Federal Practitioner

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.

An interesting situation has arisen that many doctors who do physical examinations and primary care are facing, which is whether a chaperone has to be present for any examination of what are often referred to as sensitive areas, 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.

An interesting situation has arisen that many doctors who do physical examinations and primary care are facing, which is whether a chaperone has to be present for any examination of what are often referred to as sensitive areas, 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.

An interesting situation has arisen that many doctors who do physical examinations and primary care are facing, which is whether a chaperone has to be present for any examination of what are often referred to as sensitive areas, 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.

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.

AUSTIN, TEX. – A new machine-learning analysis of a large group of migraine patients has identified subgroups that share both clinical and therapeutic response traits. 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. – A new machine-learning analysis of a large group of migraine patients has identified subgroups that share both clinical and therapeutic response traits. 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. – A new machine-learning analysis of a large group of migraine patients has identified subgroups that share both clinical and therapeutic response traits. 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.
 

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.

A new tool promises to expedite detection of infectious disease, according to researchers from McGill University, Montreal.

The diagnostic platform, called QolorEX, was developed by investigators at the university by combining existing technologies to build a new tool for accurate pathogen detection in less than 15 minutes. 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 QolorEX, was developed by investigators at the university by combining existing technologies to build a new tool for accurate pathogen detection in less than 15 minutes. 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 QolorEX, was developed by investigators at the university by combining existing technologies to build a new tool for accurate pathogen detection in less than 15 minutes. 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.

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. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts 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. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts 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. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts 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.

Although we continue to hear a chorus of cautions from the wise folks in the public health community, most of us and our political leaders have allowed the SARS-CoV-2 pandemic to slip quietly into the dark recesses of our been-there-done-that pile. Obviously, this failure to continue learning from our mistakes is an oversight for which we will pay dearly the next time a public health crisis requiring a coordinated effort on a national and international scale raises its ugly head.

However, there is a significant portion of the population for whom the pandemic is fresh in their minds because they are experiencing the symptoms of what they have been told is long COVID. In January 2023 the Kaiser Family Foundation reported that 15% of the U.S. population feels that at some point they have experienced the symptoms of long COVID. And 6% report that they believe they currently have long COVID.

As long ago as February of 2021, Congress gave the National Institutes of Health $1.5 billion to fund a 4-year study of the prolonged health consequence of SARS-CoV-2. Sadly, 2 years into the study we aren’t too much further along in our search for answers. The Post Acute Sequelae of SARS-CoV-2 has earned an acronym, PASC, but it continues to be little more than a laundry list of vague symptoms including shortness of breath, fatigue, fever, headaches, “brain fog,” and a variety of other neurologic problems. We seem to have slipped into the same trap we find ourselves in with conditions such as chronic Lyme disease and chronic fatigue syndrome that lack workable diagnostic criteria.

However, I have just stumbled across a study in the JAMA Network Open that hints at a partial answer. Using data collected from a prospective study of nurses, investigators based at the T.H. Chan School of Public Health at Harvard found that adherence to healthy sleep prior to infection with COVID was inversely related to PCC, or Post COVID Condition, their chosen acronym for long COVID.

After taking into account a long list of covariants, the investigators found that women with consistently healthy sleep before and after their infection had the lowest risk of PCC when compared with women with consistently unhealthy sleep.

This finding seems to be telling us is that we shouldn’t be surprised to learn that folks who were relatively less healthy prior to contracting COVID are more likely to report feeling unhealthy after the acute phase of the illness has passed. It is unclear whether this observation is because their suboptimal health prior to the infection made them more vulnerable to its aftereffects or whether this is a return to their baseline for which we have labeled long COVID.

The results of this study are particularly important because it highlights our continued failure to acknowledge the critical role of sleep in the entire wellness picture. The broader message is of equal importance and that is when we are trying to discover what is making our patients sick, we must adhere to our traditional practice of taking a good and thorough history. When a patient asks the surgeon whether he will be able to play the violin after surgery, the prudent physician will always ask whether the patient has ever played the instrument.

As with any good study, it leaves more questions than it answers. While this study addresses the vague and neurologically based symptoms of long COVID, many of which are known symptoms associated with sleep deprivation, it doesn’t address the patients with more organically based symptoms such as those who have pulmonary or renal damage acquired during the acute phase of the illness. Many of these unfortunate individuals may have entered the pandemic with already damaged or vulnerable organ systems.

Finally, it leaves a very interesting question unanswered: Can we help the long COVID patients suffering with primarily neurologic symptoms by aggressively managing their preexisting unhealthy sleep habits? Or, has the damage already been done? I suspect and certainly hope it is the former.
 

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

Although we continue to hear a chorus of cautions from the wise folks in the public health community, most of us and our political leaders have allowed the SARS-CoV-2 pandemic to slip quietly into the dark recesses of our been-there-done-that pile. Obviously, this failure to continue learning from our mistakes is an oversight for which we will pay dearly the next time a public health crisis requiring a coordinated effort on a national and international scale raises its ugly head.

However, there is a significant portion of the population for whom the pandemic is fresh in their minds because they are experiencing the symptoms of what they have been told is long COVID. In January 2023 the Kaiser Family Foundation reported that 15% of the U.S. population feels that at some point they have experienced the symptoms of long COVID. And 6% report that they believe they currently have long COVID.

