illegal to pay anyone to refer Medicare or Medicaid patients to you if you file a claim for your services. In my experience, most patients are happy to recommend someone whom they believe provides excellent care to a friend or relative without any sort of monetary incentive; but if you plan to offer a material reward of any kind, run it by your attorney first.
Once your legal ducks are in order, make patients aware that you are accepting new patients and would welcome referrals by posting notices to that effect around your office and on your website and social media pages. Outline exactly what sort of patients (based on your goals, above) you are looking for, how to refer someone, whom to contact, and what kind of information is needed. Make it clear why existing patients should refer someone to your practice. Remind them of your specialized training, advanced technology, and patient-focused approach to health care. Highlight the benefits of the program and encourage your patients to participate.
Before implementation, you will need to educate your employees about the referral program and its benefits. All staff members should understand the program and be able to answer basic questions about it from patients or referring professionals. Encourage staffers to actively promote the program during patient interactions.
Then, start making some decisions. How, specifically, will you be requesting referrals in the office? Many physicians are not comfortable asking patients themselves. If you are going to let your assistants or receptionists do it, you will need to write a script for them to follow. An example of a basic script might be, “If you are happy with the care you are receiving here, we would love for you to tell your friends and family about us.” Your staff can then hand out cards, brochures, or both to reinforce the message, and perhaps send a follow-up email to remind them.
A referral system isn’t worth the effort if you don’t know whether it is working. Establish a system to track and monitor referrals. This could be as simple as a spreadsheet or purchasing a more sophisticated software program. Ensure that you can accurately identify and credit the referring patients for their referrals.
Make sure to thank referring patients with a thank-you note or email. Expressing gratitude will encourage continued participation in the program.
A successful referral program does not happen overnight. It relies on providing exceptional patient care and building strong relationships with your existing patients. By implementing such a program, you can leverage the satisfaction and loyalty of your patients to attract new patients and grow your private practice.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
The future of medicine is RNA
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Every once in a while, medicine changes in a fundamental way, and we may not realize it while it’s happening. I wasn’t around in 1928 when Fleming discovered penicillin; or in 1953 when Watson, Crick, and Franklin characterized the double-helical structure of DNA.
But looking at medicine today, there are essentially two places where I think we will see, in retrospect, that we were at a fundamental turning point. One is artificial intelligence, which gets so much attention and hype that I will simply say yes, this will change things, stay tuned.
The other is a bit more obscure, but I suspect it may be just as impactful. That other thing is 
I want to start with the idea that many diseases are, fundamentally, a problem of proteins. In some cases, like hypercholesterolemia, the body produces too much protein; in others, like hemophilia, too little.
When you think about disease this way, you realize that our current medications take effect late in the disease game. We have these molecules that try to block a protein from its receptor, prevent a protein from cleaving another protein, or increase the rate that a protein is broken down. It’s all distal to the fundamental problem: the production of the bad protein in the first place.
Enter small inhibitory RNAs, or siRNAs for short, discovered in 1998 by Andrew Fire and Craig Mello at UMass Worcester. The two won the Nobel prize in medicine just 8 years later; that’s a really short time, highlighting just how important this discovery was. In contrast, Karikó and Weissman won the Nobel for mRNA vaccines this year, after inventing them 18 years ago.
siRNAs are the body’s way of targeting proteins for destruction before they are ever created. About 20 base pairs long, siRNAs seek out a complementary target mRNA, attach to it, and call in a group of proteins to destroy it. With the target mRNA gone, no protein can be created.
You see where this is going, right? How does high cholesterol kill you? Proteins. How does Staphylococcus aureus kill you? Proteins. Even viruses can’t replicate if their RNA is prevented from being turned into proteins.
So, how do we use siRNAs? A new paper appearing in JAMA describes a fairly impressive use case.
The background here is that higher levels of lipoprotein(a), an LDL-like protein, are associated with cardiovascular disease, heart attack, and stroke. But unfortunately, statins really don’t have any effect on lipoprotein(a) levels. Neither does diet. Your lipoprotein(a) level seems to be more or less hard-coded genetically.
So, what if we stop the genetic machinery from working? Enter lepodisiran, a drug from Eli Lilly. Unlike so many other medications, which are usually found in nature, purified, and synthesized, lepodisiran was created from scratch. It’s not hard. Thanks to the Human Genome Project, we know the genetic code for lipoprotein(a), so inventing an siRNA to target it specifically is trivial. That’s one of the key features of siRNA – you don’t have to find a chemical that binds strongly to some protein receptor, and worry about the off-target effects and all that nonsense. You just pick a protein you want to suppress and you suppress it.
Okay, it’s not that simple. siRNA is broken down very quickly by the body, so it needs to be targeted to the organ of interest – in this case, the liver, since that is where lipoprotein(a) is synthesized. Lepodisiran is targeted to the liver by this special targeting label here.
The report is a standard dose-escalation trial. Six patients, all with elevated lipoprotein(a) levels, were started with a 4-mg dose (two additional individuals got placebo). They were intensely monitored, spending 3 days in a research unit for multiple blood draws followed by weekly, and then biweekly outpatient visits. Once they had done well, the next group of six people received a higher dose (two more got placebo), and the process was repeated – six times total – until the highest dose, 608 mg, was reached.
This is an injection, of course; siRNA wouldn’t withstand the harshness of the digestive system. And it’s only one injection. You can see from the blood concentration curves that within about 48 hours, circulating lepodisiran was not detectable.
But check out these results. Remember, this is from a single injection of lepodisiran.
Lipoprotein(a) levels start to drop within a week of administration, and they stay down. In the higher-dose groups, levels are nearly undetectable a year after that injection.
It was this graph that made me sit back and think that there might be something new under the sun. A single injection that can suppress protein synthesis for an entire year? If it really works, it changes the game.
Of course, this study wasn’t powered to look at important outcomes like heart attacks and strokes. It was primarily designed to assess safety, and the drug was pretty well tolerated, with similar rates of adverse events in the drug and placebo groups.
As crazy as it sounds, the real concern here might be that this drug is too good; is it safe to drop your lipoprotein(a) levels to zero for a year? I don’t know. But lower doses don’t have quite as strong an effect.
Trust me, these drugs are going to change things. They already are. In July, The New England Journal of Medicine published a study of zilebesiran, an siRNA that inhibits the production of angiotensinogen, to control blood pressure. Similar story: One injection led to a basically complete suppression of angiotensinogen and a sustained decrease in blood pressure.
I’m not exaggerating when I say that there may come a time when you go to your doctor once a year, get your RNA shots, and don’t have to take any other medication from that point on. And that time may be, like, 5 years from now. It’s wild.
Seems to me that that rapid Nobel Prize was very well deserved.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Every once in a while, medicine changes in a fundamental way, and we may not realize it while it’s happening. I wasn’t around in 1928 when Fleming discovered penicillin; or in 1953 when Watson, Crick, and Franklin characterized the double-helical structure of DNA.
But looking at medicine today, there are essentially two places where I think we will see, in retrospect, that we were at a fundamental turning point. One is artificial intelligence, which gets so much attention and hype that I will simply say yes, this will change things, stay tuned.
