User login
New AGA CPU focuses on gastric peroral endoscopic myotomy for gastroparesis
Authored by Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Medicine, Baltimore; Andrew Y. Wang, MD, AGAF, chief of interventional endoscopy, University of Virginia, Charlottesville; and, Qiang Cai, MD, PhD, chief of gastroenterology, Ochsner LSU Health Shreveport (La.), the update covers patient selection, procedural considerations, adverse events (AEs), and other topics.
“G-POEM is being performed worldwide to treat patients with refractory gastroparesis,” the investigators wrote in Gastroenterology). “G-POEM is an overall safe procedure with high technical success rates, particularly when performed by an endoscopist experienced in third-space endoscopy. Even if the durable clinical success of G-POEM is in the 50% to 60% range, this represents a huge clinical benefit to patients with refractory gastroparesis, which is a disease associated with substantial morbidity, poor quality of life, and a paucity of safe and effective treatments.”
The authors listed treatment alternatives, noting how associated clinical data have fallen short.
“Although endoscopic pyloric balloon dilation, intrapyloric botulinum toxin injection, gastric electrical stimulation, and transpyloric stenting have been used in patients [with gastroparesis] who have not responded to medical therapy, published studies concerning these therapies have been inconsistent, shown no benefit, or lacked methodologic rigor,” they wrote.
Patient selection
G-POEM should be considered in patients with medically refractory gastroparesis due to diabetes, prior surgery, or idiopathic causes. Candidates should undergo endoscopy to confirm no mechanical obstruction, as well as a solid-phase gastric emptying scan to confirm delayed emptying, with ideal candidates showing at least 20% retention at 4 hours, as this threshold has been linked with better clinical outcomes.
G-POEM is most beneficial when moderate to severe symptoms are present, the investigators wrote, particularly vomiting and nausea. The Gastroparesis Cardinal Symptom Index (GCSI) can be used to determine severity, with a score greater than 2 indicating moderate to severe presentation.
Procedural considerations
The CPU offers detailed procedural considerations, including preparation and equipment, technical guidance, and postprocedural strategy.
“G-POEM should only be performed by interventional endoscopists with expertise or training in third-space endoscopy,” Dr. Khashab and colleagues wrote. “Although experience in endoscopic submucosal dissection (ESD) is not mandatory before performing G-POEM, it likely shortens the learning curve.”
Equipment minimums are also described, including “a high-definition gastroscope, with a waterjet, affixed with a clear distal cap” and “a modern electrosurgical generator capable of modulating power based on tissue resistance and circuit impedance.”
While G-POEM is typically performed via a greater-curvature approach, similar outcomes have been documented for a lesser-curvature approach, Dr. Khashab and colleagues wrote. This alternative technique may increase difficulty of pyloromyotomy, they added.
Postprocedural care may involve an overnight stay, according to the update, with an upper GI study on the subsequent day to ensure no contrast leakage, though this is not mandatory.
Adverse events
“G-POEM is generally safe when performed by trained and/or experienced endoscopists, and AEs are uncommon,” the investigators wrote. “However, serious AEs can occur and have been reported.”
Reported AEs include capnoperitoneum, inadvertent mucosotomy, thermal-mucosal injury, abdominal pain, bleeding, gastric ulceration, and dumping syndrome.
Insurance companies called to action
After reviewing emerging data, the authors suggested the time has come to consider G-POEM as a routine, evidence-based procedure that deserves appropriate reimbursement by financial stakeholders.
“Many insurers still consider G-POEM investigational and refuse to cover this procedure for patients with medically refractory gastroparesis,” they wrote. “As the safety and clinical effectiveness of G-POEM is now well supported, insurance companies and payors should cover G-POEM for patients with significant gastroparesis.”
The clinical practice update was commissioned and approved by the American Gastroenterological Association. The investigators disclosed relationships with Boston Scientific, Medtronic, and Olympus, among others.
Authored by Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Medicine, Baltimore; Andrew Y. Wang, MD, AGAF, chief of interventional endoscopy, University of Virginia, Charlottesville; and, Qiang Cai, MD, PhD, chief of gastroenterology, Ochsner LSU Health Shreveport (La.), the update covers patient selection, procedural considerations, adverse events (AEs), and other topics.
“G-POEM is being performed worldwide to treat patients with refractory gastroparesis,” the investigators wrote in Gastroenterology). “G-POEM is an overall safe procedure with high technical success rates, particularly when performed by an endoscopist experienced in third-space endoscopy. Even if the durable clinical success of G-POEM is in the 50% to 60% range, this represents a huge clinical benefit to patients with refractory gastroparesis, which is a disease associated with substantial morbidity, poor quality of life, and a paucity of safe and effective treatments.”
The authors listed treatment alternatives, noting how associated clinical data have fallen short.
“Although endoscopic pyloric balloon dilation, intrapyloric botulinum toxin injection, gastric electrical stimulation, and transpyloric stenting have been used in patients [with gastroparesis] who have not responded to medical therapy, published studies concerning these therapies have been inconsistent, shown no benefit, or lacked methodologic rigor,” they wrote.
Patient selection
G-POEM should be considered in patients with medically refractory gastroparesis due to diabetes, prior surgery, or idiopathic causes. Candidates should undergo endoscopy to confirm no mechanical obstruction, as well as a solid-phase gastric emptying scan to confirm delayed emptying, with ideal candidates showing at least 20% retention at 4 hours, as this threshold has been linked with better clinical outcomes.
G-POEM is most beneficial when moderate to severe symptoms are present, the investigators wrote, particularly vomiting and nausea. The Gastroparesis Cardinal Symptom Index (GCSI) can be used to determine severity, with a score greater than 2 indicating moderate to severe presentation.
Procedural considerations
The CPU offers detailed procedural considerations, including preparation and equipment, technical guidance, and postprocedural strategy.
“G-POEM should only be performed by interventional endoscopists with expertise or training in third-space endoscopy,” Dr. Khashab and colleagues wrote. “Although experience in endoscopic submucosal dissection (ESD) is not mandatory before performing G-POEM, it likely shortens the learning curve.”
Equipment minimums are also described, including “a high-definition gastroscope, with a waterjet, affixed with a clear distal cap” and “a modern electrosurgical generator capable of modulating power based on tissue resistance and circuit impedance.”
While G-POEM is typically performed via a greater-curvature approach, similar outcomes have been documented for a lesser-curvature approach, Dr. Khashab and colleagues wrote. This alternative technique may increase difficulty of pyloromyotomy, they added.
Postprocedural care may involve an overnight stay, according to the update, with an upper GI study on the subsequent day to ensure no contrast leakage, though this is not mandatory.
Adverse events
“G-POEM is generally safe when performed by trained and/or experienced endoscopists, and AEs are uncommon,” the investigators wrote. “However, serious AEs can occur and have been reported.”
Reported AEs include capnoperitoneum, inadvertent mucosotomy, thermal-mucosal injury, abdominal pain, bleeding, gastric ulceration, and dumping syndrome.
Insurance companies called to action
After reviewing emerging data, the authors suggested the time has come to consider G-POEM as a routine, evidence-based procedure that deserves appropriate reimbursement by financial stakeholders.
“Many insurers still consider G-POEM investigational and refuse to cover this procedure for patients with medically refractory gastroparesis,” they wrote. “As the safety and clinical effectiveness of G-POEM is now well supported, insurance companies and payors should cover G-POEM for patients with significant gastroparesis.”