As long ago as February of 2021, Congress gave the National Institutes of Health $1.5 billion to fund a 4-year study of the prolonged health consequence of SARS-CoV-2. Sadly, 2 years into the study we aren’t too much further along in our search for answers. The Post Acute Sequelae of SARS-CoV-2 has earned an acronym, PASC, but it continues to be little more than a laundry list of vague symptoms including shortness of breath, fatigue, fever, headaches, “brain fog,” and a variety of other neurologic problems. We seem to have slipped into the same trap we find ourselves in with conditions such as chronic Lyme disease and chronic fatigue syndrome that lack workable diagnostic criteria.

However, I have just stumbled across a study in the JAMA Network Open that hints at a partial answer. Using data collected from a prospective study of nurses, investigators based at the T.H. Chan School of Public Health at Harvard found that adherence to healthy sleep prior to infection with COVID was inversely related to PCC, or Post COVID Condition, their chosen acronym for long COVID.

After taking into account a long list of covariants, the investigators found that women with consistently healthy sleep before and after their infection had the lowest risk of PCC when compared with women with consistently unhealthy sleep.

This finding seems to be telling us is that we shouldn’t be surprised to learn that folks who were relatively less healthy prior to contracting COVID are more likely to report feeling unhealthy after the acute phase of the illness has passed. It is unclear whether this observation is because their suboptimal health prior to the infection made them more vulnerable to its aftereffects or whether this is a return to their baseline for which we have labeled long COVID.

The results of this study are particularly important because it highlights our continued failure to acknowledge the critical role of sleep in the entire wellness picture. The broader message is of equal importance and that is when we are trying to discover what is making our patients sick, we must adhere to our traditional practice of taking a good and thorough history. When a patient asks the surgeon whether he will be able to play the violin after surgery, the prudent physician will always ask whether the patient has ever played the instrument.

As with any good study, it leaves more questions than it answers. While this study addresses the vague and neurologically based symptoms of long COVID, many of which are known symptoms associated with sleep deprivation, it doesn’t address the patients with more organically based symptoms such as those who have pulmonary or renal damage acquired during the acute phase of the illness. Many of these unfortunate individuals may have entered the pandemic with already damaged or vulnerable organ systems.

Finally, it leaves a very interesting question unanswered: Can we help the long COVID patients suffering with primarily neurologic symptoms by aggressively managing their preexisting unhealthy sleep habits? Or, has the damage already been done? I suspect and certainly hope it is the former.
 

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

Although we continue to hear a chorus of cautions from the wise folks in the public health community, most of us and our political leaders have allowed the SARS-CoV-2 pandemic to slip quietly into the dark recesses of our been-there-done-that pile. Obviously, this failure to continue learning from our mistakes is an oversight for which we will pay dearly the next time a public health crisis requiring a coordinated effort on a national and international scale raises its ugly head.

However, there is a significant portion of the population for whom the pandemic is fresh in their minds because they are experiencing the symptoms of what they have been told is long COVID. In January 2023 the Kaiser Family Foundation reported that 15% of the U.S. population feels that at some point they have experienced the symptoms of long COVID. And 6% report that they believe they currently have long COVID.

As long ago as February of 2021, Congress gave the National Institutes of Health $1.5 billion to fund a 4-year study of the prolonged health consequence of SARS-CoV-2. Sadly, 2 years into the study we aren’t too much further along in our search for answers. The Post Acute Sequelae of SARS-CoV-2 has earned an acronym, PASC, but it continues to be little more than a laundry list of vague symptoms including shortness of breath, fatigue, fever, headaches, “brain fog,” and a variety of other neurologic problems. We seem to have slipped into the same trap we find ourselves in with conditions such as chronic Lyme disease and chronic fatigue syndrome that lack workable diagnostic criteria.

However, I have just stumbled across a study in the JAMA Network Open that hints at a partial answer. Using data collected from a prospective study of nurses, investigators based at the T.H. Chan School of Public Health at Harvard found that adherence to healthy sleep prior to infection with COVID was inversely related to PCC, or Post COVID Condition, their chosen acronym for long COVID.

After taking into account a long list of covariants, the investigators found that women with consistently healthy sleep before and after their infection had the lowest risk of PCC when compared with women with consistently unhealthy sleep.

This finding seems to be telling us is that we shouldn’t be surprised to learn that folks who were relatively less healthy prior to contracting COVID are more likely to report feeling unhealthy after the acute phase of the illness has passed. It is unclear whether this observation is because their suboptimal health prior to the infection made them more vulnerable to its aftereffects or whether this is a return to their baseline for which we have labeled long COVID.

The results of this study are particularly important because it highlights our continued failure to acknowledge the critical role of sleep in the entire wellness picture. The broader message is of equal importance and that is when we are trying to discover what is making our patients sick, we must adhere to our traditional practice of taking a good and thorough history. When a patient asks the surgeon whether he will be able to play the violin after surgery, the prudent physician will always ask whether the patient has ever played the instrument.

As with any good study, it leaves more questions than it answers. While this study addresses the vague and neurologically based symptoms of long COVID, many of which are known symptoms associated with sleep deprivation, it doesn’t address the patients with more organically based symptoms such as those who have pulmonary or renal damage acquired during the acute phase of the illness. Many of these unfortunate individuals may have entered the pandemic with already damaged or vulnerable organ systems.

Finally, it leaves a very interesting question unanswered: Can we help the long COVID patients suffering with primarily neurologic symptoms by aggressively managing their preexisting unhealthy sleep habits? Or, has the damage already been done? I suspect and certainly hope it is the former.
 

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

WakeMed emergency department physician and medical director, Graham Snyder, MD, has seen his fair share of deaths: an average of one or two per day. That’s part of the job. Some of the deaths were the result of risky behavior, ongoing health problems, and other natural causes.

But what he didn’t find acceptable was losing a 6-year-old girl in a backyard pool drowning at what was meant to be a celebratory birthday party and family reunion.

