Cardiology News

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

During a family medicine rotation at Oregon Health & Sciences University, Portland, third-year medical students are preparing for a patient visit. Only, instead of entering a clinic room, students sit down at a computer. The patient they’re virtually examining – a 42-year-old male cattle rancher with knee problems – is an actor.

He asks for an MRI. A student explains that kneecap pain calls for rehab rather than a scan. The patient pushes back. “It would ease my mind,” he says. “I really need to make sure I can keep the ranch running.” The student must now try to digitally maintain rapport while explaining why imaging isn’t necessary.

When COVID-19 hit, telehealth training and remote learning became major parts of medical education, seemingly overnight. Since the start of the pandemic, students have contended with canceled classes, missed rotations, and revised training timelines, even as the demand for new doctors grows ever more pressing.

Institutions have been forced to rethink how to best establish solid, long-term foundations to ensure that young doctors are adequately trained. “They may find themselves the only doctors to be practicing in a small town,” said Stephen G. Post, PhD, bioethicist and professor at Stony Brook (N.Y.) University. “They have to be ready.”

With limited hands-on access to patients, students must learn in ways most never have before. Medical schools are now test-driving a mix of new and reimagined teaching strategies that aim to produce doctors who will enter medicine just as prepared as their more seasoned peers.

Hands-off education

Soon after starting her pediatrics rotation in March, recent Stanford (Calif.) University graduate Paloma Marin-Nevarez, MD, heard that children were being admitted to her hospital for evaluation to rule out COVID-19. Dr. Marin-Nevarez was assigned to help care for them but never physically met any – an approach called “virtual rounding.”

In virtual rounding, a provider typically goes in, examines a patient, and uses a portable device such as an iPad to send video or take notes about the encounter. Students or others in another room then give input on the patient’s care. “It was bizarre doing rounds on patients I had not met yet, discussing their treatment plans in one of the team rooms,” Dr. Marin-Nevarez said. “There was something very eerie about passing that particular unit that said: ‘Do not enter,’ and never being able to go inside.”

Within weeks, the Association of American Medical Colleges advised medical schools to suspend any activities – including clinical rotations – that involved direct student contact with patients, even those who weren’t COVID-19 positive.

Many schools hope to have students back and participating in some degree of patient care at non–COVID-19 hospital wards as early as July 1, said Michael Gisondi, MD, vice chair of education at Stanford’s department of emergency medicine. Returning students must now adapt to a restricted training environment, often while scrambling to make up training time. “This is uncharted territory for medical schools. Elective cases are down, surgical cases are down. That’s potentially going to decrease exposure to training opportunities.”

When students come back, lectures are still likely to remain on hold at most schools, replaced by Zoom conferences and virtual presentations. That’s not completely new: A trend away from large, traditional classes predated the pandemic. In a 2017-2018 AAMC survey, one in four second-year medical students said they almost never went to in-person lectures. COVID-19 has accelerated this shift.

For faculty who have long emphasized hands-on, in-person learning, the shift presents “a whole pedagogical issue – you don’t necessarily know how to adjust your practices to an online format,” Dr. Gisondi said. Instructors have to be even more flexible in order to engage students. “Every week I ask the students: ‘What’s working? What’s not working?’ ” Dr. Gisondi said about his online classes. “We have to solicit feedback.”

Changes to lectures are the easy part, says Elisabeth Fassas, a second-year student at the University of Maryland, Baltimore County. Before the pandemic, she was taking a clinical medicine course that involved time in the hospital, something that helped link the academic with the practical. “You really get to see the stuff you’re learning being relevant: ‘Here’s a patient who has a cardiology problem,’ ” she said. “[Capturing] that piece of connection to what you’re working toward is going to be tricky, I think.”

Some students who graduated this past spring worry about that clinical time they lost. Many remain acutely conscious of specific knowledge gaps. “I did not get a ton of experience examining crying children or holding babies,” said Dr. Marin-Nevarez, who starts an emergency medicine residency this year. “I am going to have to be transparent with my future instructors and let them know I missed out because of the pandemic.”

Such knowledge gaps mean new doctors will have to make up ground, said Jeremiah Tao, MD, who trains ophthalmology residents at the University of California, Irvine. But Dr. Tao doesn’t see these setbacks as a major long-term problem. His residents are already starting to make up the patient hours they missed in the spring and are refining the skills that got short shrift earlier on. For eligibility, “most boards require a certain number of days of experience. But most of the message from our board is [that] they’re understanding, and they’re going to leave it to the program directors to declare someone competent.”