The clinical practice update was commissioned and approved by the American Gastroenterological Association. The investigators disclosed relationships with Boston Scientific, Medtronic, and Olympus, among others.
Authored by Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Medicine, Baltimore; Andrew Y. Wang, MD, AGAF, chief of interventional endoscopy, University of Virginia, Charlottesville; and, Qiang Cai, MD, PhD, chief of gastroenterology, Ochsner LSU Health Shreveport (La.), the update covers patient selection, procedural considerations, adverse events (AEs), and other topics.
“G-POEM is being performed worldwide to treat patients with refractory gastroparesis,” the investigators wrote in Gastroenterology). “G-POEM is an overall safe procedure with high technical success rates, particularly when performed by an endoscopist experienced in third-space endoscopy. Even if the durable clinical success of G-POEM is in the 50% to 60% range, this represents a huge clinical benefit to patients with refractory gastroparesis, which is a disease associated with substantial morbidity, poor quality of life, and a paucity of safe and effective treatments.”
The authors listed treatment alternatives, noting how associated clinical data have fallen short.
“Although endoscopic pyloric balloon dilation, intrapyloric botulinum toxin injection, gastric electrical stimulation, and transpyloric stenting have been used in patients [with gastroparesis] who have not responded to medical therapy, published studies concerning these therapies have been inconsistent, shown no benefit, or lacked methodologic rigor,” they wrote.
Patient selection
G-POEM should be considered in patients with medically refractory gastroparesis due to diabetes, prior surgery, or idiopathic causes. Candidates should undergo endoscopy to confirm no mechanical obstruction, as well as a solid-phase gastric emptying scan to confirm delayed emptying, with ideal candidates showing at least 20% retention at 4 hours, as this threshold has been linked with better clinical outcomes.
G-POEM is most beneficial when moderate to severe symptoms are present, the investigators wrote, particularly vomiting and nausea. The Gastroparesis Cardinal Symptom Index (GCSI) can be used to determine severity, with a score greater than 2 indicating moderate to severe presentation.
Procedural considerations
The CPU offers detailed procedural considerations, including preparation and equipment, technical guidance, and postprocedural strategy.
“G-POEM should only be performed by interventional endoscopists with expertise or training in third-space endoscopy,” Dr. Khashab and colleagues wrote. “Although experience in endoscopic submucosal dissection (ESD) is not mandatory before performing G-POEM, it likely shortens the learning curve.”
Equipment minimums are also described, including “a high-definition gastroscope, with a waterjet, affixed with a clear distal cap” and “a modern electrosurgical generator capable of modulating power based on tissue resistance and circuit impedance.”
While G-POEM is typically performed via a greater-curvature approach, similar outcomes have been documented for a lesser-curvature approach, Dr. Khashab and colleagues wrote. This alternative technique may increase difficulty of pyloromyotomy, they added.
Postprocedural care may involve an overnight stay, according to the update, with an upper GI study on the subsequent day to ensure no contrast leakage, though this is not mandatory.
Adverse events
“G-POEM is generally safe when performed by trained and/or experienced endoscopists, and AEs are uncommon,” the investigators wrote. “However, serious AEs can occur and have been reported.”
Reported AEs include capnoperitoneum, inadvertent mucosotomy, thermal-mucosal injury, abdominal pain, bleeding, gastric ulceration, and dumping syndrome.
Insurance companies called to action
After reviewing emerging data, the authors suggested the time has come to consider G-POEM as a routine, evidence-based procedure that deserves appropriate reimbursement by financial stakeholders.
“Many insurers still consider G-POEM investigational and refuse to cover this procedure for patients with medically refractory gastroparesis,” they wrote. “As the safety and clinical effectiveness of G-POEM is now well supported, insurance companies and payors should cover G-POEM for patients with significant gastroparesis.”
The clinical practice update was commissioned and approved by the American Gastroenterological Association. The investigators disclosed relationships with Boston Scientific, Medtronic, and Olympus, among others.
FROM GASTROENTEROLOGY
How not to establish rapport with your patient
1. Stride confidently into the room to greet your 84-year-old female patient.
2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”
3. Extend your clenched fist toward her chest and wait for her to reciprocate.
4. Smile awkwardly behind your mask while you wait.
5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.
6. Wait.
7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.
8. Wait a bit more.
9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.
10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.
It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.
There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.
Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.
The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).
With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
1. Stride confidently into the room to greet your 84-year-old female patient.
2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”
3. Extend your clenched fist toward her chest and wait for her to reciprocate.
4. Smile awkwardly behind your mask while you wait.
5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.
6. Wait.
7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.
8. Wait a bit more.
9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.
10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.
It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.
There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.
Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.
The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).
With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
1. Stride confidently into the room to greet your 84-year-old female patient.
2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”
3. Extend your clenched fist toward her chest and wait for her to reciprocate.
4. Smile awkwardly behind your mask while you wait.
5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.
6. Wait.
7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.
8. Wait a bit more.
9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.
10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.
It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.
There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.
Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.
The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).
With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]
Systemic JIA and AOSD are the same disease, EULAR says
Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) should be grouped into one disease, Still’s disease, according to new diagnosis and treatment recommendations presented at the annual European Congress of Rheumatology.
The recommendations, made in collaboration with EULAR and the Pediatric Rheumatology European Society, emphasized that the ultimate treatment target for Still’s disease should be drug-free remission in all patients and that macrophage activation syndrome (MAS) should be identified and treated as soon as possible.
The task force focused on MAS because despite effective, innovative therapies, “we continued to see MAS,” said presenter Bruno Fautrel, MD, Pitié-Salpêtrière University Hospital, Paris. “We have to be very concerned about this potential complication.”
Dr. Fautrel copresented the recommendations with Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology, Bambino Gesù Hospital, Rome.
Diagnosis
Dr. Fautrel noted that the cutoff age of 16 that differentiates sJIA and AOSD is “arbitrary.” There are some differences in age: The frequency of the disease is higher in young children, but it plateaus in young adults. Children under 18 months old are also far more likely to develop MAS.
To diagnose and treat Still’s disease, the recommendations state that clinicians should consider four criteria:
- A fever spiking at or above 39° C (102.2° F) for at least 7 days.
- A transient rash, preferentially on the trunk, that coincides with fever spikes, rash is typically erythematous but other rashes, like urticaria, can be consistent with the diagnosis.
- Some musculoskeletal involvement is common, involving arthralgia/myalgia.
- High levels of inflammation identified by neutrophilic leukocytosis, increased serum C-reactive protein (CRP), and ferritin.
Dr. Fautrel noted that, while arthritis can be present, it is not necessary to make a diagnosis. In pediatrics, “arthritis is likely to happen after a few weeks of the evolution of the disease,” and waiting for arthritis to develop can lead to diagnostic delay, “which is a problem.”
For individuals with suspected Still’s disease, NSAIDs can be used as a “bridging therapy” before the diagnosis is confirmed.
Treatment
The recommendations emphasized that treatment and therapeutic strategy “should be based on shared decision-making between the parents/patients and the treating team,” with the ultimate goal of drug-free remission.