“There were aunts and uncles and brothers and sisters and cousins, and the pool was packed, and they’re having a great time. One of the parents looked over and saw that she was swimming around underneath but acting weird. A relative pulled her up by the arm, and she was dead,” he said. “What nobody could tell me, and what they’ll live with the rest of their life, is how long was she under water?”

So Dr. Snyder invented a solution. The catch: He’s among an interesting set of doctors whose side gigs are solving critical problems affecting patients where they live. These are not medical devices for clinical use. They’re innovative products that everyday folks can use to make their lives safer and healthier. The goal: Improving systemic and “unsolvable” issues that harm society.

The cool part: Any MD with an idea can get in on the game.
 

Keeping little heads above water

Drowning is the leading cause of death in young children ages 1-4 years, and the second leading cause for children ages 5-14 years. The issue, Dr. Snyder explained, is not that rescuers couldn’t get to these children in time. “It’s that nobody knew to start looking.”

Dr. Snyder created a collar that alerts those around the swimmer that they are in trouble. The SEAL SwimSafe drowning prevention technology sets off an alarm system if a child is under water for too long. The necklace has been used to protect more than 10,000 children, including at larger swim facilities, such as the YMCA. 

When Dr. Snyder first started pursuing his invention, he asked himself two key questions: “Has someone already tried this? And if they did, why did they not succeed?” These questions help counteract the potential arrogance, he says, with imagining that you are the first person to have a certain idea. And using whatever reason others didn’t succeed as your “secret sauce” helps lead to more success. He also had to consider obstacles. People might resist wearing a collar or necklace while swimming or putting one on their child, like the reluctance around wearing bicycle helmets when they gained popularity in the 1980s. He concluded that the collars would work best at larger facilities, where they were mandated.

Another obstacle was false alarms. “It was possible to trigger a false alarm, and that could really scare people,” Dr. Snyder said. He is still considering systems to prevent the collars from being stolen or from “13-year-old boys hiding them in the water drain and making everyone really scared when an alarm is going off.”

The demand is real, however, and is based on alarming data. Safe Kids has reported that 66% of natural water drownings and around half of pool drownings happened with an adult supervising. They added, however, that supervision is often lacking or insufficient, such as a parent not being within arm’s reach of a young kid. As Dr. Snyder told reporters in a 2018 story, even the most well-intentioned parents still “miss something” sometimes, and this technology is for that moment.

“This is a completely solvable problem, but not a flip-a-switch, one and done,” he said, pointing to his product as a part of a more comprehensive approach, such as in Europe, where mandated public school swimming lessons are helping to decrease drowning deaths.

The pandemic slowed progress for the SEAL SwimSafe collar, which is currently waiting on a new funder or investor to take the reins. But the concept is alive and well with competitors pursuing related ideas. Dr. Snyder is holding out hope that entrepreneurs, scientists, public health workers, researchers, and others will be interested in continuing this work.
 

Eliminating the stigma of incontinence

Ever had an accident before making it to the bathroom? So have two-thirds of adult women, and almost one-third of older men. Incontinence is linked to a wide variety of conditions, from pelvic-floor trauma to neurological issues to diabetes, and others. Urologist Jessica Lubahn, MD, in Portland, Ore., saw one too many patients feeling this type of shame, unaware that the condition was so common. In addition, she personally experienced childbirth-related incontinence, and helped a relative who was having incontinence after prostate cancer surgery.

“He had a great result, but he had confided in me ... it was one of the only times in his life that he’s been truly depressed,” Dr. Lubahn said. “It’s not even the amount of leakage, but the smell, the stigma is so embarrassing, that not only is it an inconvenience, but [it affects] your entire psyche.” She thought there had to be a better solution than the “demeaning” act of wearing adult diapers.

Noting the explosion of the period panty industry in the past decade, Dr. Lubahn wanted to “destigmatize” incontinence in the same way menstruation education and products have been. She created ONDR incontinence underwear, specifically meant for urine, to ease the mental and physical burden on her patients and many others.

Dr. Lubahn said a process happens when you decide to start talking about the product you want to make rather than trying to find answers on your own. “A lot of people are so afraid to talk about their ideas because they’re afraid it’s going to get stolen or scooped, or it might fail,” she said. “I just openly discussed it, kind of like cocktail party conversation – ‘Wouldn’t it be funny if you just pee into your underwear?’ ” She noticed each connection led to finding more people to help her along her journey.

Dr. Lubahn studied the apparel industry, learning that overseas manufacturers were more helpful and cost-effective. She navigated issues such as a special stitch that prevented leakage and other details. She was also intent on using eco-friendly products that offset the environmental impact of pads, liners, and diapers. She said there’s a strong entrepreneurship community that can help other physician-inventors get grants, be part of accelerator programs, and receive support.

Six years after the original idea, Dr. Lubahn’s product was released in 2020. She now sells eight types of underwear for women and men’s boxer briefs. She wears them herself daily.
 

Deterring carjackers, saving lives

In 2022, carjackings tripled in Chicago and Memphis. The areas have the highest rates in 30 cities that the Council on Criminal Justice analyzed in a report on pandemic crime rates. According to the report, nearly 40% of offenders used a firearm, more than a quarter of victims were injured, and only around half of the vehicles taken were recovered. In addition, vehicles are sometimes used in secondary crimes, such as drive-by shootings. William Yates, MD, former trauma surgeon, now turned hair restoration surgeon in Chicago, saw the evidence of those crimes daily.