The other is a bit more obscure, but I suspect it may be just as impactful. That other thing is
I want to start with the idea that many diseases are, fundamentally, a problem of proteins. In some cases, like hypercholesterolemia, the body produces too much protein; in others, like hemophilia, too little.
When you think about disease this way, you realize that our current medications take effect late in the disease game. We have these molecules that try to block a protein from its receptor, prevent a protein from cleaving another protein, or increase the rate that a protein is broken down. It’s all distal to the fundamental problem: the production of the bad protein in the first place.
Enter small inhibitory RNAs, or siRNAs for short, discovered in 1998 by Andrew Fire and Craig Mello at UMass Worcester. The two won the Nobel prize in medicine just 8 years later; that’s a really short time, highlighting just how important this discovery was. In contrast, Karikó and Weissman won the Nobel for mRNA vaccines this year, after inventing them 18 years ago.
siRNAs are the body’s way of targeting proteins for destruction before they are ever created. About 20 base pairs long, siRNAs seek out a complementary target mRNA, attach to it, and call in a group of proteins to destroy it. With the target mRNA gone, no protein can be created.
You see where this is going, right? How does high cholesterol kill you? Proteins. How does Staphylococcus aureus kill you? Proteins. Even viruses can’t replicate if their RNA is prevented from being turned into proteins.
So, how do we use siRNAs? A new paper appearing in JAMA describes a fairly impressive use case.
The background here is that higher levels of lipoprotein(a), an LDL-like protein, are associated with cardiovascular disease, heart attack, and stroke. But unfortunately, statins really don’t have any effect on lipoprotein(a) levels. Neither does diet. Your lipoprotein(a) level seems to be more or less hard-coded genetically.
So, what if we stop the genetic machinery from working? Enter lepodisiran, a drug from Eli Lilly. Unlike so many other medications, which are usually found in nature, purified, and synthesized, lepodisiran was created from scratch. It’s not hard. Thanks to the Human Genome Project, we know the genetic code for lipoprotein(a), so inventing an siRNA to target it specifically is trivial. That’s one of the key features of siRNA – you don’t have to find a chemical that binds strongly to some protein receptor, and worry about the off-target effects and all that nonsense. You just pick a protein you want to suppress and you suppress it.
Okay, it’s not that simple. siRNA is broken down very quickly by the body, so it needs to be targeted to the organ of interest – in this case, the liver, since that is where lipoprotein(a) is synthesized. Lepodisiran is targeted to the liver by this special targeting label here.
The report is a standard dose-escalation trial. Six patients, all with elevated lipoprotein(a) levels, were started with a 4-mg dose (two additional individuals got placebo). They were intensely monitored, spending 3 days in a research unit for multiple blood draws followed by weekly, and then biweekly outpatient visits. Once they had done well, the next group of six people received a higher dose (two more got placebo), and the process was repeated – six times total – until the highest dose, 608 mg, was reached.
This is an injection, of course; siRNA wouldn’t withstand the harshness of the digestive system. And it’s only one injection. You can see from the blood concentration curves that within about 48 hours, circulating lepodisiran was not detectable.
But check out these results. Remember, this is from a single injection of lepodisiran.
Lipoprotein(a) levels start to drop within a week of administration, and they stay down. In the higher-dose groups, levels are nearly undetectable a year after that injection.
It was this graph that made me sit back and think that there might be something new under the sun. A single injection that can suppress protein synthesis for an entire year? If it really works, it changes the game.
Of course, this study wasn’t powered to look at important outcomes like heart attacks and strokes. It was primarily designed to assess safety, and the drug was pretty well tolerated, with similar rates of adverse events in the drug and placebo groups.
As crazy as it sounds, the real concern here might be that this drug is too good; is it safe to drop your lipoprotein(a) levels to zero for a year? I don’t know. But lower doses don’t have quite as strong an effect.
Trust me, these drugs are going to change things. They already are. In July, The New England Journal of Medicine published a study of zilebesiran, an siRNA that inhibits the production of angiotensinogen, to control blood pressure. Similar story: One injection led to a basically complete suppression of angiotensinogen and a sustained decrease in blood pressure.
I’m not exaggerating when I say that there may come a time when you go to your doctor once a year, get your RNA shots, and don’t have to take any other medication from that point on. And that time may be, like, 5 years from now. It’s wild.
Seems to me that that rapid Nobel Prize was very well deserved.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Every once in a while, medicine changes in a fundamental way, and we may not realize it while it’s happening. I wasn’t around in 1928 when Fleming discovered penicillin; or in 1953 when Watson, Crick, and Franklin characterized the double-helical structure of DNA.
But looking at medicine today, there are essentially two places where I think we will see, in retrospect, that we were at a fundamental turning point. One is artificial intelligence, which gets so much attention and hype that I will simply say yes, this will change things, stay tuned.
The other is a bit more obscure, but I suspect it may be just as impactful. That other thing is
I want to start with the idea that many diseases are, fundamentally, a problem of proteins. In some cases, like hypercholesterolemia, the body produces too much protein; in others, like hemophilia, too little.
When you think about disease this way, you realize that our current medications take effect late in the disease game. We have these molecules that try to block a protein from its receptor, prevent a protein from cleaving another protein, or increase the rate that a protein is broken down. It’s all distal to the fundamental problem: the production of the bad protein in the first place.
Enter small inhibitory RNAs, or siRNAs for short, discovered in 1998 by Andrew Fire and Craig Mello at UMass Worcester. The two won the Nobel prize in medicine just 8 years later; that’s a really short time, highlighting just how important this discovery was. In contrast, Karikó and Weissman won the Nobel for mRNA vaccines this year, after inventing them 18 years ago.
siRNAs are the body’s way of targeting proteins for destruction before they are ever created. About 20 base pairs long, siRNAs seek out a complementary target mRNA, attach to it, and call in a group of proteins to destroy it. With the target mRNA gone, no protein can be created.
You see where this is going, right? How does high cholesterol kill you? Proteins. How does Staphylococcus aureus kill you? Proteins. Even viruses can’t replicate if their RNA is prevented from being turned into proteins.
So, how do we use siRNAs? A new paper appearing in JAMA describes a fairly impressive use case.
The background here is that higher levels of lipoprotein(a), an LDL-like protein, are associated with cardiovascular disease, heart attack, and stroke. But unfortunately, statins really don’t have any effect on lipoprotein(a) levels. Neither does diet. Your lipoprotein(a) level seems to be more or less hard-coded genetically.
So, what if we stop the genetic machinery from working? Enter lepodisiran, a drug from Eli Lilly. Unlike so many other medications, which are usually found in nature, purified, and synthesized, lepodisiran was created from scratch. It’s not hard. Thanks to the Human Genome Project, we know the genetic code for lipoprotein(a), so inventing an siRNA to target it specifically is trivial. That’s one of the key features of siRNA – you don’t have to find a chemical that binds strongly to some protein receptor, and worry about the off-target effects and all that nonsense. You just pick a protein you want to suppress and you suppress it.