To achieve this goal, the document outlines time-based targets for clinically inactive disease (CID). At 4 weeks, patients should have no fever, reduction of active or swollen joint count by more than 50%, a normal CRP level, and a rating of less than 20 on a visual analog scale of 0-100. At 3 months, patients should maintain clinically inactive disease with a glucocorticoid dose of less than 0.1 or 0.2 mg/kg per day. At 6 months, CID should be maintained without glucocorticoids.
While the authors of the recommendations noted that glucocorticoids are efficacious, their long-term use should be avoided because of safety issues. An interleukin-1 or IL-6 inhibitor should be prioritized and initiated as soon as possible after diagnosis.
Patients should maintain CID between 3 and 6 months before tapering off biologics.
The recommendations are congruent with the 2021 American College of Rheumatology’s guidelines for sJIA, noted Karen Onel, MD, pediatric rheumatologist, Hospital for Special Surgery, New York, and the principle investigator for the ACR guidelines. One main difference is that the EULAR recommendations included time lines for treatment targets, while the ACR’s did not.
“It’s great to have these time lines in there,” she said in an interview, though there are still some unknowns. “We don’t actually know what the tapering frequency should be,” she said, “but these are definitely goals that we need to explore and see how they evolve.”
MAS and lung complications
The EULAR recommendations also touched on two concerning complications, particularly in children: MAS and lung disease. According to the document, MAS should be considered in patients with Still’s disease with these symptoms: fever, splenomegaly, elevated serum ferritin, low cell counts, abnormal liver function tests, elevated serum triglycerides, and intravascular activation of coagulation. The MAS 2016 criteria can also be used to facilitate diagnosis.
“MAS treatment must include high-dose glucocorticoids,” the document states. “In addition, treatments including anakinra, ciclosporin, and/or interferon-gamma inhibitors should be considered as a part of initial therapy.”
The recommendations also addressed the risk for lung disease, “which is an emerging issue, particularly in children, that the physician should be very well aware of,” Dr. De Benedetti said. This complication can arise at any time point of the disease, he added.
The document advised actively screening for lung disease by searching for clinical symptoms such as digital clubbing, persistent cough, and shortness of breath. Pulmonary function tests like pulse oximetry and diffusing capacity of the lungs for carbon monoxide may also be used, but these standard lung function tests are very difficult to do in children under 6 years old, Dr. De Benedetti noted. The recommendations advise performing high-resolution CT in “any patients with clinical concerns.”
“We have lowered the threshold for CT scan because of the emerging features of this lung disease that may actually be lethal and therefore require prompt attention,” Dr. De Benedetti noted.
The recommendations for lung disease are “broad,” as there is still much to learn about the risk for lung disease in a small portion of sJIA patients, Dr. Onel said.
“There’s a lot that we are trying to work out about this; exactly how to screen, who to screen, what to do, who to treat, and how to treat really remains unclear,” she said. “We absolutely agree that this is a major, major issue that we need to come to some sort of agreement upon, but we’re just not there yet.”
Dr. De Benedetti, Dr. Fautrel, and Dr. Onel disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) should be grouped into one disease, Still’s disease, according to new diagnosis and treatment recommendations presented at the annual European Congress of Rheumatology.
The recommendations, made in collaboration with EULAR and the Pediatric Rheumatology European Society, emphasized that the ultimate treatment target for Still’s disease should be drug-free remission in all patients and that macrophage activation syndrome (MAS) should be identified and treated as soon as possible.
The task force focused on MAS because despite effective, innovative therapies, “we continued to see MAS,” said presenter Bruno Fautrel, MD, Pitié-Salpêtrière University Hospital, Paris. “We have to be very concerned about this potential complication.”
Dr. Fautrel copresented the recommendations with Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology, Bambino Gesù Hospital, Rome.
Diagnosis
Dr. Fautrel noted that the cutoff age of 16 that differentiates sJIA and AOSD is “arbitrary.” There are some differences in age: The frequency of the disease is higher in young children, but it plateaus in young adults. Children under 18 months old are also far more likely to develop MAS.
To diagnose and treat Still’s disease, the recommendations state that clinicians should consider four criteria:
- A fever spiking at or above 39° C (102.2° F) for at least 7 days.
- A transient rash, preferentially on the trunk, that coincides with fever spikes, rash is typically erythematous but other rashes, like urticaria, can be consistent with the diagnosis.
- Some musculoskeletal involvement is common, involving arthralgia/myalgia.
- High levels of inflammation identified by neutrophilic leukocytosis, increased serum C-reactive protein (CRP), and ferritin.
Dr. Fautrel noted that, while arthritis can be present, it is not necessary to make a diagnosis. In pediatrics, “arthritis is likely to happen after a few weeks of the evolution of the disease,” and waiting for arthritis to develop can lead to diagnostic delay, “which is a problem.”
For individuals with suspected Still’s disease, NSAIDs can be used as a “bridging therapy” before the diagnosis is confirmed.
Treatment
The recommendations emphasized that treatment and therapeutic strategy “should be based on shared decision-making between the parents/patients and the treating team,” with the ultimate goal of drug-free remission.
To achieve this goal, the document outlines time-based targets for clinically inactive disease (CID). At 4 weeks, patients should have no fever, reduction of active or swollen joint count by more than 50%, a normal CRP level, and a rating of less than 20 on a visual analog scale of 0-100. At 3 months, patients should maintain clinically inactive disease with a glucocorticoid dose of less than 0.1 or 0.2 mg/kg per day. At 6 months, CID should be maintained without glucocorticoids.
While the authors of the recommendations noted that glucocorticoids are efficacious, their long-term use should be avoided because of safety issues. An interleukin-1 or IL-6 inhibitor should be prioritized and initiated as soon as possible after diagnosis.
Patients should maintain CID between 3 and 6 months before tapering off biologics.
The recommendations are congruent with the 2021 American College of Rheumatology’s guidelines for sJIA, noted Karen Onel, MD, pediatric rheumatologist, Hospital for Special Surgery, New York, and the principle investigator for the ACR guidelines. One main difference is that the EULAR recommendations included time lines for treatment targets, while the ACR’s did not.
“It’s great to have these time lines in there,” she said in an interview, though there are still some unknowns. “We don’t actually know what the tapering frequency should be,” she said, “but these are definitely goals that we need to explore and see how they evolve.”
MAS and lung complications
The EULAR recommendations also touched on two concerning complications, particularly in children: MAS and lung disease. According to the document, MAS should be considered in patients with Still’s disease with these symptoms: fever, splenomegaly, elevated serum ferritin, low cell counts, abnormal liver function tests, elevated serum triglycerides, and intravascular activation of coagulation. The MAS 2016 criteria can also be used to facilitate diagnosis.
“MAS treatment must include high-dose glucocorticoids,” the document states. “In addition, treatments including anakinra, ciclosporin, and/or interferon-gamma inhibitors should be considered as a part of initial therapy.”
The recommendations also addressed the risk for lung disease, “which is an emerging issue, particularly in children, that the physician should be very well aware of,” Dr. De Benedetti said. This complication can arise at any time point of the disease, he added.
The document advised actively screening for lung disease by searching for clinical symptoms such as digital clubbing, persistent cough, and shortness of breath. Pulmonary function tests like pulse oximetry and diffusing capacity of the lungs for carbon monoxide may also be used, but these standard lung function tests are very difficult to do in children under 6 years old, Dr. De Benedetti noted. The recommendations advise performing high-resolution CT in “any patients with clinical concerns.”