“I was perplexed by carjacking because there wasn’t any answer, and it just kept getting worse and worse. A lot of innocent people were being affected,” he said. “I was seeing deaths – needless. If you give them any push back at all, they will shoot you.”

As a deterrent to counter this “easy crime,” he invented the Yates Device, an alarm system designed to prevent or interrupt carjacking. The driver can activate a switch located beneath the foot pedal or an app on the phone to trigger a programmed high-decibel alarm. Critically, it allows the carjacker to drive a safe distance away from the victim before it starts going off.

The alarm “turns your car into a very noisy Christmas tree on a time delay,” Dr. Yates explained. An external siren blares “stolen vehicle” repeatedly. A camera records everything in the car. Lights flash. Only the original driver can turn off the system. Later, once the car is abandoned, the police can help recover the vehicle.

In Dr. Yates’ experience, the invention process takes longer than you think. He worked through earlier iterations with strobe lights, but these could lead to bystanders getting hurt if the carjacker couldn’t see, for example. Developing the final product and applying for patents was a two-part process.

“The first is part is a pending patent phase, which secures your place in line,” he said. “After 1 year, we filed the utility patent as the final documentation that the invention is truly unique. That has been in process for a year now and the attorneys say we should receive approval soon.”

The product has initially been tested in seven cars for about 1 year. Dr. Yates is measuring how the system performs in all types of weather, including Chicago’s below-zero temperatures. The product is not available to the public for purchase yet because Dr. Yates is still seeking funding to have it mass produced, but it is currently being evaluated by Korean automakers for their car manufacturers.

“Everybody was saying ‘Let’s do something about this,’ but I didn’t see anybody doing anything yet,” Dr. Yates recalled. In the surgeon’s lounge, everybody has ideas. “You go around the room, and every doctor would have five ideas that would make them the richest doctor, but nobody takes it beyond that stage – talk. You have to synthesize that into a plan, to take action.”

Dr. Yates said that many doctors have the intellect to invent, but they aren’t in a network like entrepreneurs to bring their ideas to life.

For Dr. Yates, it takes a curious mindset to solve these daunting problems. “I’m always curious, always looking for how to improve something, to get better outcomes you have to be asking questions and just never let it go.”
 

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

WakeMed emergency department physician and medical director, Graham Snyder, MD, has seen his fair share of deaths: an average of one or two per day. That’s part of the job. Some of the deaths were the result of risky behavior, ongoing health problems, and other natural causes.

But what he didn’t find acceptable was losing a 6-year-old girl in a backyard pool drowning at what was meant to be a celebratory birthday party and family reunion.

“There were aunts and uncles and brothers and sisters and cousins, and the pool was packed, and they’re having a great time. One of the parents looked over and saw that she was swimming around underneath but acting weird. A relative pulled her up by the arm, and she was dead,” he said. “What nobody could tell me, and what they’ll live with the rest of their life, is how long was she under water?”

So Dr. Snyder invented a solution. The catch: He’s among an interesting set of doctors whose side gigs are solving critical problems affecting patients where they live. These are not medical devices for clinical use. They’re innovative products that everyday folks can use to make their lives safer and healthier. The goal: Improving systemic and “unsolvable” issues that harm society.

The cool part: Any MD with an idea can get in on the game.
 

Keeping little heads above water

Drowning is the leading cause of death in young children ages 1-4 years, and the second leading cause for children ages 5-14 years. The issue, Dr. Snyder explained, is not that rescuers couldn’t get to these children in time. “It’s that nobody knew to start looking.”

Dr. Snyder created a collar that alerts those around the swimmer that they are in trouble. The SEAL SwimSafe drowning prevention technology sets off an alarm system if a child is under water for too long. The necklace has been used to protect more than 10,000 children, including at larger swim facilities, such as the YMCA. 

When Dr. Snyder first started pursuing his invention, he asked himself two key questions: “Has someone already tried this? And if they did, why did they not succeed?” These questions help counteract the potential arrogance, he says, with imagining that you are the first person to have a certain idea. And using whatever reason others didn’t succeed as your “secret sauce” helps lead to more success. He also had to consider obstacles. People might resist wearing a collar or necklace while swimming or putting one on their child, like the reluctance around wearing bicycle helmets when they gained popularity in the 1980s. He concluded that the collars would work best at larger facilities, where they were mandated.

Another obstacle was false alarms. “It was possible to trigger a false alarm, and that could really scare people,” Dr. Snyder said. He is still considering systems to prevent the collars from being stolen or from “13-year-old boys hiding them in the water drain and making everyone really scared when an alarm is going off.”

The demand is real, however, and is based on alarming data. Safe Kids has reported that 66% of natural water drownings and around half of pool drownings happened with an adult supervising. They added, however, that supervision is often lacking or insufficient, such as a parent not being within arm’s reach of a young kid. As Dr. Snyder told reporters in a 2018 story, even the most well-intentioned parents still “miss something” sometimes, and this technology is for that moment.

“This is a completely solvable problem, but not a flip-a-switch, one and done,” he said, pointing to his product as a part of a more comprehensive approach, such as in Europe, where mandated public school swimming lessons are helping to decrease drowning deaths.

The pandemic slowed progress for the SEAL SwimSafe collar, which is currently waiting on a new funder or investor to take the reins. But the concept is alive and well with competitors pursuing related ideas. Dr. Snyder is holding out hope that entrepreneurs, scientists, public health workers, researchers, and others will be interested in continuing this work.
 