Okay, it’s not that simple. siRNA is broken down very quickly by the body, so it needs to be targeted to the organ of interest – in this case, the liver, since that is where lipoprotein(a) is synthesized. Lepodisiran is targeted to the liver by this special targeting label here.
The report is a standard dose-escalation trial. Six patients, all with elevated lipoprotein(a) levels, were started with a 4-mg dose (two additional individuals got placebo). They were intensely monitored, spending 3 days in a research unit for multiple blood draws followed by weekly, and then biweekly outpatient visits. Once they had done well, the next group of six people received a higher dose (two more got placebo), and the process was repeated – six times total – until the highest dose, 608 mg, was reached.
This is an injection, of course; siRNA wouldn’t withstand the harshness of the digestive system. And it’s only one injection. You can see from the blood concentration curves that within about 48 hours, circulating lepodisiran was not detectable.
But check out these results. Remember, this is from a single injection of lepodisiran.
Lipoprotein(a) levels start to drop within a week of administration, and they stay down. In the higher-dose groups, levels are nearly undetectable a year after that injection.
It was this graph that made me sit back and think that there might be something new under the sun. A single injection that can suppress protein synthesis for an entire year? If it really works, it changes the game.
Of course, this study wasn’t powered to look at important outcomes like heart attacks and strokes. It was primarily designed to assess safety, and the drug was pretty well tolerated, with similar rates of adverse events in the drug and placebo groups.
As crazy as it sounds, the real concern here might be that this drug is too good; is it safe to drop your lipoprotein(a) levels to zero for a year? I don’t know. But lower doses don’t have quite as strong an effect.
Trust me, these drugs are going to change things. They already are. In July, The New England Journal of Medicine published a study of zilebesiran, an siRNA that inhibits the production of angiotensinogen, to control blood pressure. Similar story: One injection led to a basically complete suppression of angiotensinogen and a sustained decrease in blood pressure.
I’m not exaggerating when I say that there may come a time when you go to your doctor once a year, get your RNA shots, and don’t have to take any other medication from that point on. And that time may be, like, 5 years from now. It’s wild.
Seems to me that that rapid Nobel Prize was very well deserved.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.
A version of this article appeared on Medscape.com.
Mental health characteristics of refugee children
Since 1983, when I was a child and fled as a boat refugee from Vietnam with my mother, the international plight of displaced people has only worsened. From 1997 to 2022, the number of forcibly displaced people has more than tripled, growing from 34 million to more than 108 million.1
Displaced people are designated as refugees only when they cross international borders and meet the United Nations High Commissioner for Refugees’ (UNHCR) definition as “persons outside their countries of origin who are in need of international protection because of a serious threat to their life, physical integrity, or freedom in their country of origin as a result of persecution, armed conflict, violence, or serious public disorder.”2 There is a separate mandate by the United Nations for the aid of Palestinian refugees under the United Nations General Assembly’s United Nations Relief and Works Agency for Palestinian Refugees in the Near East (UNRWA).3 Of the displaced in 2022, more than 36 million were recognized as refugees under UNHCR and UNRWA mandates.1 Of these, almost 50% were children, at 17.5 million.4 To make matters worse, worldwide children represent less than one-third of the population.4 Since 2022, the increase in refugeeism is mostly driven by Ukraine and Syria, though also significantly Afghanistan, Venezuela, Sudan, Myanmar, Congo, Somalia, and Central African Republic.4 Refugeeism is a growing problem that disproportionately impacts children through sheer number, and one suspects, given their greater overall vulnerabilities compared with adults, physical and mental health consequences.
Traumas of refugees compared with non-refugee immigrants
In terms of mental health, refugees are distinct from non-refugee immigrants in that they likely experience more severe psychosocial adversities from greater poverty, greater risk of family separation, and uncertainty of the asylum process.5-8
From my own experience, this stems from the urgent nature of the refugee’s displacement, where they are often fleeing an immediate danger. My family had fled persecution from Communist forces and the social economic collapse that rendered Vietnam, for a time, one of the poorest in the world.9 Or, as my mother observed, “We had to leave because even doctors were starving.”
Refugees often have little preparation, have little legal protection since they are often criminalized, and are forced to endure dangerous conditions where they are vulnerable to smugglers and criminals who exploit their unprotected status. Once they arrive in their new country, they often do not have other family as social supports or resources. They themselves become the anchor for future legal and orderly immigration of their remaining family, given that they can extend their refugee status to those left behind.10 These non-refugee immigrants, unlike their refugee counterparts, are often flown to their new homes with more preparation, protecting them from dangerous conditions, and have the benefit of family who provide them with resources. As such, refugees tend to experience more traumatic life events than non-refugee immigrants. This was true in my family where those of us who initially escaped became the anchors to legally, and more safely, immigrate most of our family in Vietnam. We became their resources, likely making their acclimation smoother.
The mental health of refugee children and their caregivers
It is important to understand the stressors affecting the caregivers of children, since effective treatment of their mental health conditions can also benefit the children as well.11 In fact, among the greatest protective factors for refugee children is the presence of an adult caregiver, suggesting that the child’s mental health is dependent on the caregivers.
Those children who are separated show much worse mental health sequalae.12 As such, an understanding of the caregiver’s stressors is important. For example, when we were escaping Vietnam, my mom would protect me from our hardships by talking about our goals in America, minimizing our dangers by saying that we would be rewarded with things like a hamburger with its seemingly impossible amount of meat. Physically, my mother would always sleep with her arms around me and a knife hidden in order to ward off any attackers at night. When I was starving in the hull of a boat, having not eaten for days, my mother begged for food and gave me what she could get. And post-escape, my family focused on work and applied for aid for shelter and food, while encouraging us to invest in education, likely preventing involvement in criminal activities or gangs. Though overall, my family shielded me from the worst consequences, they also passed on their fears. One of my uncles had been killed by the police when he tried to escape, and so my family passed down a deep suspicion of authorities, whether they were the police or school principals. My mother had vivid memories of Communist re-education camps, which likely gave her a lasting fear that a Communist would find out our identities in America and re-capture us.
The mental health risk of refugees
Given that refugees tend to experience greater amounts of traumatic life events and a vast array of stressors sustained across years and even decades before, during, and after migration, it is no wonder they have much higher rates of mental health conditions, most predominantly PTSD and affective disorders.13,14 They are at particular risk of developing psychoses because they are more likely to experience a range of physical, psychological, and psychosocial problems associated with adversities such as violence, discrimination, economic stress, and social isolation.13 For example, the period leading up to my escape consisted of decades of prolonged war: the French-Indochina from 1945 to 1954, then the Vietnam War from 1955 to 1975) as well as the persecution and re-education camps afterward. What my family had to endure created a period of fear and loss into which I was born into in 1976. That year, my family had lost its fortune due to the Communist government seizing of our home and business, plunging us from a comfortable middle- to upper-class life to poverty. There was also widespread fear of systematic rape by the Communist victors. So my family endured great stress and the loss of a way of life leading up to our escape.
