Feature

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

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

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

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

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

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

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

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

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

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

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

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

Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.

This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
 

Treat appropriately for pain

Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.

“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”

Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”

Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.

“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
 

Practice lifestyle and preventive medicine

Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.

“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.

Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.

“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.

Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
 

Patient care is at the core of medicine

Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.

“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”

But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.

“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”

Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.

“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
 

Physician, heal thyself

Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”

Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
 

Practice with gender at the forefront

Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.

“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”

Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.

“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.

“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
 

Talk about racial disparities

John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.

“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”

Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.

“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
 

Information at your fingertips

For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.

“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”

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

Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.

This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
 

Treat appropriately for pain

Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.

“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”

Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”

Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.

“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
 

Practice lifestyle and preventive medicine

Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.

“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.

Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.

“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.

Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
 

Patient care is at the core of medicine

Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.

“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”

But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.

“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”

Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.

“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
 

Physician, heal thyself

Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”

Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
 

Practice with gender at the forefront

Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.

“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”

Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.

“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.

“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
 

Talk about racial disparities

John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.

“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”

Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.

“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
 

Information at your fingertips

For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.

“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”

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

Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.

This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
 

Treat appropriately for pain

Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.

“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”

Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”

Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.

“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
 

Practice lifestyle and preventive medicine

Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.

“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.

Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.

“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.

Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
 

Patient care is at the core of medicine

Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.

“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”

But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.

“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”

Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.

“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
 

Physician, heal thyself

Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”

Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
 

Practice with gender at the forefront

Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.

“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”

Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.

“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.

“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
 

Talk about racial disparities

John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.

“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”

Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.

“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
 

Information at your fingertips

For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.

“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

One of the most controversial issues today is whether a physician should be permitted, or even obligated, to assist patients with a terminal or incurable illness to end their life – a process known as medical assistance in dying (MAID) or physician-assisted suicide (PAS.)

Until recently, this contentious issue applied only to patients with physical illnesses who want to end their suffering and who seek out a physician willing to assist with that objective. In the United States and other countries, this is the patient population who may be able to avail themselves of this option.

However, newly proposed legislation in Canada – which has the largest number of physician-assisted deaths worldwide – would expand the indication for MAID to include serious mental illness. Originally set to be passed in March 2023, the law has been deferred for final decision until March 2024.

A recent commentary by psychiatrist Dinah Miller, MD, explored the ethics of this proposed legislation for mental health professionals. “To offer the option of death facilitated by the very person who is trying to get [patients with serious mental illness] better seems so counter to everything I have learned and contradicts our role as psychiatrists who work so hard to prevent suicide,” Dr. Miller wrote. “As psychiatrists, do we offer hope to our most vulnerable patients, or do we offer death? Do we rail against suicide, or do we facilitate it?”

Dr. Miller’s piece garnered a huge amount of reader response that included many laudatory comments: a “nuanced and open-ended inquiry here,” “timely and honest,” and “beautifully written.” One reader thanked the author for “this thoughtful, questioning, and open reflection on what it means to be a psychiatrist facing a thorny and deeply personal practice and philosophical question.”
 

Cognitive distortion or objective reality?

Many readers were opposed to any type of physician involvement in hastening a patient’s death, regardless of whether the condition is medical or psychiatric. “Let others who wish to die make their own arrangement without the aid of the medical profession,” one reader wrote.

But others felt that for those with terminal physical illnesses or intractable pain, it is justified for medical professionals to either facilitate death or, at the very least, withhold life-prolonging treatments.

A critical-care physician described responding to families’ accusations that withdrawal of life-sustaining measures means “playing God.” On the contrary, the physician wrote, “there is a limit to our abilities; and withdrawing those life-prolonging interventions allows nature or God or whatever to play a role and take its course.”

Another U.S. reader pointed out that “multiple polls in this country have shown that the majority of the general public, physicians in general and psychiatrists in particular, support the option of MAID for the terminally ill. They do not find it at variance with their calling as physicians.”

“I and many of my elderly friends don’t fear death but fear prolonged dementia with its dependency and lack of quality of life,” one reader wrote. “We would be much more at peace if we could put in our advanced directive that we request MAID once some point of dependency has been reached.”

Another wrote that in the event of entering a state of “degrading dependency and hardship on the family, please let me go peacefully, without burdening others, into that good night [of death].”

Many felt that not only physical illness but also the prospect of cognitive degeneration – specifically dementia – also justifies assisting patient death.
 

“Enormous suffering”

One Canadian reader noted that provisions for advance consent are now in place in Canada for those facing the prospect of neurodegenerative disease and who are still mentally competent to make such decisions.

But therein lies the rub – the concept of an advanced directive goes to the question of decisional capacity. Dr. Miller noted that “depression distorts cognition and leads many patients to believe that they would be better off dead and that their loves ones would be better off without them.”

The concept of “cognitive distortion” implies that the illness itself may impede the decisional capacity required for an advanced directive or a decision made in the moment, in the absence of such a directive. Dr. Miller asked, “How do we determine whether patients with serious mental illness are competent to make such a decision or whether it is mental illness that is driving their perception of a future without hope?”

One reader attested to this from personal experience. “As both a physician and a sufferer of severe, often profound depression for 50 years, I can confidently say that ... the pursuit of death is the result of an impaired mental state, which simultaneously prevents a rational decision.”

Another agreed. “As a psychiatrist, I treated suicidal patients almost every day of my 27-year career. I believe in making every effort to prevent the suicide of a healthy depressed person and I do not support MAID for psychiatric conditions. But I do support MAID for the terminally ill.”

Other readers disagreed. In the words of one commentator, “I think that if we are going to help mentally ill people, we have to consider their choices. The stress imposed by a severe/intractable mental illness is as bad as any other devastating medical illness. If no one is going to hold their hand in life (as support services are limited and psychiatric treatments often fail), allow a medical professional to hold their hand through their final moments.”

A psychiatrist described very ill patients with treatment-resistant bipolar disorder who had not only received medications, including ketamine, but had also received electroconvulsive therapy and still did not respond.

“Their suffering is enormous and the truth is that there is no improvement for more than a few days or weeks and later they return to their hell. Appreciating that they would be better off dead for themselves and their families is not always a cognitive distortion but an objective evaluation of their reality.”

However, as another reader pointed out, an issue with the argument presented here is that it presupposes that MAID requires “clinical justification.” But in Canada, “MAID ... is understood as an expression of personal autonomy. Rooted in liberal political philosophy of individualism ... approval for death need not be based on a clinical assessment.” Instead, “death is seen as a ‘right’ that the state must therefore provide.”
 

Another form of eugenics?

Dr. Miller raised the ethical implications of racial and socioeconomic factors playing a role in the consideration of MAID for those with psychiatric illness.

“Might those who are poor, who have less access to expensive treatment options and social support, be more likely to request facilitated death?” she asks. “Do we risk facilitating a patient’s demise when other options are unavailable because of a lack of access to treatment or when social and financial struggles exacerbate a person’s hopelessness? Should we worry that psychiatric euthanasia will turn into a form of eugenics where those who can’t contribute are made to feel that they should bow out?”

Several readers agreed. “Looking at the disproportionate burden of illness, rates of imprisonment, and application of the death penalty indicates to me that race and socioeconomic status will be an immediate factor in how, where, and with whom MAID for mental illness would be practice in much, if not all, of the U.S.,” wrote one physician.

A Canadian reader expressed similar concerns. “I’ve seen a handful of people, including someone I considered a good friend, opt for MAID because it was easier than living as a disabled person in poverty without adequate mental health care.”

Another Canadian clinician noted that offering people good care can make all the difference. “As a Canadian mental health clinician who served youth with severe mental illness for over 20 years through our socialized medical network, I can attest to the difference good care usually makes in shifting clients from despair and a commitment to death to embracing life once again. Let’s not, as clinicians, embrace easing a government/state-sanctioned pathway to death.”

Some readers believe that these types of issues can’t be solved with a blanket approach, noting that each case is different. “Real life is always more complicated than academic discussions. Having served on a hospital ethics committee, I know that each case is unique,” one reader noted.