“We have lowered the threshold for CT scan because of the emerging features of this lung disease that may actually be lethal and therefore require prompt attention,” Dr. De Benedetti noted.
The recommendations for lung disease are “broad,” as there is still much to learn about the risk for lung disease in a small portion of sJIA patients, Dr. Onel said.
“There’s a lot that we are trying to work out about this; exactly how to screen, who to screen, what to do, who to treat, and how to treat really remains unclear,” she said. “We absolutely agree that this is a major, major issue that we need to come to some sort of agreement upon, but we’re just not there yet.”
Dr. De Benedetti, Dr. Fautrel, and Dr. Onel disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) should be grouped into one disease, Still’s disease, according to new diagnosis and treatment recommendations presented at the annual European Congress of Rheumatology.
The recommendations, made in collaboration with EULAR and the Pediatric Rheumatology European Society, emphasized that the ultimate treatment target for Still’s disease should be drug-free remission in all patients and that macrophage activation syndrome (MAS) should be identified and treated as soon as possible.
The task force focused on MAS because despite effective, innovative therapies, “we continued to see MAS,” said presenter Bruno Fautrel, MD, Pitié-Salpêtrière University Hospital, Paris. “We have to be very concerned about this potential complication.”
Dr. Fautrel copresented the recommendations with Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology, Bambino Gesù Hospital, Rome.
Diagnosis
Dr. Fautrel noted that the cutoff age of 16 that differentiates sJIA and AOSD is “arbitrary.” There are some differences in age: The frequency of the disease is higher in young children, but it plateaus in young adults. Children under 18 months old are also far more likely to develop MAS.
To diagnose and treat Still’s disease, the recommendations state that clinicians should consider four criteria:
- A fever spiking at or above 39° C (102.2° F) for at least 7 days.
- A transient rash, preferentially on the trunk, that coincides with fever spikes, rash is typically erythematous but other rashes, like urticaria, can be consistent with the diagnosis.
- Some musculoskeletal involvement is common, involving arthralgia/myalgia.
- High levels of inflammation identified by neutrophilic leukocytosis, increased serum C-reactive protein (CRP), and ferritin.
Dr. Fautrel noted that, while arthritis can be present, it is not necessary to make a diagnosis. In pediatrics, “arthritis is likely to happen after a few weeks of the evolution of the disease,” and waiting for arthritis to develop can lead to diagnostic delay, “which is a problem.”
For individuals with suspected Still’s disease, NSAIDs can be used as a “bridging therapy” before the diagnosis is confirmed.
Treatment
The recommendations emphasized that treatment and therapeutic strategy “should be based on shared decision-making between the parents/patients and the treating team,” with the ultimate goal of drug-free remission.
To achieve this goal, the document outlines time-based targets for clinically inactive disease (CID). At 4 weeks, patients should have no fever, reduction of active or swollen joint count by more than 50%, a normal CRP level, and a rating of less than 20 on a visual analog scale of 0-100. At 3 months, patients should maintain clinically inactive disease with a glucocorticoid dose of less than 0.1 or 0.2 mg/kg per day. At 6 months, CID should be maintained without glucocorticoids.
While the authors of the recommendations noted that glucocorticoids are efficacious, their long-term use should be avoided because of safety issues. An interleukin-1 or IL-6 inhibitor should be prioritized and initiated as soon as possible after diagnosis.
Patients should maintain CID between 3 and 6 months before tapering off biologics.
The recommendations are congruent with the 2021 American College of Rheumatology’s guidelines for sJIA, noted Karen Onel, MD, pediatric rheumatologist, Hospital for Special Surgery, New York, and the principle investigator for the ACR guidelines. One main difference is that the EULAR recommendations included time lines for treatment targets, while the ACR’s did not.
“It’s great to have these time lines in there,” she said in an interview, though there are still some unknowns. “We don’t actually know what the tapering frequency should be,” she said, “but these are definitely goals that we need to explore and see how they evolve.”
MAS and lung complications
The EULAR recommendations also touched on two concerning complications, particularly in children: MAS and lung disease. According to the document, MAS should be considered in patients with Still’s disease with these symptoms: fever, splenomegaly, elevated serum ferritin, low cell counts, abnormal liver function tests, elevated serum triglycerides, and intravascular activation of coagulation. The MAS 2016 criteria can also be used to facilitate diagnosis.
“MAS treatment must include high-dose glucocorticoids,” the document states. “In addition, treatments including anakinra, ciclosporin, and/or interferon-gamma inhibitors should be considered as a part of initial therapy.”
The recommendations also addressed the risk for lung disease, “which is an emerging issue, particularly in children, that the physician should be very well aware of,” Dr. De Benedetti said. This complication can arise at any time point of the disease, he added.
The document advised actively screening for lung disease by searching for clinical symptoms such as digital clubbing, persistent cough, and shortness of breath. Pulmonary function tests like pulse oximetry and diffusing capacity of the lungs for carbon monoxide may also be used, but these standard lung function tests are very difficult to do in children under 6 years old, Dr. De Benedetti noted. The recommendations advise performing high-resolution CT in “any patients with clinical concerns.”
“We have lowered the threshold for CT scan because of the emerging features of this lung disease that may actually be lethal and therefore require prompt attention,” Dr. De Benedetti noted.
The recommendations for lung disease are “broad,” as there is still much to learn about the risk for lung disease in a small portion of sJIA patients, Dr. Onel said.
“There’s a lot that we are trying to work out about this; exactly how to screen, who to screen, what to do, who to treat, and how to treat really remains unclear,” she said. “We absolutely agree that this is a major, major issue that we need to come to some sort of agreement upon, but we’re just not there yet.”
Dr. De Benedetti, Dr. Fautrel, and Dr. Onel disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EULAR 2023
Should you have a chaperone in the exam room? Many say yes
This transcript has been edited for clarity.
I’m Art Caplan, PhD. I’m at the division of medical ethics at NYU’s Grossman School of Medicine.
, such as breasts, genitalia, and the perianal area.
In some institutions, there has been a movement toward saying a chaperone must be present, that it’s mandatory. I know that is true at Yale’s health care centers and clinics. Others do so when the patient requests it. An interesting situation sometimes occurs when the hospital or the clinic requires a chaperone but the patient says, “I don’t want a chaperone. I want my privacy. I want the gynecologist or the urologist only. I don’t want anyone else to be seeing me. I’m not comfortable with anyone other than the doctor in the room.”
Complicating this issue of when is a chaperone appropriate and when can it be refused, if ever, is the fact that the role of chaperone is ill defined. For example, there isn’t really agreement on who can be a chaperone. Could it be a medical student? Could it be a nurse? Could it be another doctor? Should it be someone who at least has finished nursing school or medical school? Can it be a patient representative? There are no standards about who can play the role.
Should the chaperone be available to be seen when they’re in the room? Should they stay behind a curtain or somewhere where they’re not, so to speak, intrusive into what’s going on in the exam room? Do they sit in a chair? Do they stand? How do they behave, if you will? There’s no agreement.
There’s still no agreement on the training that a chaperone should have. Do we charge them with trying to represent what’s going on with the patient or trying to protect the doctor against any accusations that are ill founded about inappropriate conduct? Are they supposed to do both? How do they obtain consent, if they do, from the patient undergoing an examination in a sensitive part of their body or one that they’re sensitive about?