For the refugees, the escape itself is often a dangerous journey where, given its emergent nature, they are often exposed to the elements. We know about the current situation in Ukraine and Gaza, where children are fleeing from bombs and bullets. In my situation, we endured weeks of starvation crammed in the hull of boat as we forged through the Indian Ocean to the Philippines. One of my aunts, on a separate trip, perished because her boat had capsized, like so many others. Though impossible to verify, it has been estimated that up to 70% of Vietnamese refugees died during their escape.15 After the boat, my mother and I still had to brave Malaysian jungles and prisons, and then refugee camps for a year before we reached safety at an American Embassy in the Philippines. After we gained sponsorship to America, the traumas did not abate, but were only replaced by those of culture shock, poverty, and alienation. Taken by themselves, significant traumas exist in each phase of a refugee child’s escape, whether before, during, or after. These traumas are likely compounded since they are continuously layered and sustained across years, even decades. They affect not only the children, but their parents, and sometimes even a whole nation of people.
Summary
Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, or social upheavals. It is known that refugees are at greater risk for PTSD and affective and psychotic disorders, presumably due to increased traumatic life events before, during, and after their migration. The writer uses his own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.
Dr. Nguyen is a second year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.
References
1. UNHCR. Global Trends. Forced displacement in 2016. Geneva, Switzerland: The UN Refugee Agency, 2022. https://www.unhcr.org/global-trends.
2. Office of the United Nations High Commissioner for Refugees. The refugee concept under international law. Global compact for safe, orderly and regular migration. https://www.unhcr.org/sites/
3. United Nations. (2023, November 11). The Question of Palestine. Un.org. https://www.un.org/unispal/document/un-general-assembly-renews-unrwa-mandate-press-release/
4. UNICEF. (2023, November 11). Child displacement. Data.unicef.org. https://data.unicef.org/topic/child-migration-and-displacement/displacement
5. Kinzie JD. Immigrants and refugees: The psychiatric perspective. Transcult Psychiatry. 2006 Dec;43(4):577-91. doi: 10.1177/1363461506070782.
6. Eaton W and Harrison G. Ethnic disadvantage and schizophrenia. Acta Psychiatr Scand Suppl. 2000:(407):38-43. doi: 10.1034/j.1600-0447.2000.00007.x.
7. Gilliver SC et al. Recent research on the mental health of immigrants to Sweden: a literature review. Eur J Public Health. 2014 Aug:24 Suppl 1:72-9. doi: 10.1093/eurpub/cku101.
8. Rapp MA et al. When local poverty is more important than your income: Mental health in minorities in inner cities. World Psychiatry. 2015 Jun;14(2):249-50. doi: 10.1002/wps.20221.
9. Cima, Ronald, ed. Vietnam: A Country Study. Washington: GPO for the Library of Congress, 1987.
10. United States Citizenship & Immigration Services (2023, November 12). Refugees. Uscis.gov. https://www.uscis.gov/humanitarian/refugees-and-asylum/refugees
11. Fazel M and Betancourt TS. (2018). Preventive mental health interventions for refugee children and adolescents in high-income settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-32. doi: 10.1016/S2352-4642(17)30147-5.
12. Fazel M et al. Mental health of displaced and refugee children resettled in high-income countries: risk and protective factors. Lancet. 2012 Jan 21;379(9812):266-82. doi: 10.1016/S0140-6736(11)60051-2.
13. Dapunt J et al. Refugees and psychosis: A review of the literature. Transl Psychiatry. 2017 Jun 13;7(6):e1149. doi: 10.1038/tp.2017.119.
14. Fazel M et al. Prevalence of serious mental disorder in 7,000 refugees resettled in western countries: a systematic review. Lancet. 2005 Apr;365(9467):1309-14. doi: 10.1016/S0140-6736(05)61027-6.
15. Rummel R. Statistics of Vietnamese Democide, in his Statistics of Democide. 1997. Table 6.1B,lines 730, 749-51.
Since 1983, when I was a child and fled as a boat refugee from Vietnam with my mother, the international plight of displaced people has only worsened. From 1997 to 2022, the number of forcibly displaced people has more than tripled, growing from 34 million to more than 108 million.1
Displaced people are designated as refugees only when they cross international borders and meet the United Nations High Commissioner for Refugees’ (UNHCR) definition as “persons outside their countries of origin who are in need of international protection because of a serious threat to their life, physical integrity, or freedom in their country of origin as a result of persecution, armed conflict, violence, or serious public disorder.”2 There is a separate mandate by the United Nations for the aid of Palestinian refugees under the United Nations General Assembly’s United Nations Relief and Works Agency for Palestinian Refugees in the Near East (UNRWA).3 Of the displaced in 2022, more than 36 million were recognized as refugees under UNHCR and UNRWA mandates.1 Of these, almost 50% were children, at 17.5 million.4 To make matters worse, worldwide children represent less than one-third of the population.4 Since 2022, the increase in refugeeism is mostly driven by Ukraine and Syria, though also significantly Afghanistan, Venezuela, Sudan, Myanmar, Congo, Somalia, and Central African Republic.4 Refugeeism is a growing problem that disproportionately impacts children through sheer number, and one suspects, given their greater overall vulnerabilities compared with adults, physical and mental health consequences.
Traumas of refugees compared with non-refugee immigrants
In terms of mental health, refugees are distinct from non-refugee immigrants in that they likely experience more severe psychosocial adversities from greater poverty, greater risk of family separation, and uncertainty of the asylum process.5-8
From my own experience, this stems from the urgent nature of the refugee’s displacement, where they are often fleeing an immediate danger. My family had fled persecution from Communist forces and the social economic collapse that rendered Vietnam, for a time, one of the poorest in the world.9 Or, as my mother observed, “We had to leave because even doctors were starving.”
Refugees often have little preparation, have little legal protection since they are often criminalized, and are forced to endure dangerous conditions where they are vulnerable to smugglers and criminals who exploit their unprotected status. Once they arrive in their new country, they often do not have other family as social supports or resources. They themselves become the anchor for future legal and orderly immigration of their remaining family, given that they can extend their refugee status to those left behind.10 These non-refugee immigrants, unlike their refugee counterparts, are often flown to their new homes with more preparation, protecting them from dangerous conditions, and have the benefit of family who provide them with resources. As such, refugees tend to experience more traumatic life events than non-refugee immigrants. This was true in my family where those of us who initially escaped became the anchors to legally, and more safely, immigrate most of our family in Vietnam. We became their resources, likely making their acclimation smoother.
The mental health of refugee children and their caregivers
It is important to understand the stressors affecting the caregivers of children, since effective treatment of their mental health conditions can also benefit the children as well.11 In fact, among the greatest protective factors for refugee children is the presence of an adult caregiver, suggesting that the child’s mental health is dependent on the caregivers.