Another reader added, “I think all we can do as physicians is to let people decide for themselves and participate only if our conscience allows.”
 

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

The utility of artificial intelligence in pulmonology has focused mainly on using image datasets to detect and diagnose lung malignancies, but now a growing number of AI models are emerging that apply machine learning to improve predictability for other pulmonary conditions, including pulmonary infections, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD).

These applications are moving beyond the traditional AI model of collecting data from a multitude of images to cast a wider data net that includes electronic health records.

Also on the horizon, ChatGPT technology is poised to have an impact. But pulmonologists and their practices have a number of barriers to clear before they feel a meaningful impact from AI.

The imperative, said AI researcher Ishanu Chattopadhyay, PhD, is to create transformative models that can detect lung disease early on. Dr. Chattopadhyay, an assistant professor of medicine at the University of Chicago and its Institute for Genomics and Systems Biology, and fellow researchers developed an AI algorithm that uses comorbidity signatures in electronic health records to screen for idiopathic pulmonary fibrosis (IPF) (Nature Med. 2022 Sep 29. doi: 10.1038/s41591-022-02010-y).

“If you could do this when somebody walks into a primary care setting and they are barely suspecting something is going on with them or when they don’t have the typical risk factors, there is a certain fraction of these people who do have IPF and they will almost invariably be diagnosed late and/or misdiagnosed,” Dr. Chattopadhyay said, citing a study that found 55% of patients with IPF have had at least one misdiagnosis and 38% have two or more misdiagnoses (BMC Pulm Med. 2018 Jan 17. doi: 10.1186/s12890-017-0560-x).

Harnessing massive data sets

AI models cull data sets, whether banks of radiographic images or files in an EHR, to extract telltale signatures of a disease state. Dr. Chattopadhyay and his team’s model used three databases with almost 3 million participants and 54,247 positive cases of IPF. Hospitals in Scotland have deployed what they’ve claimed are the first AI models to predict COPD built with 55,000 patient records from a regional National Health Service database. Another AI model for staging COPD, developed by researchers in the United States and Romania, used more than 18,000 medical records from 588 patients to identify physiological signals predictive of COPD (Advanced Sci. 2023 Feb 19. doi: 10.1002/advs.202203485).

Said Dr. Chattopadhyay: “If I can bring in AI which doesn’t just look at radiological images but actually gets it back where someone walks into primary care using only the information that is available at that point in the patient files and asking for nothing more, it raises a flag reliably that gets you a pulmonary referral that will hopefully reduce the misdiagnosis and late diagnosis.”

Victor Tseng, MD, medical director for pulmonology at Ansible Health in Mountain View, Calif., who’s researching the potential of AI in pulmonology, speculated on what functions AI can perform in the clinic. “I think you will start to see much more interventional sort of clinically patient care–facing applications,” he said. That would include acting as a triage layer to direct patient queries to a nurse, physician, or another practitioner, providing patient instructions, serving as therapeutic software, coordinating care, integrating supply chain issues,” he said.

 

AI vs. spirometry for COPD

Researchers in the United States and Romania, led by Paul Bogdan, PhD, at the University of Southern California Viterbi School of Engineering, developed a model that predicted COPD with an accuracy of almost 99% (98.66%) and avoids many of the shortcomings of spirometry, Dr. Bogdan said.

USC Viterbi School of Engineering

The models developed by Dr. Bogdan and collaborators use a different principle than existing AI platforms, Dr. Bogdan said. They analyze the properties of the data. As he explained it, they exploit what he called the “geometry of these data” to make inferences and decisions on a patient’s risk for COPD.

“Deep learning is very good for images, for videos, but it doesn’t work that well for signals,” said Mihai Udrescu, PhD, one of the Romanian collaborators. “But if we process the data with the technique brought up by Paul [Bogdan] and his team at USC, deep learning also works well on physiological signals.”

Dr. Paul Bogdan

Said Dr. Bogdan, “Nobody thought about using physiological signals to predict COPD before this work. They used spirometry, but spirometry is cumbersome and several steps have to be performed in order to have an accurate spirometry.” His team’s AI models extract and analyze risk data based on 10 minutes of monitoring.

This technology also has the potential to improve accessibility of COPD screening, Dr. Udrescu said. “It can democratize the access to the health care because you don’t need to travel for 100 or 200 miles to see a specialist,” he said. “You just send an app to the mobile phone of a patient, the person puts on a smart watch and wears it for a couple of minutes and the data is either recorded locally or is transmitted and it is analyzed.” The computations can be done locally and in a matter of minutes, he said.

In Scotland, a 12-month feasibility study is underway to evaluate an AI model to identify COPD patients at greatest risk for adverse events. A press release from Lenus, the company developing the technology, said the study will use a COPD multidisciplinary team to consider real-time AI model outputs to enable proactive patient encounters and reduce emergency care visits.

Researchers in Paris built an AI model that showed a 68% accuracy in distinguishing people with asthma from people with COPD in administrative medical databases (BMC Pulmon Med. 2022 Sep 20. doi: 10.1186/s12890-022-02144-2). They found that asthma patients were younger than those with COPD (a mean of 49.9 vs. 72.1 years) and that COPD occurred mostly in men (68% vs. 33%). And an international team of researchers reported that an AI model that used chest CT scans determined that ever-smokers with COPD who met the imaging criteria for bronchiectasis were more prone to disease exacerbations (Radiology. 2022 Dec 13. doi: 10.1148/radiol.221109). 

 

AI in idiopathic pulmonary fibrosis

The AI model that Dr. Chattopadhyay and collaborators developed had an 88% accuracy in predicting IPF. The model, known as the zero-burden comorbidity risk score for IPF (ZCoR-IPF), identified IPF cases in adults age 45 and older 1-4 years sooner than in a variety of pulmonology practice settings.

The model accounted for about 700 different features of IPF, Dr. Chattopadhyay said, but it deviated from standard AI risk models in that it used a machine learning algorithm to extract disease features that aren’t well understood or even known. “We do not know what all the risk factors of IPF are,” he said. “People who don’t have all the risk factors still get IPF. So we have to step back from the raw EHR data from where the features are being generated automatically, and then you can apply standard ML tools.”

Researchers at Nagoya University in Japan also reported on an AI algorithm for predicting IPF that used 646,800 high-resolution CT images and medical records data from 1,068 patients. Their algorithm had an average diagnostic accuracy of 83.6% and, they reported, demonstrated good accuracy even in patients with signs of interstitial pneumonia or who had surgical lung biopsies (Respirology. 2022 Dec 13. doi: 10.1111/resp.14310).

 

Chat GPT: The next frontier in AI

Dr. Tseng last year led a group of researchers that fed questions from the United States Medical Licensing Exam to a ChatGPT model, which found it answered 60%-65% of questions correctly (PLOS Digit Health. 2023 Feb 9. doi: 10.1371/journal.pdig.0000198). As Dr. Tseng pointed out, that’s good enough to get a medical license.

It may be a matter of time before ChatGPT technology finds its way into the clinic, Dr. Tseng said. A quick ChatGPT query of how it could be used in medicine yielded 12 different answers, from patient triage to providing basic first aid instructions in an emergency.

Dr. Tseng, who’s pulmonology practice places an emphasis on virtual care delivery, went deeper than the ChatGPT answer. “If you’re a respiratory therapist and you’re trying to execute a complicated medical care plan written by a physician, there’s a natural disconnect between our language and their language,” he said. “What we have found is that GPT has significantly harmonized the care plan. And that’s amazing because you end up with this single-stream understanding of the care plan, where the language is halfway between a bedside clinician, like the respiratory therapist or nurse, and is also something that a physician can understand and take the bigger sort of direction of care from.”

 

Barriers to AI in clinic

Numerous barriers face widespread adoption of AI tools in the clinic, Dr. Tseng said, including physician and staff anxiety about learning new technology. “AI tools, for all purposes, are supposed to allay the cognitive burden and the tedium burden on clinicians, but end up actually costing more time,” he said.