Eliminating the stigma of incontinence

Ever had an accident before making it to the bathroom? So have two-thirds of adult women, and almost one-third of older men. Incontinence is linked to a wide variety of conditions, from pelvic-floor trauma to neurological issues to diabetes, and others. Urologist Jessica Lubahn, MD, in Portland, Ore., saw one too many patients feeling this type of shame, unaware that the condition was so common. In addition, she personally experienced childbirth-related incontinence, and helped a relative who was having incontinence after prostate cancer surgery.

“He had a great result, but he had confided in me ... it was one of the only times in his life that he’s been truly depressed,” Dr. Lubahn said. “It’s not even the amount of leakage, but the smell, the stigma is so embarrassing, that not only is it an inconvenience, but [it affects] your entire psyche.” She thought there had to be a better solution than the “demeaning” act of wearing adult diapers.

Noting the explosion of the period panty industry in the past decade, Dr. Lubahn wanted to “destigmatize” incontinence in the same way menstruation education and products have been. She created ONDR incontinence underwear, specifically meant for urine, to ease the mental and physical burden on her patients and many others.

Dr. Lubahn said a process happens when you decide to start talking about the product you want to make rather than trying to find answers on your own. “A lot of people are so afraid to talk about their ideas because they’re afraid it’s going to get stolen or scooped, or it might fail,” she said. “I just openly discussed it, kind of like cocktail party conversation – ‘Wouldn’t it be funny if you just pee into your underwear?’ ” She noticed each connection led to finding more people to help her along her journey.

Dr. Lubahn studied the apparel industry, learning that overseas manufacturers were more helpful and cost-effective. She navigated issues such as a special stitch that prevented leakage and other details. She was also intent on using eco-friendly products that offset the environmental impact of pads, liners, and diapers. She said there’s a strong entrepreneurship community that can help other physician-inventors get grants, be part of accelerator programs, and receive support.

Six years after the original idea, Dr. Lubahn’s product was released in 2020. She now sells eight types of underwear for women and men’s boxer briefs. She wears them herself daily.
 

Deterring carjackers, saving lives

In 2022, carjackings tripled in Chicago and Memphis. The areas have the highest rates in 30 cities that the Council on Criminal Justice analyzed in a report on pandemic crime rates. According to the report, nearly 40% of offenders used a firearm, more than a quarter of victims were injured, and only around half of the vehicles taken were recovered. In addition, vehicles are sometimes used in secondary crimes, such as drive-by shootings. William Yates, MD, former trauma surgeon, now turned hair restoration surgeon in Chicago, saw the evidence of those crimes daily.

“I was perplexed by carjacking because there wasn’t any answer, and it just kept getting worse and worse. A lot of innocent people were being affected,” he said. “I was seeing deaths – needless. If you give them any push back at all, they will shoot you.”

As a deterrent to counter this “easy crime,” he invented the Yates Device, an alarm system designed to prevent or interrupt carjacking. The driver can activate a switch located beneath the foot pedal or an app on the phone to trigger a programmed high-decibel alarm. Critically, it allows the carjacker to drive a safe distance away from the victim before it starts going off.

The alarm “turns your car into a very noisy Christmas tree on a time delay,” Dr. Yates explained. An external siren blares “stolen vehicle” repeatedly. A camera records everything in the car. Lights flash. Only the original driver can turn off the system. Later, once the car is abandoned, the police can help recover the vehicle.

In Dr. Yates’ experience, the invention process takes longer than you think. He worked through earlier iterations with strobe lights, but these could lead to bystanders getting hurt if the carjacker couldn’t see, for example. Developing the final product and applying for patents was a two-part process.

“The first is part is a pending patent phase, which secures your place in line,” he said. “After 1 year, we filed the utility patent as the final documentation that the invention is truly unique. That has been in process for a year now and the attorneys say we should receive approval soon.”

The product has initially been tested in seven cars for about 1 year. Dr. Yates is measuring how the system performs in all types of weather, including Chicago’s below-zero temperatures. The product is not available to the public for purchase yet because Dr. Yates is still seeking funding to have it mass produced, but it is currently being evaluated by Korean automakers for their car manufacturers.

“Everybody was saying ‘Let’s do something about this,’ but I didn’t see anybody doing anything yet,” Dr. Yates recalled. In the surgeon’s lounge, everybody has ideas. “You go around the room, and every doctor would have five ideas that would make them the richest doctor, but nobody takes it beyond that stage – talk. You have to synthesize that into a plan, to take action.”

Dr. Yates said that many doctors have the intellect to invent, but they aren’t in a network like entrepreneurs to bring their ideas to life.

For Dr. Yates, it takes a curious mindset to solve these daunting problems. “I’m always curious, always looking for how to improve something, to get better outcomes you have to be asking questions and just never let it go.”
 

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

WakeMed emergency department physician and medical director, Graham Snyder, MD, has seen his fair share of deaths: an average of one or two per day. That’s part of the job. Some of the deaths were the result of risky behavior, ongoing health problems, and other natural causes.

But what he didn’t find acceptable was losing a 6-year-old girl in a backyard pool drowning at what was meant to be a celebratory birthday party and family reunion.

“There were aunts and uncles and brothers and sisters and cousins, and the pool was packed, and they’re having a great time. One of the parents looked over and saw that she was swimming around underneath but acting weird. A relative pulled her up by the arm, and she was dead,” he said. “What nobody could tell me, and what they’ll live with the rest of their life, is how long was she under water?”

So Dr. Snyder invented a solution. The catch: He’s among an interesting set of doctors whose side gigs are solving critical problems affecting patients where they live. These are not medical devices for clinical use. They’re innovative products that everyday folks can use to make their lives safer and healthier. The goal: Improving systemic and “unsolvable” issues that harm society.

The cool part: Any MD with an idea can get in on the game.
 