This area really requires some hard thinking if you’re considering having chaperones present. I think there are some online courses that offer some training. I haven’t looked at them, but they might be worth a look to see if they make you more comfortable about getting a chaperone oriented. I think it’s probably important to set a policy saying a chaperone must always be present for these kinds of examinations and list them, or one can be requested no matter what is going on in terms of the kind of exam being conducted.
There needs to be some statement saying that you have permission to either accept them or refuse them – or you don’t. Should they always be present, for example, with patients who are minors, adolescents or children? Does that extend that far out where a guardian, parent, or someone has to give permission?
In this area, I think we can all understand why chaperones have come to the fore, including allegations of misconduct and inappropriate touching, and considering comfort levels of patients to just put them more at ease. It’s obvious that we haven’t, as a nation or a medical profession, thought it through to the degree to which we have to.
I’m certainly not anti-chaperone, and I believe that if patients are more comfortable having one present, or a doctor is more comfortable having one present, or if we all agree that there are certain patients – kids – where certain types of examinations require or ought to expect the chaperone to be present, that’s wonderful.
We’ve got to lay out the rights of the doctors. We’ve got to lay out the rights of the institutions. We’ve got to lay out the rights of the patients. We should agree on who these people are. We should agree on how they’re trained.
We’ve got some work ahead of us if we’re going to have chaperones become a standard part of the medical examination.
Dr. Kaplan reported conflicts of interest with the Franklin Institute, Tengion, Biogen Idec, Johnson & Johnson, and PriCara.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Art Caplan, PhD. I’m at the division of medical ethics at NYU’s Grossman School of Medicine.
, such as breasts, genitalia, and the perianal area.
In some institutions, there has been a movement toward saying a chaperone must be present, that it’s mandatory. I know that is true at Yale’s health care centers and clinics. Others do so when the patient requests it. An interesting situation sometimes occurs when the hospital or the clinic requires a chaperone but the patient says, “I don’t want a chaperone. I want my privacy. I want the gynecologist or the urologist only. I don’t want anyone else to be seeing me. I’m not comfortable with anyone other than the doctor in the room.”
Complicating this issue of when is a chaperone appropriate and when can it be refused, if ever, is the fact that the role of chaperone is ill defined. For example, there isn’t really agreement on who can be a chaperone. Could it be a medical student? Could it be a nurse? Could it be another doctor? Should it be someone who at least has finished nursing school or medical school? Can it be a patient representative? There are no standards about who can play the role.
Should the chaperone be available to be seen when they’re in the room? Should they stay behind a curtain or somewhere where they’re not, so to speak, intrusive into what’s going on in the exam room? Do they sit in a chair? Do they stand? How do they behave, if you will? There’s no agreement.
There’s still no agreement on the training that a chaperone should have. Do we charge them with trying to represent what’s going on with the patient or trying to protect the doctor against any accusations that are ill founded about inappropriate conduct? Are they supposed to do both? How do they obtain consent, if they do, from the patient undergoing an examination in a sensitive part of their body or one that they’re sensitive about?
This area really requires some hard thinking if you’re considering having chaperones present. I think there are some online courses that offer some training. I haven’t looked at them, but they might be worth a look to see if they make you more comfortable about getting a chaperone oriented. I think it’s probably important to set a policy saying a chaperone must always be present for these kinds of examinations and list them, or one can be requested no matter what is going on in terms of the kind of exam being conducted.
There needs to be some statement saying that you have permission to either accept them or refuse them – or you don’t. Should they always be present, for example, with patients who are minors, adolescents or children? Does that extend that far out where a guardian, parent, or someone has to give permission?
In this area, I think we can all understand why chaperones have come to the fore, including allegations of misconduct and inappropriate touching, and considering comfort levels of patients to just put them more at ease. It’s obvious that we haven’t, as a nation or a medical profession, thought it through to the degree to which we have to.
I’m certainly not anti-chaperone, and I believe that if patients are more comfortable having one present, or a doctor is more comfortable having one present, or if we all agree that there are certain patients – kids – where certain types of examinations require or ought to expect the chaperone to be present, that’s wonderful.
We’ve got to lay out the rights of the doctors. We’ve got to lay out the rights of the institutions. We’ve got to lay out the rights of the patients. We should agree on who these people are. We should agree on how they’re trained.
We’ve got some work ahead of us if we’re going to have chaperones become a standard part of the medical examination.
Dr. Kaplan reported conflicts of interest with the Franklin Institute, Tengion, Biogen Idec, Johnson & Johnson, and PriCara.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Art Caplan, PhD. I’m at the division of medical ethics at NYU’s Grossman School of Medicine.
, such as breasts, genitalia, and the perianal area.
In some institutions, there has been a movement toward saying a chaperone must be present, that it’s mandatory. I know that is true at Yale’s health care centers and clinics. Others do so when the patient requests it. An interesting situation sometimes occurs when the hospital or the clinic requires a chaperone but the patient says, “I don’t want a chaperone. I want my privacy. I want the gynecologist or the urologist only. I don’t want anyone else to be seeing me. I’m not comfortable with anyone other than the doctor in the room.”
Complicating this issue of when is a chaperone appropriate and when can it be refused, if ever, is the fact that the role of chaperone is ill defined. For example, there isn’t really agreement on who can be a chaperone. Could it be a medical student? Could it be a nurse? Could it be another doctor? Should it be someone who at least has finished nursing school or medical school? Can it be a patient representative? There are no standards about who can play the role.
Should the chaperone be available to be seen when they’re in the room? Should they stay behind a curtain or somewhere where they’re not, so to speak, intrusive into what’s going on in the exam room? Do they sit in a chair? Do they stand? How do they behave, if you will? There’s no agreement.
There’s still no agreement on the training that a chaperone should have. Do we charge them with trying to represent what’s going on with the patient or trying to protect the doctor against any accusations that are ill founded about inappropriate conduct? Are they supposed to do both? How do they obtain consent, if they do, from the patient undergoing an examination in a sensitive part of their body or one that they’re sensitive about?
This area really requires some hard thinking if you’re considering having chaperones present. I think there are some online courses that offer some training. I haven’t looked at them, but they might be worth a look to see if they make you more comfortable about getting a chaperone oriented. I think it’s probably important to set a policy saying a chaperone must always be present for these kinds of examinations and list them, or one can be requested no matter what is going on in terms of the kind of exam being conducted.
There needs to be some statement saying that you have permission to either accept them or refuse them – or you don’t. Should they always be present, for example, with patients who are minors, adolescents or children? Does that extend that far out where a guardian, parent, or someone has to give permission?
In this area, I think we can all understand why chaperones have come to the fore, including allegations of misconduct and inappropriate touching, and considering comfort levels of patients to just put them more at ease. It’s obvious that we haven’t, as a nation or a medical profession, thought it through to the degree to which we have to.
I’m certainly not anti-chaperone, and I believe that if patients are more comfortable having one present, or a doctor is more comfortable having one present, or if we all agree that there are certain patients – kids – where certain types of examinations require or ought to expect the chaperone to be present, that’s wonderful.
We’ve got to lay out the rights of the doctors. We’ve got to lay out the rights of the institutions. We’ve got to lay out the rights of the patients. We should agree on who these people are. We should agree on how they’re trained.
We’ve got some work ahead of us if we’re going to have chaperones become a standard part of the medical examination.