Health care organizations will also need to retool for AI, a group of medical informatics and digital health experts, led by Laurie Lovett Novak, PhD, reported (JAMIA Open. 2023 May 3. doi: 10.1093/jamiaopen/ooad028). But it’s coming nonetheless, Dr. Novak, an associate professor of biomedical informatics at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview.

“In the near future, managers in clinics and inpatient units will be overseeing care that involves numerous AI-based technologies, including predictive analytics, imaging tools, language models, and others,” she said. “Organizations need to support managers by implementing capabilities for algorithmo-vigilance.”

That would include dealing with what she called “algorithmic drift” – when the accuracy of an AI model wanes because of changes in the underlying data – and ensuring that models are unbiased and aren’t used in a way that contributes to inequities in health care. “These new organizational capabilities will demand new tools and new competencies,” she said. That would include policies and processes drawing guidance from medical societies for legal and regulatory direction for managers, staff training, and software documentation.

Dr. Tseng envisioned how AI would work in the clinic. “I personally think that, at some time in the near future, AI-driven care coordination, where the AI basically handles appointment scheduling, patient motivation, patient engagement and acts as their health navigator, will be superior to any human health navigator on the whole, only for the reason that AI is indefatigable,” Dr. Tseng said. “It doesn’t get tired, it doesn’t get burned out, and these health navigation care coordination roles are notoriously difficult.”

The physicians and researchers interviewed for this report had no relevant relationships to disclose.

The utility of artificial intelligence in pulmonology has focused mainly on using image datasets to detect and diagnose lung malignancies, but now a growing number of AI models are emerging that apply machine learning to improve predictability for other pulmonary conditions, including pulmonary infections, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD).

These applications are moving beyond the traditional AI model of collecting data from a multitude of images to cast a wider data net that includes electronic health records.

Also on the horizon, ChatGPT technology is poised to have an impact. But pulmonologists and their practices have a number of barriers to clear before they feel a meaningful impact from AI.

The imperative, said AI researcher Ishanu Chattopadhyay, PhD, is to create transformative models that can detect lung disease early on. Dr. Chattopadhyay, an assistant professor of medicine at the University of Chicago and its Institute for Genomics and Systems Biology, and fellow researchers developed an AI algorithm that uses comorbidity signatures in electronic health records to screen for idiopathic pulmonary fibrosis (IPF) (Nature Med. 2022 Sep 29. doi: 10.1038/s41591-022-02010-y).

“If you could do this when somebody walks into a primary care setting and they are barely suspecting something is going on with them or when they don’t have the typical risk factors, there is a certain fraction of these people who do have IPF and they will almost invariably be diagnosed late and/or misdiagnosed,” Dr. Chattopadhyay said, citing a study that found 55% of patients with IPF have had at least one misdiagnosis and 38% have two or more misdiagnoses (BMC Pulm Med. 2018 Jan 17. doi: 10.1186/s12890-017-0560-x).

Harnessing massive data sets

AI models cull data sets, whether banks of radiographic images or files in an EHR, to extract telltale signatures of a disease state. Dr. Chattopadhyay and his team’s model used three databases with almost 3 million participants and 54,247 positive cases of IPF. Hospitals in Scotland have deployed what they’ve claimed are the first AI models to predict COPD built with 55,000 patient records from a regional National Health Service database. Another AI model for staging COPD, developed by researchers in the United States and Romania, used more than 18,000 medical records from 588 patients to identify physiological signals predictive of COPD (Advanced Sci. 2023 Feb 19. doi: 10.1002/advs.202203485).

Said Dr. Chattopadhyay: “If I can bring in AI which doesn’t just look at radiological images but actually gets it back where someone walks into primary care using only the information that is available at that point in the patient files and asking for nothing more, it raises a flag reliably that gets you a pulmonary referral that will hopefully reduce the misdiagnosis and late diagnosis.”

Victor Tseng, MD, medical director for pulmonology at Ansible Health in Mountain View, Calif., who’s researching the potential of AI in pulmonology, speculated on what functions AI can perform in the clinic. “I think you will start to see much more interventional sort of clinically patient care–facing applications,” he said. That would include acting as a triage layer to direct patient queries to a nurse, physician, or another practitioner, providing patient instructions, serving as therapeutic software, coordinating care, integrating supply chain issues,” he said.

 

AI vs. spirometry for COPD

Researchers in the United States and Romania, led by Paul Bogdan, PhD, at the University of Southern California Viterbi School of Engineering, developed a model that predicted COPD with an accuracy of almost 99% (98.66%) and avoids many of the shortcomings of spirometry, Dr. Bogdan said.

USC Viterbi School of Engineering

The models developed by Dr. Bogdan and collaborators use a different principle than existing AI platforms, Dr. Bogdan said. They analyze the properties of the data. As he explained it, they exploit what he called the “geometry of these data” to make inferences and decisions on a patient’s risk for COPD.

“Deep learning is very good for images, for videos, but it doesn’t work that well for signals,” said Mihai Udrescu, PhD, one of the Romanian collaborators. “But if we process the data with the technique brought up by Paul [Bogdan] and his team at USC, deep learning also works well on physiological signals.”

Dr. Paul Bogdan

Said Dr. Bogdan, “Nobody thought about using physiological signals to predict COPD before this work. They used spirometry, but spirometry is cumbersome and several steps have to be performed in order to have an accurate spirometry.” His team’s AI models extract and analyze risk data based on 10 minutes of monitoring.

This technology also has the potential to improve accessibility of COPD screening, Dr. Udrescu said. “It can democratize the access to the health care because you don’t need to travel for 100 or 200 miles to see a specialist,” he said. “You just send an app to the mobile phone of a patient, the person puts on a smart watch and wears it for a couple of minutes and the data is either recorded locally or is transmitted and it is analyzed.” The computations can be done locally and in a matter of minutes, he said.

In Scotland, a 12-month feasibility study is underway to evaluate an AI model to identify COPD patients at greatest risk for adverse events. A press release from Lenus, the company developing the technology, said the study will use a COPD multidisciplinary team to consider real-time AI model outputs to enable proactive patient encounters and reduce emergency care visits.

Researchers in Paris built an AI model that showed a 68% accuracy in distinguishing people with asthma from people with COPD in administrative medical databases (BMC Pulmon Med. 2022 Sep 20. doi: 10.1186/s12890-022-02144-2). They found that asthma patients were younger than those with COPD (a mean of 49.9 vs. 72.1 years) and that COPD occurred mostly in men (68% vs. 33%). And an international team of researchers reported that an AI model that used chest CT scans determined that ever-smokers with COPD who met the imaging criteria for bronchiectasis were more prone to disease exacerbations (Radiology. 2022 Dec 13. doi: 10.1148/radiol.221109). 

 

AI in idiopathic pulmonary fibrosis

The AI model that Dr. Chattopadhyay and collaborators developed had an 88% accuracy in predicting IPF. The model, known as the zero-burden comorbidity risk score for IPF (ZCoR-IPF), identified IPF cases in adults age 45 and older 1-4 years sooner than in a variety of pulmonology practice settings.

The model accounted for about 700 different features of IPF, Dr. Chattopadhyay said, but it deviated from standard AI risk models in that it used a machine learning algorithm to extract disease features that aren’t well understood or even known. “We do not know what all the risk factors of IPF are,” he said. “People who don’t have all the risk factors still get IPF. So we have to step back from the raw EHR data from where the features are being generated automatically, and then you can apply standard ML tools.”

Researchers at Nagoya University in Japan also reported on an AI algorithm for predicting IPF that used 646,800 high-resolution CT images and medical records data from 1,068 patients. Their algorithm had an average diagnostic accuracy of 83.6% and, they reported, demonstrated good accuracy even in patients with signs of interstitial pneumonia or who had surgical lung biopsies (Respirology. 2022 Dec 13. doi: 10.1111/resp.14310).