Keeping little heads above water

Drowning is the leading cause of death in young children ages 1-4 years, and the second leading cause for children ages 5-14 years. The issue, Dr. Snyder explained, is not that rescuers couldn’t get to these children in time. “It’s that nobody knew to start looking.”

Dr. Snyder created a collar that alerts those around the swimmer that they are in trouble. The SEAL SwimSafe drowning prevention technology sets off an alarm system if a child is under water for too long. The necklace has been used to protect more than 10,000 children, including at larger swim facilities, such as the YMCA. 

When Dr. Snyder first started pursuing his invention, he asked himself two key questions: “Has someone already tried this? And if they did, why did they not succeed?” These questions help counteract the potential arrogance, he says, with imagining that you are the first person to have a certain idea. And using whatever reason others didn’t succeed as your “secret sauce” helps lead to more success. He also had to consider obstacles. People might resist wearing a collar or necklace while swimming or putting one on their child, like the reluctance around wearing bicycle helmets when they gained popularity in the 1980s. He concluded that the collars would work best at larger facilities, where they were mandated.

Another obstacle was false alarms. “It was possible to trigger a false alarm, and that could really scare people,” Dr. Snyder said. He is still considering systems to prevent the collars from being stolen or from “13-year-old boys hiding them in the water drain and making everyone really scared when an alarm is going off.”

The demand is real, however, and is based on alarming data. Safe Kids has reported that 66% of natural water drownings and around half of pool drownings happened with an adult supervising. They added, however, that supervision is often lacking or insufficient, such as a parent not being within arm’s reach of a young kid. As Dr. Snyder told reporters in a 2018 story, even the most well-intentioned parents still “miss something” sometimes, and this technology is for that moment.

“This is a completely solvable problem, but not a flip-a-switch, one and done,” he said, pointing to his product as a part of a more comprehensive approach, such as in Europe, where mandated public school swimming lessons are helping to decrease drowning deaths.

The pandemic slowed progress for the SEAL SwimSafe collar, which is currently waiting on a new funder or investor to take the reins. But the concept is alive and well with competitors pursuing related ideas. Dr. Snyder is holding out hope that entrepreneurs, scientists, public health workers, researchers, and others will be interested in continuing this work.
 

Eliminating the stigma of incontinence

Ever had an accident before making it to the bathroom? So have two-thirds of adult women, and almost one-third of older men. Incontinence is linked to a wide variety of conditions, from pelvic-floor trauma to neurological issues to diabetes, and others. Urologist Jessica Lubahn, MD, in Portland, Ore., saw one too many patients feeling this type of shame, unaware that the condition was so common. In addition, she personally experienced childbirth-related incontinence, and helped a relative who was having incontinence after prostate cancer surgery.

“He had a great result, but he had confided in me ... it was one of the only times in his life that he’s been truly depressed,” Dr. Lubahn said. “It’s not even the amount of leakage, but the smell, the stigma is so embarrassing, that not only is it an inconvenience, but [it affects] your entire psyche.” She thought there had to be a better solution than the “demeaning” act of wearing adult diapers.

Noting the explosion of the period panty industry in the past decade, Dr. Lubahn wanted to “destigmatize” incontinence in the same way menstruation education and products have been. She created ONDR incontinence underwear, specifically meant for urine, to ease the mental and physical burden on her patients and many others.

Dr. Lubahn said a process happens when you decide to start talking about the product you want to make rather than trying to find answers on your own. “A lot of people are so afraid to talk about their ideas because they’re afraid it’s going to get stolen or scooped, or it might fail,” she said. “I just openly discussed it, kind of like cocktail party conversation – ‘Wouldn’t it be funny if you just pee into your underwear?’ ” She noticed each connection led to finding more people to help her along her journey.

Dr. Lubahn studied the apparel industry, learning that overseas manufacturers were more helpful and cost-effective. She navigated issues such as a special stitch that prevented leakage and other details. She was also intent on using eco-friendly products that offset the environmental impact of pads, liners, and diapers. She said there’s a strong entrepreneurship community that can help other physician-inventors get grants, be part of accelerator programs, and receive support.

Six years after the original idea, Dr. Lubahn’s product was released in 2020. She now sells eight types of underwear for women and men’s boxer briefs. She wears them herself daily.
 

Deterring carjackers, saving lives

In 2022, carjackings tripled in Chicago and Memphis. The areas have the highest rates in 30 cities that the Council on Criminal Justice analyzed in a report on pandemic crime rates. According to the report, nearly 40% of offenders used a firearm, more than a quarter of victims were injured, and only around half of the vehicles taken were recovered. In addition, vehicles are sometimes used in secondary crimes, such as drive-by shootings. William Yates, MD, former trauma surgeon, now turned hair restoration surgeon in Chicago, saw the evidence of those crimes daily.

“I was perplexed by carjacking because there wasn’t any answer, and it just kept getting worse and worse. A lot of innocent people were being affected,” he said. “I was seeing deaths – needless. If you give them any push back at all, they will shoot you.”

As a deterrent to counter this “easy crime,” he invented the Yates Device, an alarm system designed to prevent or interrupt carjacking. The driver can activate a switch located beneath the foot pedal or an app on the phone to trigger a programmed high-decibel alarm. Critically, it allows the carjacker to drive a safe distance away from the victim before it starts going off.

The alarm “turns your car into a very noisy Christmas tree on a time delay,” Dr. Yates explained. An external siren blares “stolen vehicle” repeatedly. A camera records everything in the car. Lights flash. Only the original driver can turn off the system. Later, once the car is abandoned, the police can help recover the vehicle.