Dr. Kaplan reported conflicts of interest with the Franklin Institute, Tengion, Biogen Idec, Johnson & Johnson, and PriCara.
A version of this article first appeared on Medscape.com.
EULAR issues imaging recommendations for crystal-induced arthropathies
A European Alliance of Associations for Rheumatology task force has released new guidance on imaging of crystal-induced arthropathies (CiA). The document provides recommendations for using imaging for diagnosis and monitoring of these types of diseases.
“These are the first-ever EULAR recommendations on imaging in this group of diseases. In fact, we are not aware of any similar international recommendations which provide guidance on which imaging technique, when, and how [they] should be used for crystal-induced arthropathies,” lead author Peter Mandl, MD, PhD, of the division of rheumatology at the Medical University of Vienna, told this news organization. Dr. Mandl presented the new recommendations at the annual European Congress of Rheumatology.
While some rheumatologists very familiar with crystal-induced arthropathies already regularly use imaging with these patients, these formal recommendations could highlight to wider audiences that “these imaging modalities can be very sensitive and specific for CiA,” said Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital in Boston. She was not involved with the work.
The document included general recommendations for imaging in CiA as well as specific recommendations for gout, basic calcium phosphate deposition disease (BCPD), and calcium pyrophosphate deposition disease (CPPD). Across all disease types, performing imaging on symptomatic areas as well as disease-specific target sites should be considered, the recommendations state. This includes the first metatarsophalangeal joint in gout, the wrist and knee in CPPD, and the shoulder in BCPD.
Both ultrasound (US) and dual-energy CT (DECT) are the recommended imaging modalities in gout. If imaging reveals characteristic features of monosodium urate (MSU) crystal deposition, synovial fluid analysis is not necessary to confirm a gout diagnosis. The volume of MSU crystals on imaging can also be used to predict future disease flares.
Showing imaging and explaining imaging findings may help patients understand their condition and adhere to treatment regimens, the recommendations state. “I think it’s a very powerful way to counsel patients,” Dr. Tedeschi said in an interview.
Imaging is necessary in the diagnosis of BCPD, and clinicians should use either conventional radiography or US. These imagining modalities are recommended for CPPD, and clinicians can use CT if they suspect axial involvement. The document does not recommend serial imaging for either BCPD or CPPD unless there has been an “unsuspected change in clinical characteristics.”
These recommendations highlight how imaging can have a “powerful impact on patient counseling and diagnosis,” said Dr. Tedeschi. She emphasized the importance of US training in rheumatology fellowship programs.
During his presentation at EULAR 2023, Dr. Mandl also highlighted a robust research agenda to further investigate how imaging can aid in the diagnosis and treatment of CiA. “It would be great to have an imaging modality someday that would help us differentiate between various types of calcium crystal,” he said.
Dr. Mandl has financial relationships with AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Roche, and UCB. Dr. Tedeschi has worked as a consultant for Novartis.
A version of this article first appeared on Medscape.com.
A European Alliance of Associations for Rheumatology task force has released new guidance on imaging of crystal-induced arthropathies (CiA). The document provides recommendations for using imaging for diagnosis and monitoring of these types of diseases.
“These are the first-ever EULAR recommendations on imaging in this group of diseases. In fact, we are not aware of any similar international recommendations which provide guidance on which imaging technique, when, and how [they] should be used for crystal-induced arthropathies,” lead author Peter Mandl, MD, PhD, of the division of rheumatology at the Medical University of Vienna, told this news organization. Dr. Mandl presented the new recommendations at the annual European Congress of Rheumatology.
While some rheumatologists very familiar with crystal-induced arthropathies already regularly use imaging with these patients, these formal recommendations could highlight to wider audiences that “these imaging modalities can be very sensitive and specific for CiA,” said Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital in Boston. She was not involved with the work.
The document included general recommendations for imaging in CiA as well as specific recommendations for gout, basic calcium phosphate deposition disease (BCPD), and calcium pyrophosphate deposition disease (CPPD). Across all disease types, performing imaging on symptomatic areas as well as disease-specific target sites should be considered, the recommendations state. This includes the first metatarsophalangeal joint in gout, the wrist and knee in CPPD, and the shoulder in BCPD.
Both ultrasound (US) and dual-energy CT (DECT) are the recommended imaging modalities in gout. If imaging reveals characteristic features of monosodium urate (MSU) crystal deposition, synovial fluid analysis is not necessary to confirm a gout diagnosis. The volume of MSU crystals on imaging can also be used to predict future disease flares.
Showing imaging and explaining imaging findings may help patients understand their condition and adhere to treatment regimens, the recommendations state. “I think it’s a very powerful way to counsel patients,” Dr. Tedeschi said in an interview.
Imaging is necessary in the diagnosis of BCPD, and clinicians should use either conventional radiography or US. These imagining modalities are recommended for CPPD, and clinicians can use CT if they suspect axial involvement. The document does not recommend serial imaging for either BCPD or CPPD unless there has been an “unsuspected change in clinical characteristics.”
These recommendations highlight how imaging can have a “powerful impact on patient counseling and diagnosis,” said Dr. Tedeschi. She emphasized the importance of US training in rheumatology fellowship programs.
During his presentation at EULAR 2023, Dr. Mandl also highlighted a robust research agenda to further investigate how imaging can aid in the diagnosis and treatment of CiA. “It would be great to have an imaging modality someday that would help us differentiate between various types of calcium crystal,” he said.
Dr. Mandl has financial relationships with AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Roche, and UCB. Dr. Tedeschi has worked as a consultant for Novartis.
A version of this article first appeared on Medscape.com.
A European Alliance of Associations for Rheumatology task force has released new guidance on imaging of crystal-induced arthropathies (CiA). The document provides recommendations for using imaging for diagnosis and monitoring of these types of diseases.
“These are the first-ever EULAR recommendations on imaging in this group of diseases. In fact, we are not aware of any similar international recommendations which provide guidance on which imaging technique, when, and how [they] should be used for crystal-induced arthropathies,” lead author Peter Mandl, MD, PhD, of the division of rheumatology at the Medical University of Vienna, told this news organization. Dr. Mandl presented the new recommendations at the annual European Congress of Rheumatology.
While some rheumatologists very familiar with crystal-induced arthropathies already regularly use imaging with these patients, these formal recommendations could highlight to wider audiences that “these imaging modalities can be very sensitive and specific for CiA,” said Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital in Boston. She was not involved with the work.
The document included general recommendations for imaging in CiA as well as specific recommendations for gout, basic calcium phosphate deposition disease (BCPD), and calcium pyrophosphate deposition disease (CPPD). Across all disease types, performing imaging on symptomatic areas as well as disease-specific target sites should be considered, the recommendations state. This includes the first metatarsophalangeal joint in gout, the wrist and knee in CPPD, and the shoulder in BCPD.
Both ultrasound (US) and dual-energy CT (DECT) are the recommended imaging modalities in gout. If imaging reveals characteristic features of monosodium urate (MSU) crystal deposition, synovial fluid analysis is not necessary to confirm a gout diagnosis. The volume of MSU crystals on imaging can also be used to predict future disease flares.
Showing imaging and explaining imaging findings may help patients understand their condition and adhere to treatment regimens, the recommendations state. “I think it’s a very powerful way to counsel patients,” Dr. Tedeschi said in an interview.