 

Chat GPT: The next frontier in AI

Dr. Tseng last year led a group of researchers that fed questions from the United States Medical Licensing Exam to a ChatGPT model, which found it answered 60%-65% of questions correctly (PLOS Digit Health. 2023 Feb 9. doi: 10.1371/journal.pdig.0000198). As Dr. Tseng pointed out, that’s good enough to get a medical license.

It may be a matter of time before ChatGPT technology finds its way into the clinic, Dr. Tseng said. A quick ChatGPT query of how it could be used in medicine yielded 12 different answers, from patient triage to providing basic first aid instructions in an emergency.

Dr. Tseng, who’s pulmonology practice places an emphasis on virtual care delivery, went deeper than the ChatGPT answer. “If you’re a respiratory therapist and you’re trying to execute a complicated medical care plan written by a physician, there’s a natural disconnect between our language and their language,” he said. “What we have found is that GPT has significantly harmonized the care plan. And that’s amazing because you end up with this single-stream understanding of the care plan, where the language is halfway between a bedside clinician, like the respiratory therapist or nurse, and is also something that a physician can understand and take the bigger sort of direction of care from.”

 

Barriers to AI in clinic

Numerous barriers face widespread adoption of AI tools in the clinic, Dr. Tseng said, including physician and staff anxiety about learning new technology. “AI tools, for all purposes, are supposed to allay the cognitive burden and the tedium burden on clinicians, but end up actually costing more time,” he said.

Health care organizations will also need to retool for AI, a group of medical informatics and digital health experts, led by Laurie Lovett Novak, PhD, reported (JAMIA Open. 2023 May 3. doi: 10.1093/jamiaopen/ooad028). But it’s coming nonetheless, Dr. Novak, an associate professor of biomedical informatics at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview.

“In the near future, managers in clinics and inpatient units will be overseeing care that involves numerous AI-based technologies, including predictive analytics, imaging tools, language models, and others,” she said. “Organizations need to support managers by implementing capabilities for algorithmo-vigilance.”

That would include dealing with what she called “algorithmic drift” – when the accuracy of an AI model wanes because of changes in the underlying data – and ensuring that models are unbiased and aren’t used in a way that contributes to inequities in health care. “These new organizational capabilities will demand new tools and new competencies,” she said. That would include policies and processes drawing guidance from medical societies for legal and regulatory direction for managers, staff training, and software documentation.

Dr. Tseng envisioned how AI would work in the clinic. “I personally think that, at some time in the near future, AI-driven care coordination, where the AI basically handles appointment scheduling, patient motivation, patient engagement and acts as their health navigator, will be superior to any human health navigator on the whole, only for the reason that AI is indefatigable,” Dr. Tseng said. “It doesn’t get tired, it doesn’t get burned out, and these health navigation care coordination roles are notoriously difficult.”

The physicians and researchers interviewed for this report had no relevant relationships to disclose.

The utility of artificial intelligence in pulmonology has focused mainly on using image datasets to detect and diagnose lung malignancies, but now a growing number of AI models are emerging that apply machine learning to improve predictability for other pulmonary conditions, including pulmonary infections, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD).

These applications are moving beyond the traditional AI model of collecting data from a multitude of images to cast a wider data net that includes electronic health records.

Also on the horizon, ChatGPT technology is poised to have an impact. But pulmonologists and their practices have a number of barriers to clear before they feel a meaningful impact from AI.

The imperative, said AI researcher Ishanu Chattopadhyay, PhD, is to create transformative models that can detect lung disease early on. Dr. Chattopadhyay, an assistant professor of medicine at the University of Chicago and its Institute for Genomics and Systems Biology, and fellow researchers developed an AI algorithm that uses comorbidity signatures in electronic health records to screen for idiopathic pulmonary fibrosis (IPF) (Nature Med. 2022 Sep 29. doi: 10.1038/s41591-022-02010-y).

“If you could do this when somebody walks into a primary care setting and they are barely suspecting something is going on with them or when they don’t have the typical risk factors, there is a certain fraction of these people who do have IPF and they will almost invariably be diagnosed late and/or misdiagnosed,” Dr. Chattopadhyay said, citing a study that found 55% of patients with IPF have had at least one misdiagnosis and 38% have two or more misdiagnoses (BMC Pulm Med. 2018 Jan 17. doi: 10.1186/s12890-017-0560-x).

Harnessing massive data sets

AI models cull data sets, whether banks of radiographic images or files in an EHR, to extract telltale signatures of a disease state. Dr. Chattopadhyay and his team’s model used three databases with almost 3 million participants and 54,247 positive cases of IPF. Hospitals in Scotland have deployed what they’ve claimed are the first AI models to predict COPD built with 55,000 patient records from a regional National Health Service database. Another AI model for staging COPD, developed by researchers in the United States and Romania, used more than 18,000 medical records from 588 patients to identify physiological signals predictive of COPD (Advanced Sci. 2023 Feb 19. doi: 10.1002/advs.202203485).

Said Dr. Chattopadhyay: “If I can bring in AI which doesn’t just look at radiological images but actually gets it back where someone walks into primary care using only the information that is available at that point in the patient files and asking for nothing more, it raises a flag reliably that gets you a pulmonary referral that will hopefully reduce the misdiagnosis and late diagnosis.”

Victor Tseng, MD, medical director for pulmonology at Ansible Health in Mountain View, Calif., who’s researching the potential of AI in pulmonology, speculated on what functions AI can perform in the clinic. “I think you will start to see much more interventional sort of clinically patient care–facing applications,” he said. That would include acting as a triage layer to direct patient queries to a nurse, physician, or another practitioner, providing patient instructions, serving as therapeutic software, coordinating care, integrating supply chain issues,” he said.

 

AI vs. spirometry for COPD

Researchers in the United States and Romania, led by Paul Bogdan, PhD, at the University of Southern California Viterbi School of Engineering, developed a model that predicted COPD with an accuracy of almost 99% (98.66%) and avoids many of the shortcomings of spirometry, Dr. Bogdan said.

USC Viterbi School of Engineering

The models developed by Dr. Bogdan and collaborators use a different principle than existing AI platforms, Dr. Bogdan said. They analyze the properties of the data. As he explained it, they exploit what he called the “geometry of these data” to make inferences and decisions on a patient’s risk for COPD.

“Deep learning is very good for images, for videos, but it doesn’t work that well for signals,” said Mihai Udrescu, PhD, one of the Romanian collaborators. “But if we process the data with the technique brought up by Paul [Bogdan] and his team at USC, deep learning also works well on physiological signals.”

Dr. Paul Bogdan

Said Dr. Bogdan, “Nobody thought about using physiological signals to predict COPD before this work. They used spirometry, but spirometry is cumbersome and several steps have to be performed in order to have an accurate spirometry.” His team’s AI models extract and analyze risk data based on 10 minutes of monitoring.

This technology also has the potential to improve accessibility of COPD screening, Dr. Udrescu said. “It can democratize the access to the health care because you don’t need to travel for 100 or 200 miles to see a specialist,” he said. “You just send an app to the mobile phone of a patient, the person puts on a smart watch and wears it for a couple of minutes and the data is either recorded locally or is transmitted and it is analyzed.” The computations can be done locally and in a matter of minutes, he said.

In Scotland, a 12-month feasibility study is underway to evaluate an AI model to identify COPD patients at greatest risk for adverse events. A press release from Lenus, the company developing the technology, said the study will use a COPD multidisciplinary team to consider real-time AI model outputs to enable proactive patient encounters and reduce emergency care visits.

Researchers in Paris built an AI model that showed a 68% accuracy in distinguishing people with asthma from people with COPD in administrative medical databases (BMC Pulmon Med. 2022 Sep 20. doi: 10.1186/s12890-022-02144-2). They found that asthma patients were younger than those with COPD (a mean of 49.9 vs. 72.1 years) and that COPD occurred mostly in men (68% vs. 33%). And an international team of researchers reported that an AI model that used chest CT scans determined that ever-smokers with COPD who met the imaging criteria for bronchiectasis were more prone to disease exacerbations (Radiology. 2022 Dec 13. doi: 10.1148/radiol.221109). 