In Dr. Yates’ experience, the invention process takes longer than you think. He worked through earlier iterations with strobe lights, but these could lead to bystanders getting hurt if the carjacker couldn’t see, for example. Developing the final product and applying for patents was a two-part process.

“The first is part is a pending patent phase, which secures your place in line,” he said. “After 1 year, we filed the utility patent as the final documentation that the invention is truly unique. That has been in process for a year now and the attorneys say we should receive approval soon.”

The product has initially been tested in seven cars for about 1 year. Dr. Yates is measuring how the system performs in all types of weather, including Chicago’s below-zero temperatures. The product is not available to the public for purchase yet because Dr. Yates is still seeking funding to have it mass produced, but it is currently being evaluated by Korean automakers for their car manufacturers.

“Everybody was saying ‘Let’s do something about this,’ but I didn’t see anybody doing anything yet,” Dr. Yates recalled. In the surgeon’s lounge, everybody has ideas. “You go around the room, and every doctor would have five ideas that would make them the richest doctor, but nobody takes it beyond that stage – talk. You have to synthesize that into a plan, to take action.”

Dr. Yates said that many doctors have the intellect to invent, but they aren’t in a network like entrepreneurs to bring their ideas to life.

For Dr. Yates, it takes a curious mindset to solve these daunting problems. “I’m always curious, always looking for how to improve something, to get better outcomes you have to be asking questions and just never let it go.”
 

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

Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space. 

“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin. 

Thoroughly coating that cavity with medication can result in rapid, efficient absorption, making the nose’s inner chamber an attractive target for drug delivery.

“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.” 

It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route. 

But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.

The upshot: Someday, inhaling therapies could be as routine as swallowing pills. 

The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion. 

But there are challenges. 
 

How hard can it be?

Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond. 

These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020  Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land. 

Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.

The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.

Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”

Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions. 

Still, the benefits are enough to compel researchers to find a way in.

“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”


 

Delivering the goods

In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.

The results convinced Mr. Hoekman to stake his future on nasal drug delivery.

In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED. 

But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.

The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.

Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.

“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”

The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.

In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation. 
 

Targeting the brain

Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors. 

“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman. 

By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system. 

Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.

But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area. 

Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle. 

While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body. 

“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman. 

Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
 

A needle-free option 

Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed. 

This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.

Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination. 

There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels. 

This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics. 

The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
 

Inhaling protection against viruses

Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis. 

FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year. 

Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.” 

For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine. 

Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.

“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.

Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”

 

And yes, a nasal COVID vaccine is on the way

In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.

It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose. 

By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose. 

Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces. 

Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions. 

In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”

Novel applications like this represent the future of nasal drug delivery. 

“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”

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

Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space. 

“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin. 

Thoroughly coating that cavity with medication can result in rapid, efficient absorption, making the nose’s inner chamber an attractive target for drug delivery.

“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.” 

It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route. 

But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.

The upshot: Someday, inhaling therapies could be as routine as swallowing pills. 

The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion. 

But there are challenges. 
 

How hard can it be?

Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond. 

These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020  Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land. 

Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.

The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.

Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”

Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions. 

Still, the benefits are enough to compel researchers to find a way in.

“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”


 

Delivering the goods

In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.

The results convinced Mr. Hoekman to stake his future on nasal drug delivery.

In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED. 

But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.

The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.

Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.

“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”

The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.

In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation. 
 

Targeting the brain

Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors. 

“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman. 

By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system. 

Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.

But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area. 

Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle. 

While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body. 

“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman. 

Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
 

A needle-free option 

Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed. 

This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.

Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination. 

There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels. 

This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics. 

The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
 

Inhaling protection against viruses

Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis. 

FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year. 

Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.” 

For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine. 

Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.

“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.

Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”

 

And yes, a nasal COVID vaccine is on the way

In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.

It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose. 

By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose. 

Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces. 

Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions. 

In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”

Novel applications like this represent the future of nasal drug delivery. 

“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”

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

Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space. 

“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin. 

Thoroughly coating that cavity with medication can result in rapid, efficient absorption, making the nose’s inner chamber an attractive target for drug delivery.

“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.” 

It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route. 

But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.

The upshot: Someday, inhaling therapies could be as routine as swallowing pills. 

The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion. 

But there are challenges. 
 

How hard can it be?

Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond. 

These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020  Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land. 

Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.

The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.

Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”

Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions. 

Still, the benefits are enough to compel researchers to find a way in.

“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”


 

Delivering the goods

In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.

The results convinced Mr. Hoekman to stake his future on nasal drug delivery.

In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED. 

But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.

The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.

Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.

“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”

The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.

In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation. 
 

Targeting the brain

Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors. 

“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman. 

By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system. 

Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.

But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area. 

Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle. 

While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body. 

“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman. 

Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
 

A needle-free option 

Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed. 

This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.

Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination. 

There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels. 

This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics. 

The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
 

Inhaling protection against viruses

Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis. 

FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year. 

Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.” 

For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine. 

Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.

“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.

Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”

 

And yes, a nasal COVID vaccine is on the way

In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.

It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose. 

By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose. 

Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces. 

Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions. 

In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”

Novel applications like this represent the future of nasal drug delivery. 

“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”

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

Is it time to start recommending regular sauna bathing to improve heart health?

Mounting evidence shows that hitting the heated chambers can produce some of the same cardiovascular benefits as aerobic exercise. While a post-workout sauna can compound the benefits of exercise, the hormetic effects of heat therapy alone can produce significant gains for microvascular and endothelial function, no workout required.