Those children who are separated show much worse mental health sequalae.12 As such, an understanding of the caregiver’s stressors is important. For example, when we were escaping Vietnam, my mom would protect me from our hardships by talking about our goals in America, minimizing our dangers by saying that we would be rewarded with things like a hamburger with its seemingly impossible amount of meat. Physically, my mother would always sleep with her arms around me and a knife hidden in order to ward off any attackers at night. When I was starving in the hull of a boat, having not eaten for days, my mother begged for food and gave me what she could get. And post-escape, my family focused on work and applied for aid for shelter and food, while encouraging us to invest in education, likely preventing involvement in criminal activities or gangs. Though overall, my family shielded me from the worst consequences, they also passed on their fears. One of my uncles had been killed by the police when he tried to escape, and so my family passed down a deep suspicion of authorities, whether they were the police or school principals. My mother had vivid memories of Communist re-education camps, which likely gave her a lasting fear that a Communist would find out our identities in America and re-capture us.
The mental health risk of refugees
Given that refugees tend to experience greater amounts of traumatic life events and a vast array of stressors sustained across years and even decades before, during, and after migration, it is no wonder they have much higher rates of mental health conditions, most predominantly PTSD and affective disorders.13,14 They are at particular risk of developing psychoses because they are more likely to experience a range of physical, psychological, and psychosocial problems associated with adversities such as violence, discrimination, economic stress, and social isolation.13 For example, the period leading up to my escape consisted of decades of prolonged war: the French-Indochina from 1945 to 1954, then the Vietnam War from 1955 to 1975) as well as the persecution and re-education camps afterward. What my family had to endure created a period of fear and loss into which I was born into in 1976. That year, my family had lost its fortune due to the Communist government seizing of our home and business, plunging us from a comfortable middle- to upper-class life to poverty. There was also widespread fear of systematic rape by the Communist victors. So my family endured great stress and the loss of a way of life leading up to our escape.
For the refugees, the escape itself is often a dangerous journey where, given its emergent nature, they are often exposed to the elements. We know about the current situation in Ukraine and Gaza, where children are fleeing from bombs and bullets. In my situation, we endured weeks of starvation crammed in the hull of boat as we forged through the Indian Ocean to the Philippines. One of my aunts, on a separate trip, perished because her boat had capsized, like so many others. Though impossible to verify, it has been estimated that up to 70% of Vietnamese refugees died during their escape.15 After the boat, my mother and I still had to brave Malaysian jungles and prisons, and then refugee camps for a year before we reached safety at an American Embassy in the Philippines. After we gained sponsorship to America, the traumas did not abate, but were only replaced by those of culture shock, poverty, and alienation. Taken by themselves, significant traumas exist in each phase of a refugee child’s escape, whether before, during, or after. These traumas are likely compounded since they are continuously layered and sustained across years, even decades. They affect not only the children, but their parents, and sometimes even a whole nation of people.
Summary
Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, or social upheavals. It is known that refugees are at greater risk for PTSD and affective and psychotic disorders, presumably due to increased traumatic life events before, during, and after their migration. The writer uses his own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.
Dr. Nguyen is a second year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.
References
1. UNHCR. Global Trends. Forced displacement in 2016. Geneva, Switzerland: The UN Refugee Agency, 2022. https://www.unhcr.org/global-trends.
2. Office of the United Nations High Commissioner for Refugees. The refugee concept under international law. Global compact for safe, orderly and regular migration. https://www.unhcr.org/sites/
3. United Nations. (2023, November 11). The Question of Palestine. Un.org. https://www.un.org/unispal/document/un-general-assembly-renews-unrwa-mandate-press-release/
4. UNICEF. (2023, November 11). Child displacement. Data.unicef.org. https://data.unicef.org/topic/child-migration-and-displacement/displacement
5. Kinzie JD. Immigrants and refugees: The psychiatric perspective. Transcult Psychiatry. 2006 Dec;43(4):577-91. doi: 10.1177/1363461506070782.
6. Eaton W and Harrison G. Ethnic disadvantage and schizophrenia. Acta Psychiatr Scand Suppl. 2000:(407):38-43. doi: 10.1034/j.1600-0447.2000.00007.x.
7. Gilliver SC et al. Recent research on the mental health of immigrants to Sweden: a literature review. Eur J Public Health. 2014 Aug:24 Suppl 1:72-9. doi: 10.1093/eurpub/cku101.
8. Rapp MA et al. When local poverty is more important than your income: Mental health in minorities in inner cities. World Psychiatry. 2015 Jun;14(2):249-50. doi: 10.1002/wps.20221.
9. Cima, Ronald, ed. Vietnam: A Country Study. Washington: GPO for the Library of Congress, 1987.
10. United States Citizenship & Immigration Services (2023, November 12). Refugees. Uscis.gov. https://www.uscis.gov/humanitarian/refugees-and-asylum/refugees
11. Fazel M and Betancourt TS. (2018). Preventive mental health interventions for refugee children and adolescents in high-income settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-32. doi: 10.1016/S2352-4642(17)30147-5.
12. Fazel M et al. Mental health of displaced and refugee children resettled in high-income countries: risk and protective factors. Lancet. 2012 Jan 21;379(9812):266-82. doi: 10.1016/S0140-6736(11)60051-2.
13. Dapunt J et al. Refugees and psychosis: A review of the literature. Transl Psychiatry. 2017 Jun 13;7(6):e1149. doi: 10.1038/tp.2017.119.
14. Fazel M et al. Prevalence of serious mental disorder in 7,000 refugees resettled in western countries: a systematic review. Lancet. 2005 Apr;365(9467):1309-14. doi: 10.1016/S0140-6736(05)61027-6.
15. Rummel R. Statistics of Vietnamese Democide, in his Statistics of Democide. 1997. Table 6.1B,lines 730, 749-51.
Since 1983, when I was a child and fled as a boat refugee from Vietnam with my mother, the international plight of displaced people has only worsened. From 1997 to 2022, the number of forcibly displaced people has more than tripled, growing from 34 million to more than 108 million.1
Displaced people are designated as refugees only when they cross international borders and meet the United Nations High Commissioner for Refugees’ (UNHCR) definition as “persons outside their countries of origin who are in need of international protection because of a serious threat to their life, physical integrity, or freedom in their country of origin as a result of persecution, armed conflict, violence, or serious public disorder.”2 There is a separate mandate by the United Nations for the aid of Palestinian refugees under the United Nations General Assembly’s United Nations Relief and Works Agency for Palestinian Refugees in the Near East (UNRWA).3 Of the displaced in 2022, more than 36 million were recognized as refugees under UNHCR and UNRWA mandates.1 Of these, almost 50% were children, at 17.5 million.4 To make matters worse, worldwide children represent less than one-third of the population.4 Since 2022, the increase in refugeeism is mostly driven by Ukraine and Syria, though also significantly Afghanistan, Venezuela, Sudan, Myanmar, Congo, Somalia, and Central African Republic.4 Refugeeism is a growing problem that disproportionately impacts children through sheer number, and one suspects, given their greater overall vulnerabilities compared with adults, physical and mental health consequences.
Traumas of refugees compared with non-refugee immigrants
In terms of mental health, refugees are distinct from non-refugee immigrants in that they likely experience more severe psychosocial adversities from greater poverty, greater risk of family separation, and uncertainty of the asylum process.5-8
From my own experience, this stems from the urgent nature of the refugee’s displacement, where they are often fleeing an immediate danger. My family had fled persecution from Communist forces and the social economic collapse that rendered Vietnam, for a time, one of the poorest in the world.9 Or, as my mother observed, “We had to leave because even doctors were starving.”