 

AI in idiopathic pulmonary fibrosis

The AI model that Dr. Chattopadhyay and collaborators developed had an 88% accuracy in predicting IPF. The model, known as the zero-burden comorbidity risk score for IPF (ZCoR-IPF), identified IPF cases in adults age 45 and older 1-4 years sooner than in a variety of pulmonology practice settings.

The model accounted for about 700 different features of IPF, Dr. Chattopadhyay said, but it deviated from standard AI risk models in that it used a machine learning algorithm to extract disease features that aren’t well understood or even known. “We do not know what all the risk factors of IPF are,” he said. “People who don’t have all the risk factors still get IPF. So we have to step back from the raw EHR data from where the features are being generated automatically, and then you can apply standard ML tools.”

Researchers at Nagoya University in Japan also reported on an AI algorithm for predicting IPF that used 646,800 high-resolution CT images and medical records data from 1,068 patients. Their algorithm had an average diagnostic accuracy of 83.6% and, they reported, demonstrated good accuracy even in patients with signs of interstitial pneumonia or who had surgical lung biopsies (Respirology. 2022 Dec 13. doi: 10.1111/resp.14310).

 

Chat GPT: The next frontier in AI

Dr. Tseng last year led a group of researchers that fed questions from the United States Medical Licensing Exam to a ChatGPT model, which found it answered 60%-65% of questions correctly (PLOS Digit Health. 2023 Feb 9. doi: 10.1371/journal.pdig.0000198). As Dr. Tseng pointed out, that’s good enough to get a medical license.

It may be a matter of time before ChatGPT technology finds its way into the clinic, Dr. Tseng said. A quick ChatGPT query of how it could be used in medicine yielded 12 different answers, from patient triage to providing basic first aid instructions in an emergency.

Dr. Tseng, who’s pulmonology practice places an emphasis on virtual care delivery, went deeper than the ChatGPT answer. “If you’re a respiratory therapist and you’re trying to execute a complicated medical care plan written by a physician, there’s a natural disconnect between our language and their language,” he said. “What we have found is that GPT has significantly harmonized the care plan. And that’s amazing because you end up with this single-stream understanding of the care plan, where the language is halfway between a bedside clinician, like the respiratory therapist or nurse, and is also something that a physician can understand and take the bigger sort of direction of care from.”

 

Barriers to AI in clinic

Numerous barriers face widespread adoption of AI tools in the clinic, Dr. Tseng said, including physician and staff anxiety about learning new technology. “AI tools, for all purposes, are supposed to allay the cognitive burden and the tedium burden on clinicians, but end up actually costing more time,” he said.

Health care organizations will also need to retool for AI, a group of medical informatics and digital health experts, led by Laurie Lovett Novak, PhD, reported (JAMIA Open. 2023 May 3. doi: 10.1093/jamiaopen/ooad028). But it’s coming nonetheless, Dr. Novak, an associate professor of biomedical informatics at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview.

“In the near future, managers in clinics and inpatient units will be overseeing care that involves numerous AI-based technologies, including predictive analytics, imaging tools, language models, and others,” she said. “Organizations need to support managers by implementing capabilities for algorithmo-vigilance.”

That would include dealing with what she called “algorithmic drift” – when the accuracy of an AI model wanes because of changes in the underlying data – and ensuring that models are unbiased and aren’t used in a way that contributes to inequities in health care. “These new organizational capabilities will demand new tools and new competencies,” she said. That would include policies and processes drawing guidance from medical societies for legal and regulatory direction for managers, staff training, and software documentation.

Dr. Tseng envisioned how AI would work in the clinic. “I personally think that, at some time in the near future, AI-driven care coordination, where the AI basically handles appointment scheduling, patient motivation, patient engagement and acts as their health navigator, will be superior to any human health navigator on the whole, only for the reason that AI is indefatigable,” Dr. Tseng said. “It doesn’t get tired, it doesn’t get burned out, and these health navigation care coordination roles are notoriously difficult.”

The physicians and researchers interviewed for this report had no relevant relationships to disclose.

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

Use current health and desire for pregnancy to guide contraception discussions in primary care, according to authors of an updated report.

In an installment of the American College of Physicians’ In the Clinic series, Rachel Cannon, MD, Kelly Treder, MD, and Elisabeth J. Woodhams, MD, all of Boston Medical Center, presented an article on the complex topic of contraception for patients with chronic illness.

“Many patients with chronic illness or complex medical issues interact with a primary care provider on a frequent basis, which provides a great access point for contraceptive counseling with a provider they trust and know,” said Dr. Cannon and Dr. Treder in a joint interview. “We wanted to create a ‘go to’ resource for primary care physicians to review contraceptive options and counseling best practices for all of their patients. Contraceptive care is part of overall health care and should be included in the primary care encounter.”

The authors discussed the types of contraception, as well as risks and benefits, and offered guidance for choosing a contraceptive method for medically complex patients.

“In recent years, there has been a shift in contraceptive counseling toward shared decision-making, a counseling strategy that honors the patient as the expert in their body and their life experiences and emphasizes their autonomy and values,” the authors said. “For providers, this translates to understanding that contraceptive efficacy is not the only important characteristic to patients, and that many other important factors contribute to an individual’s decision to use a particular method or not use birth control at all,” they said.
 

Start the conversation

Start by assessing a patient’s interest in and readiness for pregnancy, if applicable, the authors said. One example of a screen, the PATH questionnaire (Parent/Pregnancy Attitudes, Timing, and How important), is designed for patients in any demographic, and includes questions about the timing and desire for pregnancy and feelings about birth control, as well as options for patients to express uncertainty or ambivalence about pregnancy and contraception.

Some patients may derive benefits from hormonal contraceptives beyond pregnancy prevention, the authors wrote. Combined hormonal contraceptives (CHCs) may improve menorrhagia, and data suggest that CHC use also may reduce risk for some cancer types, including endometrial and ovarian cancers, they said.

Overall, contraceptive counseling should include discussions of safety, efficacy, and the patient’s lived experience.
 

Clinical considerations and contraindications

Medically complex patients who desire contraception may consider hormonal or nonhormonal methods based on their preferences and medical conditions, but clinicians need to consider comorbidities and contraindications, the authors wrote.

When a woman of childbearing age with any complex medical issue starts a new medication or receives a new diagnosis, contraception and pregnancy planning should be part of the discussion, the authors said. Safe and successful pregnancies are possible for women with complex medical issues when underlying health concerns are identified and addressed in advance, they added. Alternatively, for patients seeking to avoid pregnancy permanently, options for sterilization can be part of an informed discussion.

The Centers for Disease Control and Prevention’s Medical Eligibility Criteria for Contraceptive Use offers clinicians detailed information about the risks of both contraceptives and pregnancy for patients with various medical conditions, according to the authors.

The CDC document lists medical conditions associated with an increased risk for adverse health events if the individual becomes pregnant. These conditions include breast cancer, complicated valvular heart disease, cystic fibrosis, diabetes, endometrial or ovarian cancer, epilepsy, hypertension, bariatric surgery within 2 years of the pregnancy, HIV, ischemic heart disease, severe cirrhosis, stroke, lupus, solid organ transplant within 2 years of the pregnancy, and tuberculosis. Women with these and other conditions associated with increased risk of adverse events if pregnancy occurs should be advised of the high failure rate of barrier and behavior-based contraceptive methods, and informed about options for long-acting contraceptives, according to the CDC.
 

Risks, benefits, and balance

“It is important to remember that the alternative to contraception for many patients is pregnancy – for many patients with complex medical conditions, pregnancy is far more dangerous than any contraceptive method,” Dr. Cannon and Dr. Treder said in an interview. “This is important to consider when thinking about relative contraindications to a certain method or when thinking about ‘less effective’ contraception methods. The most effective method is a method the patient will actually continue to use,” they said.