Robert Johnson, MD, dean of New Jersey Medical School, Newark, said short-term setbacks in training likely won’t translate into longer-term skill deficits. “What most schools have done is overprepare students. We’re sure they have acquired all the skills they need to practice.”

Closing the gaps

To fill existing knowledge gaps and prevent future deficits, institutions hope to strike a balance between keeping trainees safe and providing necessary on-site learning. In line with ongoing AAMC recommendations, which suggest schools curtail student involvement in direct patient care in areas with significant COVID-19 spread, virtual rounding will likely continue.

Many schools may use a hybrid approach, in which students take turns entering patient rooms to perform checkups or observations while other students and instructors watch a video broadcast. “It’s not that different from when I go into the room and supervise a trainee,” Dr. Gisondi said.

Some schools are going even further, transforming education in ways that reflect the demands of a COVID-19–era medical marketplace. Institutions such as Weill Cornell Medicine, New York, and OHSU have invested in telemedicine training for years, but COVID-19 has given telehealth education an additional boost. These types of visits have surged dramatically, underscoring the importance of preparing new doctors to practice in a virtual setting – something that wasn’t common previously. In a 2019 survey, only about a quarter of sampled medical schools offered a telemedicine curriculum.

Simulated telehealth consults such as OHSU’s knee-pain scenario serve several purposes, says Ryan Palmer, EdD, associate dean of education at Northeast Ohio Universities, Rootstown. They virtually teach skills that students need – such as clearly explaining to patients why a care plan is called for – while allowing the trainees to practice forging an emotional connection with patients they are treating remotely.

“It’s less about how you use a specific system,” said Dr. Palmer, who developed OHSU’s TeleOSCE, a telehealth training system that has interested other schools. He sees this as an opportunity, inasmuch as telemedicine is likely to remain an important part of practice for the foreseeable future.

To that end, the AAMC recently hosted an online seminar to help faculty with telehealth instruction. But training such as this can only go so far, said Dr. Johnson. “There are techniques you do have to learn at the patient’s side.”

Dr. Johnson says that a traditional part of medical school at Rutgers has been having students spend time in general practitioners’ offices early on to see what the experience is like. “That’s going to be a problem – I expect many primary care practices will go out of business. Those types of shadowing experiences will probably go away. They may be replaced by experiences at larger clinics.”

Some learning in clinics may soon resume. Although fears about COVID-19 still loom large, Dr. Tao’s ophthalmology residents have started taking on something closer to a normal workload, thanks to patients returning for regular office visits. As people return to medical facilities in larger numbers, hospitals around the country have started separating patients with COVID-19 from others. Dr. Gisondi suggested that this means medical students may be able to circulate in non–COVID-19 wards, provided the institution has enough personal protective equipment. “The inpatient wards are really safe – there’s a low risk of transmission. That’s where core rotations occur.”

The road ahead

In settings where patients’ viral status remains uncertain, such as emergency wards and off-site clinics without rapid testing, in-person learning may be slower to resume. That’s where longer-term changes may come into play. Some schools are preparing digital learning platforms that have the potential to transform medical education.

For example, Haru Okuda, MD, an emergency medicine doctor and director of the Center for Advanced Medical Learning and Simulation at the University of South Florida, Tampa, is testing a new virtual-reality platform called Immertec. Dr. Okuda said that, unlike older teaching tools, the system is not a stale, static virtual environment that will become obsolete. Instead, it uses a live camera to visually teleport students into the space of a real clinic or operating room.

“Let’s say you have students learning gross anatomy, how to dissect the chest. You’d have a cadaver on the table, demonstrating anatomy. The student has a headset – you can see like you’re in the room.” The wraparound visual device allows students to watch surgical maneuvers close up or view additional input from devices such as laparoscopes.

Dr. Okuda acknowledges that educators don’t yet know whether this works as well as older, hands-on methods. As yet, no virtual reality system has touch-based sensors sophisticated enough to simulate even skills such as tying a basic surgical knot, Dr. Gisondi said. And immersive platforms are expensive, which means a gap may occur between schools that can afford them and those that can’t.