Refugees often have little preparation, have little legal protection since they are often criminalized, and are forced to endure dangerous conditions where they are vulnerable to smugglers and criminals who exploit their unprotected status. Once they arrive in their new country, they often do not have other family as social supports or resources. They themselves become the anchor for future legal and orderly immigration of their remaining family, given that they can extend their refugee status to those left behind.10 These non-refugee immigrants, unlike their refugee counterparts, are often flown to their new homes with more preparation, protecting them from dangerous conditions, and have the benefit of family who provide them with resources. As such, refugees tend to experience more traumatic life events than non-refugee immigrants. This was true in my family where those of us who initially escaped became the anchors to legally, and more safely, immigrate most of our family in Vietnam. We became their resources, likely making their acclimation smoother.
The mental health of refugee children and their caregivers
It is important to understand the stressors affecting the caregivers of children, since effective treatment of their mental health conditions can also benefit the children as well.11 In fact, among the greatest protective factors for refugee children is the presence of an adult caregiver, suggesting that the child’s mental health is dependent on the caregivers.
Those children who are separated show much worse mental health sequalae.12 As such, an understanding of the caregiver’s stressors is important. For example, when we were escaping Vietnam, my mom would protect me from our hardships by talking about our goals in America, minimizing our dangers by saying that we would be rewarded with things like a hamburger with its seemingly impossible amount of meat. Physically, my mother would always sleep with her arms around me and a knife hidden in order to ward off any attackers at night. When I was starving in the hull of a boat, having not eaten for days, my mother begged for food and gave me what she could get. And post-escape, my family focused on work and applied for aid for shelter and food, while encouraging us to invest in education, likely preventing involvement in criminal activities or gangs. Though overall, my family shielded me from the worst consequences, they also passed on their fears. One of my uncles had been killed by the police when he tried to escape, and so my family passed down a deep suspicion of authorities, whether they were the police or school principals. My mother had vivid memories of Communist re-education camps, which likely gave her a lasting fear that a Communist would find out our identities in America and re-capture us.
The mental health risk of refugees
Given that refugees tend to experience greater amounts of traumatic life events and a vast array of stressors sustained across years and even decades before, during, and after migration, it is no wonder they have much higher rates of mental health conditions, most predominantly PTSD and affective disorders.13,14 They are at particular risk of developing psychoses because they are more likely to experience a range of physical, psychological, and psychosocial problems associated with adversities such as violence, discrimination, economic stress, and social isolation.13 For example, the period leading up to my escape consisted of decades of prolonged war: the French-Indochina from 1945 to 1954, then the Vietnam War from 1955 to 1975) as well as the persecution and re-education camps afterward. What my family had to endure created a period of fear and loss into which I was born into in 1976. That year, my family had lost its fortune due to the Communist government seizing of our home and business, plunging us from a comfortable middle- to upper-class life to poverty. There was also widespread fear of systematic rape by the Communist victors. So my family endured great stress and the loss of a way of life leading up to our escape.
For the refugees, the escape itself is often a dangerous journey where, given its emergent nature, they are often exposed to the elements. We know about the current situation in Ukraine and Gaza, where children are fleeing from bombs and bullets. In my situation, we endured weeks of starvation crammed in the hull of boat as we forged through the Indian Ocean to the Philippines. One of my aunts, on a separate trip, perished because her boat had capsized, like so many others. Though impossible to verify, it has been estimated that up to 70% of Vietnamese refugees died during their escape.15 After the boat, my mother and I still had to brave Malaysian jungles and prisons, and then refugee camps for a year before we reached safety at an American Embassy in the Philippines. After we gained sponsorship to America, the traumas did not abate, but were only replaced by those of culture shock, poverty, and alienation. Taken by themselves, significant traumas exist in each phase of a refugee child’s escape, whether before, during, or after. These traumas are likely compounded since they are continuously layered and sustained across years, even decades. They affect not only the children, but their parents, and sometimes even a whole nation of people.
Summary
Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, or social upheavals. It is known that refugees are at greater risk for PTSD and affective and psychotic disorders, presumably due to increased traumatic life events before, during, and after their migration. The writer uses his own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.
Dr. Nguyen is a second year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.
References
1. UNHCR. Global Trends. Forced displacement in 2016. Geneva, Switzerland: The UN Refugee Agency, 2022. https://www.unhcr.org/global-trends.
2. Office of the United Nations High Commissioner for Refugees. The refugee concept under international law. Global compact for safe, orderly and regular migration. https://www.unhcr.org/sites/
3. United Nations. (2023, November 11). The Question of Palestine. Un.org. https://www.un.org/unispal/document/un-general-assembly-renews-unrwa-mandate-press-release/
4. UNICEF. (2023, November 11). Child displacement. Data.unicef.org. https://data.unicef.org/topic/child-migration-and-displacement/displacement
5. Kinzie JD. Immigrants and refugees: The psychiatric perspective. Transcult Psychiatry. 2006 Dec;43(4):577-91. doi: 10.1177/1363461506070782.
6. Eaton W and Harrison G. Ethnic disadvantage and schizophrenia. Acta Psychiatr Scand Suppl. 2000:(407):38-43. doi: 10.1034/j.1600-0447.2000.00007.x.
7. Gilliver SC et al. Recent research on the mental health of immigrants to Sweden: a literature review. Eur J Public Health. 2014 Aug:24 Suppl 1:72-9. doi: 10.1093/eurpub/cku101.
8. Rapp MA et al. When local poverty is more important than your income: Mental health in minorities in inner cities. World Psychiatry. 2015 Jun;14(2):249-50. doi: 10.1002/wps.20221.
9. Cima, Ronald, ed. Vietnam: A Country Study. Washington: GPO for the Library of Congress, 1987.
10. United States Citizenship & Immigration Services (2023, November 12). Refugees. Uscis.gov. https://www.uscis.gov/humanitarian/refugees-and-asylum/refugees
11. Fazel M and Betancourt TS. (2018). Preventive mental health interventions for refugee children and adolescents in high-income settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-32. doi: 10.1016/S2352-4642(17)30147-5.
12. Fazel M et al. Mental health of displaced and refugee children resettled in high-income countries: risk and protective factors. Lancet. 2012 Jan 21;379(9812):266-82. doi: 10.1016/S0140-6736(11)60051-2.
13. Dapunt J et al. Refugees and psychosis: A review of the literature. Transl Psychiatry. 2017 Jun 13;7(6):e1149. doi: 10.1038/tp.2017.119.
14. Fazel M et al. Prevalence of serious mental disorder in 7,000 refugees resettled in western countries: a systematic review. Lancet. 2005 Apr;365(9467):1309-14. doi: 10.1016/S0140-6736(05)61027-6.
15. Rummel R. Statistics of Vietnamese Democide, in his Statistics of Democide. 1997. Table 6.1B,lines 730, 749-51.
Can vitamin and mineral supplementation prevent cancer or cardiovascular disease?
Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.
However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.
Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.
Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.
While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.
What can we do when patients come to us with false claims regarding supplements?
- Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
- Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
- Give the patient resources. Know what websites to direct them to so that they can get accurate information.
- Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
- Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.
Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.
*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.
Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.
However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.
Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.
Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.
While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.
What can we do when patients come to us with false claims regarding supplements?
- Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
- Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
- Give the patient resources. Know what websites to direct them to so that they can get accurate information.
- Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
- Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.
Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.
*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.
Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.
However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.
Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.
Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.
While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.
What can we do when patients come to us with false claims regarding supplements?
- Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
- Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
- Give the patient resources. Know what websites to direct them to so that they can get accurate information.
- Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
- Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.
Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.
*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.
CKD-EPI eGFR formula surpasses alternatives in young adults
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
AT KIDNEY WEEK 2023
A nurse’s view: Women desperately need information about pelvic floor disorders
Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.1
Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
Who is at risk?
To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).
Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.
Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.1 Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.1 Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.
One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.
The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.2 This will greatly impact health care costs.
To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.2 Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.3 Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
What can we do?
The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.1 There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.
At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.
ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.1 Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.
Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.
Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.
The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.4 This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.
There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.
There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.
Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.
References
1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.
2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.
3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.
4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.
Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.1
Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
Who is at risk?
To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).
Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.
Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.1 Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.1 Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.
One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.
The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.2 This will greatly impact health care costs.
To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.2 Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.3 Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
What can we do?
The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.1 There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.
At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.
ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.1 Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.
Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.
Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.
The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.4 This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.
There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.
There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.
Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.
References
1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.
2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.
3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.
4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.
Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.1
Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
Who is at risk?
To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).
Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.
Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.1 Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.1 Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.
One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.
The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.2 This will greatly impact health care costs.
To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.2 Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.3 Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
What can we do?
The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.1 There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.
At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.
ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.1 Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.
Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.
Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.
The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.4 This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.
There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.
There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.
Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.
References
1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.
2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.
3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.
4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.
The easy way to talk about penises
This transcript has been edited for clarity.
I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.
The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.
It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?
Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.
I tell them it’s a 4-number scale. A “1” is no erection at all. A “2” is when it gets harder and larger, but it’s not going to penetrate. A “3” will penetrate, but it’s pretty wobbly. A “4” is that perfect cucumber–porn star erection that everyone is seeking. I have the patient tell me a story. They may say, “When I wake up in the morning, I’m at a 2. When I stimulate myself, I can get up to a 3. When I’m with my partner, sometimes I can get up to a 4.”
This is really helpful because they can talk in numbers. And after I give them treatments such as lifestyle changes, sex therapy, testosterone, a PDE5 inhibitor such as Viagra or Cialis, or an injection, they can come back and tell me how the story has changed. I have an objective measure that shows me how the treatment is affecting their erections. Not only do I feel more confident having those objective measures, but my patients feel more confident in the care that they’re getting, and they feel more comfortable talking to me about the changes. So, I encourage all of you to bring that EHS tool into your office. Show it to patients and get them more comfortable talking about erections.
Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.
The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.
It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?
Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.
I tell them it’s a 4-number scale. A “1” is no erection at all. A “2” is when it gets harder and larger, but it’s not going to penetrate. A “3” will penetrate, but it’s pretty wobbly. A “4” is that perfect cucumber–porn star erection that everyone is seeking. I have the patient tell me a story. They may say, “When I wake up in the morning, I’m at a 2. When I stimulate myself, I can get up to a 3. When I’m with my partner, sometimes I can get up to a 4.”
This is really helpful because they can talk in numbers. And after I give them treatments such as lifestyle changes, sex therapy, testosterone, a PDE5 inhibitor such as Viagra or Cialis, or an injection, they can come back and tell me how the story has changed. I have an objective measure that shows me how the treatment is affecting their erections. Not only do I feel more confident having those objective measures, but my patients feel more confident in the care that they’re getting, and they feel more comfortable talking to me about the changes. So, I encourage all of you to bring that EHS tool into your office. Show it to patients and get them more comfortable talking about erections.
Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.
The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.
It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?
Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.
I tell them it’s a 4-number scale. A “1” is no erection at all. A “2” is when it gets harder and larger, but it’s not going to penetrate. A “3” will penetrate, but it’s pretty wobbly. A “4” is that perfect cucumber–porn star erection that everyone is seeking. I have the patient tell me a story. They may say, “When I wake up in the morning, I’m at a 2. When I stimulate myself, I can get up to a 3. When I’m with my partner, sometimes I can get up to a 4.”
This is really helpful because they can talk in numbers. And after I give them treatments such as lifestyle changes, sex therapy, testosterone, a PDE5 inhibitor such as Viagra or Cialis, or an injection, they can come back and tell me how the story has changed. I have an objective measure that shows me how the treatment is affecting their erections. Not only do I feel more confident having those objective measures, but my patients feel more confident in the care that they’re getting, and they feel more comfortable talking to me about the changes. So, I encourage all of you to bring that EHS tool into your office. Show it to patients and get them more comfortable talking about erections.
Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.
A version of this article appeared on Medscape.com.
Renewing the dream
The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”1 One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.2
Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).3 Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.6 We launched the venture, got organized, made it. We are an institution.
The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.3 The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.3
In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.7 The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.
While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.8-11 These organizations are aligning around re-centering on patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.12 We are indeed dreaming a new dream.
While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.
The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.
1. Fox TF. The personal doctor and his relation to the hospital. Observations and reflections on some American experiments in general practice by groups. Lancet. 1960;2:743-760.
2. Stephens, GG. The Intellectual Basis of Family Practice. Winter Publishing and Society of Teachers of Family Medicine; 1982.
3. Bridges W, Bridges S. Managing Transitions: Making the Most of Change. 4th ed. Da Capo Press; 2016.
4. Association of American Medical Colleges. Physician specialty data report. Accessed October 25, 2023. www.aamc.org/data-reports/workforce/data/active-physicians-us-doctor-medicine-us-md-degree-specialty-2019
5. American Academy of Family Physicians. 2023 match results for family medicine. Accessed October 25, 2023. www.aafp.org/students-residents/residency-program-directors/national-resident-matching-program-results.html
6. Robert Graham Center. Primary Care in the US: A Chartbook of Facts and Statistics. Accessed October 25, 2023. www.graham-center.org/content/dam/rgc/documents/publications-reports/reports/PrimaryCareChartbook2021.pdf
7. Ministry of Health Singapore. What is Healthier SG? Accessed October 25, 2023. www.healthiersg.gov.sg/about/what-is-healthier-sg/
8. The Robert Graham Center. Accessed October 25, 2023. www.graham-center.org/home.html
9. Stange KC. Holding on and letting go: a perspective from the Keystone IV Conference. J Am Board Fam Med. 2016;29:S32-S39.
10. American Board of Family Medicine. Family medicine certification. Accessed October 25, 2023. www.theabfm.org/research-articles/family-medicine-certification?page=1
11. National Academies of Sciences, Engineering, and Medicine. Implementing high-quality primary care. Accessed October 25, 2023. www.nationalacademies.org/our-work/implementing-high-quality-primary-care
12. Sinsky CA, Panzer J. The solution shop and the production line—the case for a frameshift for physician practices. N Engl J Med. 2022;386:2452-2453.