The recent approval of the over-the-counter minipill is “a huge win for reproductive health care,” said Dr. Cannon and Dr. Treder. The minipill has very few contraindications, and it is the most effective over-the-counter contraceptive now available, they said.

“An over-the-counter contraceptive pill can increase access to contraception without having to see a physician in the clinic, freeing patients from many of the challenges of navigating the health care system,” the authors added.

As for additional research, the establishment of a long-term safety record may help support other OTC contraceptive methods in the future, the authors said.
 

Contraceptive counseling is everyone’s specialty

In an accompanying editorial, Amy A. Sarma, MD, a cardiologist at Massachusetts General Hospital, Boston, shared an example of the importance of contraceptive discussions with medically complex patients outside of an ob.gyn. setting. A young woman with a family history of myocardial infarction had neglected her own primary care until an MI of her own sent her to the hospital. While hospitalized, the patient was diagnosed with diabetes, hypertension, and hyperlipidemia.

“Her cardiology care team made every effort to optimize her cardiac care, but no one considered that she was also a woman of childbearing potential despite the teratogenic potential of several of her prescribed medications,” Dr. Sarma wrote. When the patient visited Dr. Sarma to discuss prevention of future MIs, Dr. Sarma took the opportunity to discuss the cardiovascular risks of pregnancy and the risks for this patient not only because of her recent MI, but also because of her chronic health conditions.

As it happened, the woman did not want a high-risk pregnancy and was interested in contraceptive methods. Dr. Sarma pointed out that, had the woman been engaged in routine primary care, these issues would have arisen in that setting, but like many younger women with cardiovascular disease, she did not make her own primary care a priority, and had missed out on other opportunities to discuss contraception. “Her MI opened a window of opportunity to help prevent an unintended and high-risk pregnancy,” Dr. Sarma noted.

Dr. Sarma’s patient anecdote illustrated the point of the In the Clinic review: that any clinician can discuss pregnancy and contraception with patients of childbearing age who have medical comorbidities that could affect a pregnancy. “All clinicians who care for patients of reproductive potential should become comfortable discussing pregnancy intent, preconception risk assessment, and contraceptive counseling,” Dr. Sarma said.

The research for this article was funded by the American College of Physicians. The review authors had no financial conflicts to disclose. Dr. Sarma had no financial conflicts to disclose.

Use current health and desire for pregnancy to guide contraception discussions in primary care, according to authors of an updated report.

In an installment of the American College of Physicians’ In the Clinic series, Rachel Cannon, MD, Kelly Treder, MD, and Elisabeth J. Woodhams, MD, all of Boston Medical Center, presented an article on the complex topic of contraception for patients with chronic illness.

“Many patients with chronic illness or complex medical issues interact with a primary care provider on a frequent basis, which provides a great access point for contraceptive counseling with a provider they trust and know,” said Dr. Cannon and Dr. Treder in a joint interview. “We wanted to create a ‘go to’ resource for primary care physicians to review contraceptive options and counseling best practices for all of their patients. Contraceptive care is part of overall health care and should be included in the primary care encounter.”

The authors discussed the types of contraception, as well as risks and benefits, and offered guidance for choosing a contraceptive method for medically complex patients.

“In recent years, there has been a shift in contraceptive counseling toward shared decision-making, a counseling strategy that honors the patient as the expert in their body and their life experiences and emphasizes their autonomy and values,” the authors said. “For providers, this translates to understanding that contraceptive efficacy is not the only important characteristic to patients, and that many other important factors contribute to an individual’s decision to use a particular method or not use birth control at all,” they said.
 

Start the conversation

Start by assessing a patient’s interest in and readiness for pregnancy, if applicable, the authors said. One example of a screen, the PATH questionnaire (Parent/Pregnancy Attitudes, Timing, and How important), is designed for patients in any demographic, and includes questions about the timing and desire for pregnancy and feelings about birth control, as well as options for patients to express uncertainty or ambivalence about pregnancy and contraception.

Some patients may derive benefits from hormonal contraceptives beyond pregnancy prevention, the authors wrote. Combined hormonal contraceptives (CHCs) may improve menorrhagia, and data suggest that CHC use also may reduce risk for some cancer types, including endometrial and ovarian cancers, they said.

Overall, contraceptive counseling should include discussions of safety, efficacy, and the patient’s lived experience.
 

Clinical considerations and contraindications

Medically complex patients who desire contraception may consider hormonal or nonhormonal methods based on their preferences and medical conditions, but clinicians need to consider comorbidities and contraindications, the authors wrote.

When a woman of childbearing age with any complex medical issue starts a new medication or receives a new diagnosis, contraception and pregnancy planning should be part of the discussion, the authors said. Safe and successful pregnancies are possible for women with complex medical issues when underlying health concerns are identified and addressed in advance, they added. Alternatively, for patients seeking to avoid pregnancy permanently, options for sterilization can be part of an informed discussion.

The Centers for Disease Control and Prevention’s Medical Eligibility Criteria for Contraceptive Use offers clinicians detailed information about the risks of both contraceptives and pregnancy for patients with various medical conditions, according to the authors.

The CDC document lists medical conditions associated with an increased risk for adverse health events if the individual becomes pregnant. These conditions include breast cancer, complicated valvular heart disease, cystic fibrosis, diabetes, endometrial or ovarian cancer, epilepsy, hypertension, bariatric surgery within 2 years of the pregnancy, HIV, ischemic heart disease, severe cirrhosis, stroke, lupus, solid organ transplant within 2 years of the pregnancy, and tuberculosis. Women with these and other conditions associated with increased risk of adverse events if pregnancy occurs should be advised of the high failure rate of barrier and behavior-based contraceptive methods, and informed about options for long-acting contraceptives, according to the CDC.
 

Risks, benefits, and balance

“It is important to remember that the alternative to contraception for many patients is pregnancy – for many patients with complex medical conditions, pregnancy is far more dangerous than any contraceptive method,” Dr. Cannon and Dr. Treder said in an interview. “This is important to consider when thinking about relative contraindications to a certain method or when thinking about ‘less effective’ contraception methods. The most effective method is a method the patient will actually continue to use,” they said.

The recent approval of the over-the-counter minipill is “a huge win for reproductive health care,” said Dr. Cannon and Dr. Treder. The minipill has very few contraindications, and it is the most effective over-the-counter contraceptive now available, they said.

“An over-the-counter contraceptive pill can increase access to contraception without having to see a physician in the clinic, freeing patients from many of the challenges of navigating the health care system,” the authors added.

As for additional research, the establishment of a long-term safety record may help support other OTC contraceptive methods in the future, the authors said.
 

Contraceptive counseling is everyone’s specialty

In an accompanying editorial, Amy A. Sarma, MD, a cardiologist at Massachusetts General Hospital, Boston, shared an example of the importance of contraceptive discussions with medically complex patients outside of an ob.gyn. setting. A young woman with a family history of myocardial infarction had neglected her own primary care until an MI of her own sent her to the hospital. While hospitalized, the patient was diagnosed with diabetes, hypertension, and hyperlipidemia.

“Her cardiology care team made every effort to optimize her cardiac care, but no one considered that she was also a woman of childbearing potential despite the teratogenic potential of several of her prescribed medications,” Dr. Sarma wrote. When the patient visited Dr. Sarma to discuss prevention of future MIs, Dr. Sarma took the opportunity to discuss the cardiovascular risks of pregnancy and the risks for this patient not only because of her recent MI, but also because of her chronic health conditions.

As it happened, the woman did not want a high-risk pregnancy and was interested in contraceptive methods. Dr. Sarma pointed out that, had the woman been engaged in routine primary care, these issues would have arisen in that setting, but like many younger women with cardiovascular disease, she did not make her own primary care a priority, and had missed out on other opportunities to discuss contraception. “Her MI opened a window of opportunity to help prevent an unintended and high-risk pregnancy,” Dr. Sarma noted.