The long-term consequences of COVID-19 go beyond costs that institutions may have to bear. Some students are concerned that the pandemic is affecting their mental well-being in ways that may make training a tougher slog. A few students graduated early to serve on the COVID-19 front lines. Others, rather than planning trips to celebrate the gap between medical school and residency, watched from home as young doctors they knew worked under abusive and unsafe conditions.

“Many of us felt powerless, given what we saw happening around us,” said recent University of Michigan, Ann Arbor, graduate Marina Haque, MD. She thinks those feelings, along with the rigors of practicing medicine during a pandemic, may leave her and her colleagues more prone to burnout.

The pandemic has also had a galvanizing effect on students – some excited new doctors are eager to line up for duty on COVID-19 wards. But supervisors say they must weigh young doctors’ desire to serve against the possible risks. “You don’t want people who have a big future ahead of them rushing into these situations and getting severely ill,” said Dr. Post. “There is a balance.”

All these changes, temporary or lasting, have led many to question whether doctors who complete their training under the cloud of the pandemic will be more – or less – prepared than those who came before them. But it’s not really a question of better or worse, says Dr. Johnson, who stresses that medical education has always required flexibility.

“You come into medicine with a plan in mind, but things happen,” he said. He reflected on the HIV pandemic of the late 1980s and early 1990s that influenced his medical career. He hopes young doctors come through the COVID-19 crucible more seasoned, resilient, and confident in crisis situations. “This is a pivotal event in their lives, and it will shape many careers.”

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

During a family medicine rotation at Oregon Health & Sciences University, Portland, third-year medical students are preparing for a patient visit. Only, instead of entering a clinic room, students sit down at a computer. The patient they’re virtually examining – a 42-year-old male cattle rancher with knee problems – is an actor.

He asks for an MRI. A student explains that kneecap pain calls for rehab rather than a scan. The patient pushes back. “It would ease my mind,” he says. “I really need to make sure I can keep the ranch running.” The student must now try to digitally maintain rapport while explaining why imaging isn’t necessary.

When COVID-19 hit, telehealth training and remote learning became major parts of medical education, seemingly overnight. Since the start of the pandemic, students have contended with canceled classes, missed rotations, and revised training timelines, even as the demand for new doctors grows ever more pressing.

Institutions have been forced to rethink how to best establish solid, long-term foundations to ensure that young doctors are adequately trained. “They may find themselves the only doctors to be practicing in a small town,” said Stephen G. Post, PhD, bioethicist and professor at Stony Brook (N.Y.) University. “They have to be ready.”

With limited hands-on access to patients, students must learn in ways most never have before. Medical schools are now test-driving a mix of new and reimagined teaching strategies that aim to produce doctors who will enter medicine just as prepared as their more seasoned peers.

Hands-off education

Soon after starting her pediatrics rotation in March, recent Stanford (Calif.) University graduate Paloma Marin-Nevarez, MD, heard that children were being admitted to her hospital for evaluation to rule out COVID-19. Dr. Marin-Nevarez was assigned to help care for them but never physically met any – an approach called “virtual rounding.”

In virtual rounding, a provider typically goes in, examines a patient, and uses a portable device such as an iPad to send video or take notes about the encounter. Students or others in another room then give input on the patient’s care. “It was bizarre doing rounds on patients I had not met yet, discussing their treatment plans in one of the team rooms,” Dr. Marin-Nevarez said. “There was something very eerie about passing that particular unit that said: ‘Do not enter,’ and never being able to go inside.”

Within weeks, the Association of American Medical Colleges advised medical schools to suspend any activities – including clinical rotations – that involved direct student contact with patients, even those who weren’t COVID-19 positive.

Many schools hope to have students back and participating in some degree of patient care at non–COVID-19 hospital wards as early as July 1, said Michael Gisondi, MD, vice chair of education at Stanford’s department of emergency medicine. Returning students must now adapt to a restricted training environment, often while scrambling to make up training time. “This is uncharted territory for medical schools. Elective cases are down, surgical cases are down. That’s potentially going to decrease exposure to training opportunities.”

When students come back, lectures are still likely to remain on hold at most schools, replaced by Zoom conferences and virtual presentations. That’s not completely new: A trend away from large, traditional classes predated the pandemic. In a 2017-2018 AAMC survey, one in four second-year medical students said they almost never went to in-person lectures. COVID-19 has accelerated this shift.