Imaging is necessary in the diagnosis of BCPD, and clinicians should use either conventional radiography or US. These imagining modalities are recommended for CPPD, and clinicians can use CT if they suspect axial involvement. The document does not recommend serial imaging for either BCPD or CPPD unless there has been an “unsuspected change in clinical characteristics.”
These recommendations highlight how imaging can have a “powerful impact on patient counseling and diagnosis,” said Dr. Tedeschi. She emphasized the importance of US training in rheumatology fellowship programs.
During his presentation at EULAR 2023, Dr. Mandl also highlighted a robust research agenda to further investigate how imaging can aid in the diagnosis and treatment of CiA. “It would be great to have an imaging modality someday that would help us differentiate between various types of calcium crystal,” he said.
Dr. Mandl has financial relationships with AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Roche, and UCB. Dr. Tedeschi has worked as a consultant for Novartis.
A version of this article first appeared on Medscape.com.
FROM EULAR 2023
Mucosal exposure device boosts AI-assisted detection of adenomas
based on results of a randomized trial.
Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.
“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”
To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).
The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.
“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”
The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.
The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.
The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.
Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.
Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.
The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.
Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.
Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.
The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.
Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.
Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.
based on results of a randomized trial.
Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.
“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”
To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).
The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.
“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”
The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.
The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.
based on results of a randomized trial.
Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.
“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”
To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).
The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.
“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”
The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.
The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.
FROM GASTROENTEROLOGY
Migraine clusters emerge from machine-learning analysis
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
FROM AHS 2023
Methotrexate does not impair sperm quality, small study finds
TOPLINE:
Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.
METHODOLOGY:
- Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
- Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
- Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
- Researchers tested samples in both groups for markers of testicular toxicity.
- Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.
TAKEAWAY:
- Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
- The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.
IN PRACTICE:
“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.
STUDY DETAILS:
Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.
LIMITATIONS:
The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.
DISCLOSURES:
Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.
METHODOLOGY:
- Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
- Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
- Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
- Researchers tested samples in both groups for markers of testicular toxicity.
- Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.
TAKEAWAY:
- Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
- The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.
IN PRACTICE:
“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.
STUDY DETAILS:
Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.
LIMITATIONS:
The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.
DISCLOSURES:
Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.
METHODOLOGY:
- Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
- Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
- Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
- Researchers tested samples in both groups for markers of testicular toxicity.
- Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.
TAKEAWAY:
- Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
- The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.
IN PRACTICE:
“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.
STUDY DETAILS:
Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.
LIMITATIONS:
The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.
DISCLOSURES:
Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.
A version of this article first appeared on Medscape.com.
New tool uses nanotechnology to speed up diagnostic testing of infectious disease
A new tool promises to expedite detection of infectious disease, according to researchers from McGill University, Montreal.
The diagnostic platform, called The device was tested for several respiratory viruses and bacteria, including the H1N1 influenza virus and SARS-CoV-2. It achieved 95% accuracy at identifying COVID-19 and its variants in 48 human saliva samples.
“COVID was something that opened our eyes, and now we have to think more seriously about point-of-care diagnostics,” Sara Mahshid, PhD, assistant professor of biomedical engineering and Canada Research Chair in Nano-Biosensing Devices at McGill University, said in an interview. The technology could become important for a range of medical applications, especially in low-resource areas.
The development was detailed in an article in Nature Nanotechnology.
Nonclinical setting
The COVID-19 pandemic has demonstrated the need for fast and accurate testing that can be used outside of a clinical setting. The gold-standard diagnostic method is PCR testing, but its accuracy comes with a trade-off. PCR testing involves a lengthy protocol and requires a centralized testing facility.
With QolorEX, the investigators aimed to develop a new test that achieves the accuracy of PCR in an automated tool that can be used outside of a testing facility or hospital setting. Dr. Mahshid noted a particular need for a tool that could be used in congregate settings, such as airports, schools, or restaurants.
The device is compact enough to sit on a tabletop or bench and can be used easily in group settings, according to Dr. Mahshid. In the future, she hopes to further miniaturize the device to make it more scalable for widespread use.
Requiring only a saliva sample, the tool is easy to use. Unlike current COVID-19 rapid tests, which involve several steps, the system is automated and does not require manually mixing reagents. After collecting a sample, a user taps a button in a smartphone or computer application. The device handles the rest.
“We’re not chemists who understand how to mix these solutions,” Dr. Mahshid said. Avoiding those extra steps may reduce the false positives and false negatives caused by user error.
Fast results
QolorEX can return results in 13 minutes, like a rapid antigen test does. Like a PCR test, the device uses nucleic acid amplification. But PCR tests typically take much longer. The sample analysis alone takes 1.5-2 hours.
The new test accelerates the reaction by injecting light-excited “hot” electrons from the surface of a nanoplasmonic sensor. The device then uses imaging and a machine learning algorithm to quantify a color transformation that occurs when a pathogen is present.
The fast, reliable results make the system potentially appropriate for use in places such as airports. Previously, passengers had to wait 24 hours for a negative COVID test before boarding a plane. A device such as QolorEX would allow screening on site.
The ability of the tool to distinguish between bacterial and viral infections so quickly is “an application that is both important and extremely difficult to achieve,” according to Nikhil Bhalla, PhD, in a research briefing. Dr. Bhalla is a lecturer in electronic engineering at Ulster University, Belfast, Ireland.
The researchers hope that by delivering results quickly, the device will help reduce the spread of respiratory diseases and possibly save lives.
‘Sensitive and specific’
The primary benefit of the tool is its ability to return results quickly while having low false positive and false negative rates, according to Leyla Soleymani, PhD, of McMaster University, Hamilton, Ont. “It is hard to come by rapid tests that are both sensitive and specific, compared to PCR,” Dr. Soleymani told this news organization.
Although QolorEX was developed to detect COVID-19 and other infectious diseases, the uses of the device are not limited to the pathogens tested. The tool can be applied to a range of tests that currently use PCR technology. Dr. Mahshid and her team are considering several other applications of the technology, such as analyzing therapeutics for antimicrobial-resistant pathogens prioritized by the World Health Organization. The technology may also have potential for detecting cancer and bacterial infections, Dr. Mahshid said in an interview.
But to Dr. Soleymani, the most exciting application remains its use in diagnosing infectious diseases. She noted, however, that it’s unclear whether the price of the device will be too high for widespread home use. It may be more practical for family physician clinics and other facilities.
Before the device becomes commercially available, more testing is needed to validate the results, which are based on a limited number of samples that were available in a research setting.
The study was supported by the MI4 Emergency COVID-19 Research Funding, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Canada Foundation for Innovation, and McGill University. Dr. Mahshid and Dr. Soleymani reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new tool promises to expedite detection of infectious disease, according to researchers from McGill University, Montreal.
The diagnostic platform, called The device was tested for several respiratory viruses and bacteria, including the H1N1 influenza virus and SARS-CoV-2. It achieved 95% accuracy at identifying COVID-19 and its variants in 48 human saliva samples.
“COVID was something that opened our eyes, and now we have to think more seriously about point-of-care diagnostics,” Sara Mahshid, PhD, assistant professor of biomedical engineering and Canada Research Chair in Nano-Biosensing Devices at McGill University, said in an interview. The technology could become important for a range of medical applications, especially in low-resource areas.
The development was detailed in an article in Nature Nanotechnology.