Dr. Sarma’s patient anecdote illustrated the point of the In the Clinic review: that any clinician can discuss pregnancy and contraception with patients of childbearing age who have medical comorbidities that could affect a pregnancy. “All clinicians who care for patients of reproductive potential should become comfortable discussing pregnancy intent, preconception risk assessment, and contraceptive counseling,” Dr. Sarma said.

The research for this article was funded by the American College of Physicians. The review authors had no financial conflicts to disclose. Dr. Sarma had no financial conflicts to disclose.

Use current health and desire for pregnancy to guide contraception discussions in primary care, according to authors of an updated report.

In an installment of the American College of Physicians’ In the Clinic series, Rachel Cannon, MD, Kelly Treder, MD, and Elisabeth J. Woodhams, MD, all of Boston Medical Center, presented an article on the complex topic of contraception for patients with chronic illness.

“Many patients with chronic illness or complex medical issues interact with a primary care provider on a frequent basis, which provides a great access point for contraceptive counseling with a provider they trust and know,” said Dr. Cannon and Dr. Treder in a joint interview. “We wanted to create a ‘go to’ resource for primary care physicians to review contraceptive options and counseling best practices for all of their patients. Contraceptive care is part of overall health care and should be included in the primary care encounter.”

The authors discussed the types of contraception, as well as risks and benefits, and offered guidance for choosing a contraceptive method for medically complex patients.

“In recent years, there has been a shift in contraceptive counseling toward shared decision-making, a counseling strategy that honors the patient as the expert in their body and their life experiences and emphasizes their autonomy and values,” the authors said. “For providers, this translates to understanding that contraceptive efficacy is not the only important characteristic to patients, and that many other important factors contribute to an individual’s decision to use a particular method or not use birth control at all,” they said.
 

Start the conversation

Start by assessing a patient’s interest in and readiness for pregnancy, if applicable, the authors said. One example of a screen, the PATH questionnaire (Parent/Pregnancy Attitudes, Timing, and How important), is designed for patients in any demographic, and includes questions about the timing and desire for pregnancy and feelings about birth control, as well as options for patients to express uncertainty or ambivalence about pregnancy and contraception.

Some patients may derive benefits from hormonal contraceptives beyond pregnancy prevention, the authors wrote. Combined hormonal contraceptives (CHCs) may improve menorrhagia, and data suggest that CHC use also may reduce risk for some cancer types, including endometrial and ovarian cancers, they said.

Overall, contraceptive counseling should include discussions of safety, efficacy, and the patient’s lived experience.
 

Clinical considerations and contraindications

Medically complex patients who desire contraception may consider hormonal or nonhormonal methods based on their preferences and medical conditions, but clinicians need to consider comorbidities and contraindications, the authors wrote.

When a woman of childbearing age with any complex medical issue starts a new medication or receives a new diagnosis, contraception and pregnancy planning should be part of the discussion, the authors said. Safe and successful pregnancies are possible for women with complex medical issues when underlying health concerns are identified and addressed in advance, they added. Alternatively, for patients seeking to avoid pregnancy permanently, options for sterilization can be part of an informed discussion.

The Centers for Disease Control and Prevention’s Medical Eligibility Criteria for Contraceptive Use offers clinicians detailed information about the risks of both contraceptives and pregnancy for patients with various medical conditions, according to the authors.

The CDC document lists medical conditions associated with an increased risk for adverse health events if the individual becomes pregnant. These conditions include breast cancer, complicated valvular heart disease, cystic fibrosis, diabetes, endometrial or ovarian cancer, epilepsy, hypertension, bariatric surgery within 2 years of the pregnancy, HIV, ischemic heart disease, severe cirrhosis, stroke, lupus, solid organ transplant within 2 years of the pregnancy, and tuberculosis. Women with these and other conditions associated with increased risk of adverse events if pregnancy occurs should be advised of the high failure rate of barrier and behavior-based contraceptive methods, and informed about options for long-acting contraceptives, according to the CDC.
 

Risks, benefits, and balance

“It is important to remember that the alternative to contraception for many patients is pregnancy – for many patients with complex medical conditions, pregnancy is far more dangerous than any contraceptive method,” Dr. Cannon and Dr. Treder said in an interview. “This is important to consider when thinking about relative contraindications to a certain method or when thinking about ‘less effective’ contraception methods. The most effective method is a method the patient will actually continue to use,” they said.

The recent approval of the over-the-counter minipill is “a huge win for reproductive health care,” said Dr. Cannon and Dr. Treder. The minipill has very few contraindications, and it is the most effective over-the-counter contraceptive now available, they said.

“An over-the-counter contraceptive pill can increase access to contraception without having to see a physician in the clinic, freeing patients from many of the challenges of navigating the health care system,” the authors added.

As for additional research, the establishment of a long-term safety record may help support other OTC contraceptive methods in the future, the authors said.
 

Contraceptive counseling is everyone’s specialty

In an accompanying editorial, Amy A. Sarma, MD, a cardiologist at Massachusetts General Hospital, Boston, shared an example of the importance of contraceptive discussions with medically complex patients outside of an ob.gyn. setting. A young woman with a family history of myocardial infarction had neglected her own primary care until an MI of her own sent her to the hospital. While hospitalized, the patient was diagnosed with diabetes, hypertension, and hyperlipidemia.

“Her cardiology care team made every effort to optimize her cardiac care, but no one considered that she was also a woman of childbearing potential despite the teratogenic potential of several of her prescribed medications,” Dr. Sarma wrote. When the patient visited Dr. Sarma to discuss prevention of future MIs, Dr. Sarma took the opportunity to discuss the cardiovascular risks of pregnancy and the risks for this patient not only because of her recent MI, but also because of her chronic health conditions.

As it happened, the woman did not want a high-risk pregnancy and was interested in contraceptive methods. Dr. Sarma pointed out that, had the woman been engaged in routine primary care, these issues would have arisen in that setting, but like many younger women with cardiovascular disease, she did not make her own primary care a priority, and had missed out on other opportunities to discuss contraception. “Her MI opened a window of opportunity to help prevent an unintended and high-risk pregnancy,” Dr. Sarma noted.

Dr. Sarma’s patient anecdote illustrated the point of the In the Clinic review: that any clinician can discuss pregnancy and contraception with patients of childbearing age who have medical comorbidities that could affect a pregnancy. “All clinicians who care for patients of reproductive potential should become comfortable discussing pregnancy intent, preconception risk assessment, and contraceptive counseling,” Dr. Sarma said.

The research for this article was funded by the American College of Physicians. The review authors had no financial conflicts to disclose. Dr. Sarma had no financial conflicts to disclose.

FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?

This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.

In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
 

A visionary view

In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].

In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.

This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.

And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.

“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”

He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.

A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.

But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.

On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.

“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.

But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.

“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.

But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”

Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”

In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”

Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
 

Wealth of knowledge

Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.

That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.

The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?

This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.

In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
 

A visionary view

In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].

In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.

This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.

And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.

“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”

He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.

A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.

But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.

On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.

“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.

But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.

“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.

But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”

Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”

In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”

Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
 

Wealth of knowledge

Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.

That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.

The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?

This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.

In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
 

A visionary view

In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].

In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.

This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.

And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.

“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”

He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.

A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.

But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.

On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.

“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.

But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.

“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.

But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”

Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”

In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”

Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
 

Wealth of knowledge

Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.

That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.

The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

For the first time, the Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Several experts in mental health and women’s health offered their views of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms such as hopelessness, crankiness, and lack of interest in bonding with the baby or, in the case of multiples, babies – and in some cases, thoughts of death or suicide?
 

A fast-acting option

“We don’t have many oral medications that are fast-acting antidepressants, so this is incredibly exciting,” said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants – it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

“It’s obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications,” said Kimberly Yonkers, MD, a psychiatrist specializing in women’s health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, “typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression,” said Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Dr. Oreck said. “We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression,” she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Dr. Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

“It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families,” said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times – during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Dr. Zahn added.