For faculty who have long emphasized hands-on, in-person learning, the shift presents “a whole pedagogical issue – you don’t necessarily know how to adjust your practices to an online format,” Dr. Gisondi said. Instructors have to be even more flexible in order to engage students. “Every week I ask the students: ‘What’s working? What’s not working?’ ” Dr. Gisondi said about his online classes. “We have to solicit feedback.”

Changes to lectures are the easy part, says Elisabeth Fassas, a second-year student at the University of Maryland, Baltimore County. Before the pandemic, she was taking a clinical medicine course that involved time in the hospital, something that helped link the academic with the practical. “You really get to see the stuff you’re learning being relevant: ‘Here’s a patient who has a cardiology problem,’ ” she said. “[Capturing] that piece of connection to what you’re working toward is going to be tricky, I think.”

Some students who graduated this past spring worry about that clinical time they lost. Many remain acutely conscious of specific knowledge gaps. “I did not get a ton of experience examining crying children or holding babies,” said Dr. Marin-Nevarez, who starts an emergency medicine residency this year. “I am going to have to be transparent with my future instructors and let them know I missed out because of the pandemic.”

Such knowledge gaps mean new doctors will have to make up ground, said Jeremiah Tao, MD, who trains ophthalmology residents at the University of California, Irvine. But Dr. Tao doesn’t see these setbacks as a major long-term problem. His residents are already starting to make up the patient hours they missed in the spring and are refining the skills that got short shrift earlier on. For eligibility, “most boards require a certain number of days of experience. But most of the message from our board is [that] they’re understanding, and they’re going to leave it to the program directors to declare someone competent.”

Robert Johnson, MD, dean of New Jersey Medical School, Newark, said short-term setbacks in training likely won’t translate into longer-term skill deficits. “What most schools have done is overprepare students. We’re sure they have acquired all the skills they need to practice.”

Closing the gaps

To fill existing knowledge gaps and prevent future deficits, institutions hope to strike a balance between keeping trainees safe and providing necessary on-site learning. In line with ongoing AAMC recommendations, which suggest schools curtail student involvement in direct patient care in areas with significant COVID-19 spread, virtual rounding will likely continue.

Many schools may use a hybrid approach, in which students take turns entering patient rooms to perform checkups or observations while other students and instructors watch a video broadcast. “It’s not that different from when I go into the room and supervise a trainee,” Dr. Gisondi said.

Some schools are going even further, transforming education in ways that reflect the demands of a COVID-19–era medical marketplace. Institutions such as Weill Cornell Medicine, New York, and OHSU have invested in telemedicine training for years, but COVID-19 has given telehealth education an additional boost. These types of visits have surged dramatically, underscoring the importance of preparing new doctors to practice in a virtual setting – something that wasn’t common previously. In a 2019 survey, only about a quarter of sampled medical schools offered a telemedicine curriculum.

Simulated telehealth consults such as OHSU’s knee-pain scenario serve several purposes, says Ryan Palmer, EdD, associate dean of education at Northeast Ohio Universities, Rootstown. They virtually teach skills that students need – such as clearly explaining to patients why a care plan is called for – while allowing the trainees to practice forging an emotional connection with patients they are treating remotely.

“It’s less about how you use a specific system,” said Dr. Palmer, who developed OHSU’s TeleOSCE, a telehealth training system that has interested other schools. He sees this as an opportunity, inasmuch as telemedicine is likely to remain an important part of practice for the foreseeable future.

To that end, the AAMC recently hosted an online seminar to help faculty with telehealth instruction. But training such as this can only go so far, said Dr. Johnson. “There are techniques you do have to learn at the patient’s side.”

Dr. Johnson says that a traditional part of medical school at Rutgers has been having students spend time in general practitioners’ offices early on to see what the experience is like. “That’s going to be a problem – I expect many primary care practices will go out of business. Those types of shadowing experiences will probably go away. They may be replaced by experiences at larger clinics.”

Some learning in clinics may soon resume. Although fears about COVID-19 still loom large, Dr. Tao’s ophthalmology residents have started taking on something closer to a normal workload, thanks to patients returning for regular office visits. As people return to medical facilities in larger numbers, hospitals around the country have started separating patients with COVID-19 from others. Dr. Gisondi suggested that this means medical students may be able to circulate in non–COVID-19 wards, provided the institution has enough personal protective equipment. “The inpatient wards are really safe – there’s a low risk of transmission. That’s where core rotations occur.”