Nonclinical setting
The COVID-19 pandemic has demonstrated the need for fast and accurate testing that can be used outside of a clinical setting. The gold-standard diagnostic method is PCR testing, but its accuracy comes with a trade-off. PCR testing involves a lengthy protocol and requires a centralized testing facility.
With QolorEX, the investigators aimed to develop a new test that achieves the accuracy of PCR in an automated tool that can be used outside of a testing facility or hospital setting. Dr. Mahshid noted a particular need for a tool that could be used in congregate settings, such as airports, schools, or restaurants.
The device is compact enough to sit on a tabletop or bench and can be used easily in group settings, according to Dr. Mahshid. In the future, she hopes to further miniaturize the device to make it more scalable for widespread use.
Requiring only a saliva sample, the tool is easy to use. Unlike current COVID-19 rapid tests, which involve several steps, the system is automated and does not require manually mixing reagents. After collecting a sample, a user taps a button in a smartphone or computer application. The device handles the rest.
“We’re not chemists who understand how to mix these solutions,” Dr. Mahshid said. Avoiding those extra steps may reduce the false positives and false negatives caused by user error.
Fast results
QolorEX can return results in 13 minutes, like a rapid antigen test does. Like a PCR test, the device uses nucleic acid amplification. But PCR tests typically take much longer. The sample analysis alone takes 1.5-2 hours.
The new test accelerates the reaction by injecting light-excited “hot” electrons from the surface of a nanoplasmonic sensor. The device then uses imaging and a machine learning algorithm to quantify a color transformation that occurs when a pathogen is present.
The fast, reliable results make the system potentially appropriate for use in places such as airports. Previously, passengers had to wait 24 hours for a negative COVID test before boarding a plane. A device such as QolorEX would allow screening on site.
The ability of the tool to distinguish between bacterial and viral infections so quickly is “an application that is both important and extremely difficult to achieve,” according to Nikhil Bhalla, PhD, in a research briefing. Dr. Bhalla is a lecturer in electronic engineering at Ulster University, Belfast, Ireland.
The researchers hope that by delivering results quickly, the device will help reduce the spread of respiratory diseases and possibly save lives.
‘Sensitive and specific’
The primary benefit of the tool is its ability to return results quickly while having low false positive and false negative rates, according to Leyla Soleymani, PhD, of McMaster University, Hamilton, Ont. “It is hard to come by rapid tests that are both sensitive and specific, compared to PCR,” Dr. Soleymani told this news organization.
Although QolorEX was developed to detect COVID-19 and other infectious diseases, the uses of the device are not limited to the pathogens tested. The tool can be applied to a range of tests that currently use PCR technology. Dr. Mahshid and her team are considering several other applications of the technology, such as analyzing therapeutics for antimicrobial-resistant pathogens prioritized by the World Health Organization. The technology may also have potential for detecting cancer and bacterial infections, Dr. Mahshid said in an interview.
But to Dr. Soleymani, the most exciting application remains its use in diagnosing infectious diseases. She noted, however, that it’s unclear whether the price of the device will be too high for widespread home use. It may be more practical for family physician clinics and other facilities.
Before the device becomes commercially available, more testing is needed to validate the results, which are based on a limited number of samples that were available in a research setting.
The study was supported by the MI4 Emergency COVID-19 Research Funding, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Canada Foundation for Innovation, and McGill University. Dr. Mahshid and Dr. Soleymani reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new tool promises to expedite detection of infectious disease, according to researchers from McGill University, Montreal.
The diagnostic platform, called The device was tested for several respiratory viruses and bacteria, including the H1N1 influenza virus and SARS-CoV-2. It achieved 95% accuracy at identifying COVID-19 and its variants in 48 human saliva samples.
“COVID was something that opened our eyes, and now we have to think more seriously about point-of-care diagnostics,” Sara Mahshid, PhD, assistant professor of biomedical engineering and Canada Research Chair in Nano-Biosensing Devices at McGill University, said in an interview. The technology could become important for a range of medical applications, especially in low-resource areas.
The development was detailed in an article in Nature Nanotechnology.
Nonclinical setting
The COVID-19 pandemic has demonstrated the need for fast and accurate testing that can be used outside of a clinical setting. The gold-standard diagnostic method is PCR testing, but its accuracy comes with a trade-off. PCR testing involves a lengthy protocol and requires a centralized testing facility.
With QolorEX, the investigators aimed to develop a new test that achieves the accuracy of PCR in an automated tool that can be used outside of a testing facility or hospital setting. Dr. Mahshid noted a particular need for a tool that could be used in congregate settings, such as airports, schools, or restaurants.
The device is compact enough to sit on a tabletop or bench and can be used easily in group settings, according to Dr. Mahshid. In the future, she hopes to further miniaturize the device to make it more scalable for widespread use.
Requiring only a saliva sample, the tool is easy to use. Unlike current COVID-19 rapid tests, which involve several steps, the system is automated and does not require manually mixing reagents. After collecting a sample, a user taps a button in a smartphone or computer application. The device handles the rest.
“We’re not chemists who understand how to mix these solutions,” Dr. Mahshid said. Avoiding those extra steps may reduce the false positives and false negatives caused by user error.
Fast results
QolorEX can return results in 13 minutes, like a rapid antigen test does. Like a PCR test, the device uses nucleic acid amplification. But PCR tests typically take much longer. The sample analysis alone takes 1.5-2 hours.
The new test accelerates the reaction by injecting light-excited “hot” electrons from the surface of a nanoplasmonic sensor. The device then uses imaging and a machine learning algorithm to quantify a color transformation that occurs when a pathogen is present.
The fast, reliable results make the system potentially appropriate for use in places such as airports. Previously, passengers had to wait 24 hours for a negative COVID test before boarding a plane. A device such as QolorEX would allow screening on site.
The ability of the tool to distinguish between bacterial and viral infections so quickly is “an application that is both important and extremely difficult to achieve,” according to Nikhil Bhalla, PhD, in a research briefing. Dr. Bhalla is a lecturer in electronic engineering at Ulster University, Belfast, Ireland.
The researchers hope that by delivering results quickly, the device will help reduce the spread of respiratory diseases and possibly save lives.
‘Sensitive and specific’
The primary benefit of the tool is its ability to return results quickly while having low false positive and false negative rates, according to Leyla Soleymani, PhD, of McMaster University, Hamilton, Ont. “It is hard to come by rapid tests that are both sensitive and specific, compared to PCR,” Dr. Soleymani told this news organization.
Although QolorEX was developed to detect COVID-19 and other infectious diseases, the uses of the device are not limited to the pathogens tested. The tool can be applied to a range of tests that currently use PCR technology. Dr. Mahshid and her team are considering several other applications of the technology, such as analyzing therapeutics for antimicrobial-resistant pathogens prioritized by the World Health Organization. The technology may also have potential for detecting cancer and bacterial infections, Dr. Mahshid said in an interview.
But to Dr. Soleymani, the most exciting application remains its use in diagnosing infectious diseases. She noted, however, that it’s unclear whether the price of the device will be too high for widespread home use. It may be more practical for family physician clinics and other facilities.
Before the device becomes commercially available, more testing is needed to validate the results, which are based on a limited number of samples that were available in a research setting.
The study was supported by the MI4 Emergency COVID-19 Research Funding, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Canada Foundation for Innovation, and McGill University. Dr. Mahshid and Dr. Soleymani reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NATURE NANOTECHNOLOGY
Is education or screening better for type 1 diabetes?
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.