Editor-in-Chief
[email protected]
Editor-in-Chief
[email protected]
Editor-in-Chief
[email protected]
The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”1 One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.2
Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).3 Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.6 We launched the venture, got organized, made it. We are an institution.
The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.3 The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.3
In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.7 The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.
While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.8-11 These organizations are aligning around re-centering on patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.12 We are indeed dreaming a new dream.
While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.
The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.
The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”1 One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.2
Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).3 Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.6 We launched the venture, got organized, made it. We are an institution.
The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.3 The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.3
In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.7 The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.
While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.8-11 These organizations are aligning around re-centering on patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.12 We are indeed dreaming a new dream.
While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.
The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.
1. Fox TF. The personal doctor and his relation to the hospital. Observations and reflections on some American experiments in general practice by groups. Lancet. 1960;2:743-760.
2. Stephens, GG. The Intellectual Basis of Family Practice. Winter Publishing and Society of Teachers of Family Medicine; 1982.
3. Bridges W, Bridges S. Managing Transitions: Making the Most of Change. 4th ed. Da Capo Press; 2016.
4. Association of American Medical Colleges. Physician specialty data report. Accessed October 25, 2023. www.aamc.org/data-reports/workforce/data/active-physicians-us-doctor-medicine-us-md-degree-specialty-2019
5. American Academy of Family Physicians. 2023 match results for family medicine. Accessed October 25, 2023. www.aafp.org/students-residents/residency-program-directors/national-resident-matching-program-results.html
6. Robert Graham Center. Primary Care in the US: A Chartbook of Facts and Statistics. Accessed October 25, 2023. www.graham-center.org/content/dam/rgc/documents/publications-reports/reports/PrimaryCareChartbook2021.pdf
7. Ministry of Health Singapore. What is Healthier SG? Accessed October 25, 2023. www.healthiersg.gov.sg/about/what-is-healthier-sg/
8. The Robert Graham Center. Accessed October 25, 2023. www.graham-center.org/home.html
9. Stange KC. Holding on and letting go: a perspective from the Keystone IV Conference. J Am Board Fam Med. 2016;29:S32-S39.
10. American Board of Family Medicine. Family medicine certification. Accessed October 25, 2023. www.theabfm.org/research-articles/family-medicine-certification?page=1
11. National Academies of Sciences, Engineering, and Medicine. Implementing high-quality primary care. Accessed October 25, 2023. www.nationalacademies.org/our-work/implementing-high-quality-primary-care
12. Sinsky CA, Panzer J. The solution shop and the production line—the case for a frameshift for physician practices. N Engl J Med. 2022;386:2452-2453.
1. Fox TF. The personal doctor and his relation to the hospital. Observations and reflections on some American experiments in general practice by groups. Lancet. 1960;2:743-760.
2. Stephens, GG. The Intellectual Basis of Family Practice. Winter Publishing and Society of Teachers of Family Medicine; 1982.
3. Bridges W, Bridges S. Managing Transitions: Making the Most of Change. 4th ed. Da Capo Press; 2016.
4. Association of American Medical Colleges. Physician specialty data report. Accessed October 25, 2023. www.aamc.org/data-reports/workforce/data/active-physicians-us-doctor-medicine-us-md-degree-specialty-2019
5. American Academy of Family Physicians. 2023 match results for family medicine. Accessed October 25, 2023. www.aafp.org/students-residents/residency-program-directors/national-resident-matching-program-results.html
6. Robert Graham Center. Primary Care in the US: A Chartbook of Facts and Statistics. Accessed October 25, 2023. www.graham-center.org/content/dam/rgc/documents/publications-reports/reports/PrimaryCareChartbook2021.pdf
7. Ministry of Health Singapore. What is Healthier SG? Accessed October 25, 2023. www.healthiersg.gov.sg/about/what-is-healthier-sg/
8. The Robert Graham Center. Accessed October 25, 2023. www.graham-center.org/home.html
9. Stange KC. Holding on and letting go: a perspective from the Keystone IV Conference. J Am Board Fam Med. 2016;29:S32-S39.
10. American Board of Family Medicine. Family medicine certification. Accessed October 25, 2023. www.theabfm.org/research-articles/family-medicine-certification?page=1
11. National Academies of Sciences, Engineering, and Medicine. Implementing high-quality primary care. Accessed October 25, 2023. www.nationalacademies.org/our-work/implementing-high-quality-primary-care
12. Sinsky CA, Panzer J. The solution shop and the production line—the case for a frameshift for physician practices. N Engl J Med. 2022;386:2452-2453.
The steep costs of disrupting gut-barrier harmony
An interview with Elena Ivanina, DO, MPH
From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.
To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.
What is the role of the gut barrier in overall health and disease?
The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.
The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.
Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.
Is disruption of this barrier what is usually referred to as “leaky gut”?
Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.
Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?
Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.
In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.
In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
The many possible sources of gut-barrier disruption
What causes leaky gut, and when should physicians and patients be suspicious if they have it?
There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO2 max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.
Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.
What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?
The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.
With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.
A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
Emerging evidence on causality
New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?
Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.
Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.
In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.
In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.
These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.
What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?
There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.
Is there an association between alterations in the gut microbiome and gut-barrier disruption?
There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.
The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.
Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
Practical advice for clinicians and patients
How do you advise patients to avoid gut-barrier disruption?
It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.
Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?
Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.
Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.
What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?
It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.
A version of this article appeared on Medscape.com.
An interview with Elena Ivanina, DO, MPH
An interview with Elena Ivanina, DO, MPH
From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.
To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.
What is the role of the gut barrier in overall health and disease?
The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.
The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.
Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.
Is disruption of this barrier what is usually referred to as “leaky gut”?
Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.
Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?
Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.
In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.
In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
The many possible sources of gut-barrier disruption
What causes leaky gut, and when should physicians and patients be suspicious if they have it?
There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO2 max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.
Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.
What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?
The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.
With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.
A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
Emerging evidence on causality
New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?
Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.
Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.
In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.
In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.
These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.
What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?
There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.
Is there an association between alterations in the gut microbiome and gut-barrier disruption?
There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.
The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.
Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
Practical advice for clinicians and patients
How do you advise patients to avoid gut-barrier disruption?
It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.
Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?
Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.
Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.
What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?
It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.
A version of this article appeared on Medscape.com.
From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.
To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.
What is the role of the gut barrier in overall health and disease?
The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.
The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.
Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.
Is disruption of this barrier what is usually referred to as “leaky gut”?
Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.
Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?
Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.
In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.
In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
The many possible sources of gut-barrier disruption
What causes leaky gut, and when should physicians and patients be suspicious if they have it?
There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO2 max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.
Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.
What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?
The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.
With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.
A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
Emerging evidence on causality
New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?
Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.
Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.
In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.
In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.
These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.
What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?
There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.
Is there an association between alterations in the gut microbiome and gut-barrier disruption?
There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.
The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.
Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
Practical advice for clinicians and patients
How do you advise patients to avoid gut-barrier disruption?
It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.
Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?
Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.
Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.
What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?
It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.
A version of this article appeared on Medscape.com.