The road ahead

In settings where patients’ viral status remains uncertain, such as emergency wards and off-site clinics without rapid testing, in-person learning may be slower to resume. That’s where longer-term changes may come into play. Some schools are preparing digital learning platforms that have the potential to transform medical education.

For example, Haru Okuda, MD, an emergency medicine doctor and director of the Center for Advanced Medical Learning and Simulation at the University of South Florida, Tampa, is testing a new virtual-reality platform called Immertec. Dr. Okuda said that, unlike older teaching tools, the system is not a stale, static virtual environment that will become obsolete. Instead, it uses a live camera to visually teleport students into the space of a real clinic or operating room.

“Let’s say you have students learning gross anatomy, how to dissect the chest. You’d have a cadaver on the table, demonstrating anatomy. The student has a headset – you can see like you’re in the room.” The wraparound visual device allows students to watch surgical maneuvers close up or view additional input from devices such as laparoscopes.

Dr. Okuda acknowledges that educators don’t yet know whether this works as well as older, hands-on methods. As yet, no virtual reality system has touch-based sensors sophisticated enough to simulate even skills such as tying a basic surgical knot, Dr. Gisondi said. And immersive platforms are expensive, which means a gap may occur between schools that can afford them and those that can’t.

The long-term consequences of COVID-19 go beyond costs that institutions may have to bear. Some students are concerned that the pandemic is affecting their mental well-being in ways that may make training a tougher slog. A few students graduated early to serve on the COVID-19 front lines. Others, rather than planning trips to celebrate the gap between medical school and residency, watched from home as young doctors they knew worked under abusive and unsafe conditions.

“Many of us felt powerless, given what we saw happening around us,” said recent University of Michigan, Ann Arbor, graduate Marina Haque, MD. She thinks those feelings, along with the rigors of practicing medicine during a pandemic, may leave her and her colleagues more prone to burnout.

The pandemic has also had a galvanizing effect on students – some excited new doctors are eager to line up for duty on COVID-19 wards. But supervisors say they must weigh young doctors’ desire to serve against the possible risks. “You don’t want people who have a big future ahead of them rushing into these situations and getting severely ill,” said Dr. Post. “There is a balance.”

All these changes, temporary or lasting, have led many to question whether doctors who complete their training under the cloud of the pandemic will be more – or less – prepared than those who came before them. But it’s not really a question of better or worse, says Dr. Johnson, who stresses that medical education has always required flexibility.

“You come into medicine with a plan in mind, but things happen,” he said. He reflected on the HIV pandemic of the late 1980s and early 1990s that influenced his medical career. He hopes young doctors come through the COVID-19 crucible more seasoned, resilient, and confident in crisis situations. “This is a pivotal event in their lives, and it will shape many careers.”

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

During a family medicine rotation at Oregon Health & Sciences University, Portland, third-year medical students are preparing for a patient visit. Only, instead of entering a clinic room, students sit down at a computer. The patient they’re virtually examining – a 42-year-old male cattle rancher with knee problems – is an actor.

He asks for an MRI. A student explains that kneecap pain calls for rehab rather than a scan. The patient pushes back. “It would ease my mind,” he says. “I really need to make sure I can keep the ranch running.” The student must now try to digitally maintain rapport while explaining why imaging isn’t necessary.

When COVID-19 hit, telehealth training and remote learning became major parts of medical education, seemingly overnight. Since the start of the pandemic, students have contended with canceled classes, missed rotations, and revised training timelines, even as the demand for new doctors grows ever more pressing.

Institutions have been forced to rethink how to best establish solid, long-term foundations to ensure that young doctors are adequately trained. “They may find themselves the only doctors to be practicing in a small town,” said Stephen G. Post, PhD, bioethicist and professor at Stony Brook (N.Y.) University. “They have to be ready.”

With limited hands-on access to patients, students must learn in ways most never have before. Medical schools are now test-driving a mix of new and reimagined teaching strategies that aim to produce doctors who will enter medicine just as prepared as their more seasoned peers.

Hands-off education

Soon after starting her pediatrics rotation in March, recent Stanford (Calif.) University graduate Paloma Marin-Nevarez, MD, heard that children were being admitted to her hospital for evaluation to rule out COVID-19. Dr. Marin-Nevarez was assigned to help care for them but never physically met any – an approach called “virtual rounding.”