The cost of zuranolone is not yet known. Dr. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. “Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access.”
 

Beyond ‘baby blues’

The APA has changed the name from “postpartum depression” to “peripartum depression” because evidence suggests feelings and symptoms also can start late in pregnancy. “It means you don’t have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy,” Dr. Yonkers said. “In fact it is not uncommon during the third trimester.”

No matter when it starts, the condition can be “very serious,” particularly if the person already experiences depression, including bipolar disorder, Dr. Yonkers added.

Postpartum depression “is more than just ‘baby blues.’ It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn,” Dr. Gopalan said.
 

Can be a medical emergency

Severe postpartum depression requires immediate attention and treatment.

“One of the things we have to be cautious about is for people with previous predisposition to hurt themselves,” Dr. Yonkers said. “It is therefore important to consider somebody’s medical and behavioral health history as well.

“For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy,” Dr. Yonkers said. “They may need ongoing antidepressants.

“It may not be the right pill for everybody,” Dr. Yonkers added. She recommended everyone be followed closely during and after treatment “to make sure they are responding and to monitor for relapse.”
 

The science that led to approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days “showed significantly more improvement in their symptoms compared to those in the placebo group.”

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person’s ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.
 

The start of more help for mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Dr. Gopalan said.

Dr. Oreck said she hopes this first pill approval will lead to more discoveries. “I hope this is the beginning of more innovation and development of novel treatments that can target women’s mental health issues specifically – female reproductive hormones impact mental health in unique ways and it’s exciting to finally see research and development dollars dedicated to them,” she said. “The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression.”

Dr. Oreck, Dr. Yonkers, Dr. Gopalan, and Dr. Zahn have disclosed no relevant financial relationships.
 

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

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Treatment options for patients with cancer that is detected at a late stage are severely limited, which usually leads to an unfavorable prognosis for such patients. Indeed, the options available for patients with metastatic solid cancers are scarcely curative. Therefore, early diagnosis of neoplasia remains a fundamental mainstay for improving outcomes for cancer patients.

Histopathology is the current gold standard for cancer diagnosis. Biopsy is an invasive procedure that provides physicians with further samples to test but that furnishes limited information concerning tumor heterogeneity. Biopsy specimens are usually obtained only when there is clinical evidence of neoplasia, which significantly limits their usefulness in early diagnosis.

Around 20 years ago, it was discovered that the presence of circulating tumor cells (CTC) in patients with metastatic breast cancer who were about to begin a new line of treatment was predictive of overall and progression-free survival. The prognostic value of CTC was independent of the line of treatment (first or second) and was greater than that of the site of metastasis, the type of therapy, and the time to metastasis after complete primary resection. These results support the idea that the presence of CTC could be used to modify the system for staging advanced disease.

Since then, research into liquid biopsy assays has expanded rapidly, and many biomarkers have been studied in various body fluids for their usefulness in assessing solid tumors.
 

Liquid vs. tissue

Liquid biopsy is a minimally invasive tool that is easy to use. It is employed to detect cancer, to assess treatment response, or to monitor disease progression. Liquid biopsy produces test material from primary and metastatic (or micrometastatic) sites and provides a more heterogeneous picture of the entire tumor cell population, compared with specimens obtained with tissue biopsy.

Metastasis

The notion that metastatic lesions are formed from cancer cells that have disseminated from advanced primary tumors has been substantially revised following the identification of disseminated tumor cells (DTC) in the bone marrow of patients with early-stage disease. These results have led researchers to no longer view cancer metastasis as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as metastasizing cells assume new phenotypes while abandoning older behaviors.

The initiation of metastasis is not simply a cell-autonomous event but is heavily influenced by complex tissue microenvironments. Although colonization of distant tissues by DTC is an extremely inefficient process, at times, relatively numerous CTC can be detected in the blood of cancer patients (> 1,000 CTC/mL of blood plasma), whereas the number of clinically detectable metastases is disproportionately low, confirming that tumor cell diffusion can happen at an early stage but usually occurs later on.
 

Early dissemination

Little is currently known about the preference of cancer subtypes for distinct tissues or about the receptiveness of a tissue as a metastatic site. What endures as one of the most confounding clinical phenomena is that patients may undergo tumor resection and remain apparently disease free for months, years, and even decades, only to experience relapse and be diagnosed with late-stage metastatic disease. This course may be a result of cell seeding from minimal residual disease after resection of the primary tumor or of preexisting clinically undetectable micrometastases. It may also arise from early disseminated cells that remain dormant and resistant to therapy until they suddenly reawaken to initiate proliferation into clinically detectable macrometastases.

Dormant DTC could be the main reason for delayed detection of metastases. It is thought that around 40% of patients with prostate cancer who undergo radical prostatectomy present with biochemical recurrence, suggesting that it is likely that hidden DTC or micrometastases are present at the time of the procedure. The finding is consistent with the detection of DTC many years after tumor resection, suggesting they were released before surgical treatment. Nevertheless, research into tumor cell dormancy is limited, owing to the invasive and technically challenging nature of obtaining DTC samples, which are predominantly taken from the bone marrow.
 

CTC metastases

Cancer cells can undergo epithelial-to-mesenchymal transition to facilitate their detachment from the primary tumor and intravasation into the blood circulation (step 1). Dissemination of cancer cells from the primary tumor into circulation can involve either single cells or cell clusters containing multiple CTC as well as immune cells and platelets, known as microemboli. CTC that can survive in circulation (step 2) can exit the bloodstream (step 3) and establish metastatic tumors (step 4), or they can enter dormancy and reside in distant organs, such as the bone marrow.

Use in practice

CTC were discovered over a century ago, but only in recent years has technology been sufficiently advanced to study CTC and to assess their usefulness as biomarkers. Recent evidence suggests that not only do the number of CTC increase during sleep and rest phases but also that these CTC are better able to metastasize, compared to those generated during periods of wakefulness or activity.

CTC clusters (microemboli) are defined as groups of two or more CTC. They can consist of CTC alone (homotypic) or can include various stromal cells, such as cancer-associated fibroblasts or platelets and immune cells (heterotypic). CTC clusters (with or without leukocytes) seem to have greater metastatic capacity, compared with individual CTC.

A multitude of characteristics can be measured in CTC, including genetics and epigenetics, as well as protein levels, which might help in understanding many processes involved in the formation of metastases.

Quantitative assessment of CTC could indicate tumor burden in patients with aggressive cancers, as has been seen in patients with primary lung cancer.
 

Early cancer diagnosis

Early research into CTC didn’t explore their usefulness in diagnosing early-stage tumors because it was thought that CTC were characteristic of advanced-stage disease. This hypothesis was later rejected following evidence of local intravascular invasion of very early cancer cells, even over a period of several hours. This feature may allow CTC to be detected before the clinical diagnosis of cancer.

CTC have been detected in various neoplastic conditions: in breast cancer, seen in 20% of patients with stage I disease, in 26.8% with stage II disease, and 26.7% with stage III disease; in nonmetastatic colorectal cancer, including stage I and II disease; and in prostate cancer, seen in over 50% of patients with localized disease.

The presence of CTC has been proven to be an unfavorable prognostic predictor of overall survival among patients with early-stage non–small cell lung cancer. It distinguishes patients with pancreatic ductal adenocarcinoma from those with noncancerous pancreatic diseases with a sensitivity of 75% and a specificity of 96.3%.

CTC positivity scoring (appropriately defined), combined with serum prostate-specific antigen level, was predictive of a biopsy diagnosis of clinically significant prostate cancer.

All these data support the utility of CTC in early cancer diagnosis. Their link with metastases, and thus with aggressive tumors, gives them an advantage over other (noninvasive or minimally invasive) biomarkers in the early identification of invasive tumors for therapeutic intervention with better cure rates.
 

This article was translated from Univadis Italy. A version appeared on Medscape.com.