“There’s enough evidence to say that regular sauna use improves cardiovascular health,” Matthew S. Ganio, PhD, a professor of exercise science at the University of Arkansas in Fayetteville, who studies thermoregulatory responses and cardiovascular health, said.

“The more they used it, the greater the reduction in cardiovascular events like heart attack. But you don’t need to be in there more than 20-30 minutes. That’s where it seemed to have the best effect,” Dr. Ganio said, adding that studies have shown a dose-response.

A prospective cohort study published in 2015 in JAMA Internal Medicine included 20 years of data on more than 2,300 Finnish men who regularly sauna bathed. The researchers found that among participants who sat in saunas more frequently, rates of death from heart disease and stroke were lower than among those who did so less often.
 

Cutaneous vasodilation

The body experiences several physiologic changes when exposed to heat therapy of any kind, including sauna, hot water submerging, shortwave diathermy, and heat wrapping. Many of these changes involve elements of the cardiovascular system, said Earric Lee, PhD, an exercise physiologist and postdoctoral researcher at the University of Jyväskylä in Finland, who has studied the effects of sauna on cardiovascular health.

The mechanisms by which heat therapy improves cardiovascular fitness have not been determined, as few studies of sauna bathing have been conducted to this degree. One driver appears to be cutaneous vasodilation. To cool the body when exposed to extreme external heat, cutaneous vessels dilate and push blood to the skin, which lowers body temperature, increases heart rate, and delivers oxygen to muscles in the limbs in a way similar to aerobic exercise.

Sauna bathing has similar effects on heart rate and cardiac output. Studies have shown it can improve the circulation of blood through the body, as well as vascular endothelial function, which is closely tied to vascular tone.

“Increased cardiac output is one of the physiologic reasons sauna is good for heart health,” Dr. Ganio said.

During a sauna session, cardiac output can increase by as much as 70% in relation to elevated heart rate. And while heart rate and cardiac output rise, stroke volume remains stable. As stroke volume increases, the effort that muscle must exert increases. When heart rate rises, stroke volume often falls, which subjects the heart to less of a workout and reduces the amount of oxygen and blood circulating throughout the body.

Heat therapy also temporarily increases blood pressure, but in a way similar to exercise, which supports better long-term heart health, said Christopher Minson, PhD, the Kenneth M. and Kenda H. Singer Endowed Professor of Human Physiology at the University of Oregon in Eugene.

A small study of 19 healthy adults that was published in Complementary Therapies in Medicine in 2019 found that blood pressure and heart rate rose during a 25-minute sauna session as they might during moderate exercise, equivalent to an exercise load of about 60-100 watts. These parameters then steadily decreased for 30 minutes after the sauna. An earlier study found that in the long term, blood pressure was lower after a sauna than before a sauna.
 

Upregulated heat shock proteins

Both aerobic exercise and heat stress from sauna bathing increase the activity of heat shock proteins. A 2021 review published in Experimental Gerontology found that heat shock proteins become elevated in cells within 30 minutes of exposure to heat and remain elevated over time – an effect similar to exercise.

“Saunas increase heat shock proteins that break down old, dysfunctional proteins and then protect new proteins from becoming dysfunctional,” Hunter S. Waldman, PhD, an assistant professor of exercise science at the University of North Alabama in Florence, said. This effect is one way sauna bathing may quell systemic inflammation, Dr. Waldman said.

According to a 2018 review published in BioMed Research International, an abundance of heat shock proteins may increase exercise tolerance. The researchers concluded that the positive stress associated with elevated body temperature could help people be physically active for longer periods.

Added stress, especially heat-related strain, is not good for everyone, however. Dr. Waldman cautioned that heat exposure, be it through a sauna, hot tub, or other source, can be harmful for pregnant women and children and can be dangerous for people who have low blood pressure, since blood pressure often drops to rates that are lower than before taking a sauna. It also can impair semen quality for months after exposure, so people who are trying to conceive should avoid sauna bathing.

Anyone who has been diagnosed with a heart condition, including cardiac arrhythmia, coronary artery disease, and congestive heart failure, should always consult their physician prior to using sauna for the first time or before using it habitually, Dr. Lee said.
 

Effects compounded by exercise

Dr. Minson stressed that any type of heat therapy should be part of a lifestyle that includes mostly healthy habits overall, especially a regular exercise regime when possible.

“You have to have everything else working as well: finding time to relax, not being overly stressed, staying hydrated – all those things are critical with any exercise training and heat therapy program,” he said.

Dr. Lee said it’s easy to overhype the benefits of sauna bathing and agreed the practice should be used in tandem with other therapies, not as a replacement. So far, stacking research has shown it to be an effective extension of aerobic exercise.

A June 2023 review published in Mayo Clinic Proceedings found that while sauna bathing can produce benefits on its own, a post-workout sauna can extend the benefits of exercise. As a result, the researchers concluded, saunas likely provide the most benefit when combined with aerobic and strength training.

While some of the benefits of exercise overlap those associated with sauna bathing, “you’re going to get some benefits with exercise that you’re never going to get with sauna,” Dr. Ganio said.

For instance, strength training or aerobic exercise usually results in muscle contractions, which sauna bathing does not produce.

If a person is impaired in a way that makes exercise difficult, taking a sauna after aerobic activity can extend the cardiovascular benefits of the workout, even if muscle-building does not occur, Dr. Lee said.

“All other things considered, especially with aerobic exercise, it is very comparable, so we can look at adding sauna bathing post exercise as a way to lengthen the aerobic exercise workout,” he said. “It’s not to the same degree, but you can get many of the ranging benefits of exercising simply by going into the sauna.”

The authors have disclosed no relevant financial relationships.

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