In virtual rounding, a provider typically goes in, examines a patient, and uses a portable device such as an iPad to send video or take notes about the encounter. Students or others in another room then give input on the patient’s care. “It was bizarre doing rounds on patients I had not met yet, discussing their treatment plans in one of the team rooms,” Dr. Marin-Nevarez said. “There was something very eerie about passing that particular unit that said: ‘Do not enter,’ and never being able to go inside.”

Within weeks, the Association of American Medical Colleges advised medical schools to suspend any activities – including clinical rotations – that involved direct student contact with patients, even those who weren’t COVID-19 positive.

Many schools hope to have students back and participating in some degree of patient care at non–COVID-19 hospital wards as early as July 1, said Michael Gisondi, MD, vice chair of education at Stanford’s department of emergency medicine. Returning students must now adapt to a restricted training environment, often while scrambling to make up training time. “This is uncharted territory for medical schools. Elective cases are down, surgical cases are down. That’s potentially going to decrease exposure to training opportunities.”

When students come back, lectures are still likely to remain on hold at most schools, replaced by Zoom conferences and virtual presentations. That’s not completely new: A trend away from large, traditional classes predated the pandemic. In a 2017-2018 AAMC survey, one in four second-year medical students said they almost never went to in-person lectures. COVID-19 has accelerated this shift.

For faculty who have long emphasized hands-on, in-person learning, the shift presents “a whole pedagogical issue – you don’t necessarily know how to adjust your practices to an online format,” Dr. Gisondi said. Instructors have to be even more flexible in order to engage students. “Every week I ask the students: ‘What’s working? What’s not working?’ ” Dr. Gisondi said about his online classes. “We have to solicit feedback.”

Changes to lectures are the easy part, says Elisabeth Fassas, a second-year student at the University of Maryland, Baltimore County. Before the pandemic, she was taking a clinical medicine course that involved time in the hospital, something that helped link the academic with the practical. “You really get to see the stuff you’re learning being relevant: ‘Here’s a patient who has a cardiology problem,’ ” she said. “[Capturing] that piece of connection to what you’re working toward is going to be tricky, I think.”

Some students who graduated this past spring worry about that clinical time they lost. Many remain acutely conscious of specific knowledge gaps. “I did not get a ton of experience examining crying children or holding babies,” said Dr. Marin-Nevarez, who starts an emergency medicine residency this year. “I am going to have to be transparent with my future instructors and let them know I missed out because of the pandemic.”

Such knowledge gaps mean new doctors will have to make up ground, said Jeremiah Tao, MD, who trains ophthalmology residents at the University of California, Irvine. But Dr. Tao doesn’t see these setbacks as a major long-term problem. His residents are already starting to make up the patient hours they missed in the spring and are refining the skills that got short shrift earlier on. For eligibility, “most boards require a certain number of days of experience. But most of the message from our board is [that] they’re understanding, and they’re going to leave it to the program directors to declare someone competent.”

Robert Johnson, MD, dean of New Jersey Medical School, Newark, said short-term setbacks in training likely won’t translate into longer-term skill deficits. “What most schools have done is overprepare students. We’re sure they have acquired all the skills they need to practice.”

Closing the gaps

To fill existing knowledge gaps and prevent future deficits, institutions hope to strike a balance between keeping trainees safe and providing necessary on-site learning. In line with ongoing AAMC recommendations, which suggest schools curtail student involvement in direct patient care in areas with significant COVID-19 spread, virtual rounding will likely continue.

Many schools may use a hybrid approach, in which students take turns entering patient rooms to perform checkups or observations while other students and instructors watch a video broadcast. “It’s not that different from when I go into the room and supervise a trainee,” Dr. Gisondi said.

Some schools are going even further, transforming education in ways that reflect the demands of a COVID-19–era medical marketplace. Institutions such as Weill Cornell Medicine, New York, and OHSU have invested in telemedicine training for years, but COVID-19 has given telehealth education an additional boost. These types of visits have surged dramatically, underscoring the importance of preparing new doctors to practice in a virtual setting – something that wasn’t common previously. In a 2019 survey, only about a quarter of sampled medical schools offered a telemedicine curriculum.

Simulated telehealth consults such as OHSU’s knee-pain scenario serve several purposes, says Ryan Palmer, EdD, associate dean of education at Northeast Ohio Universities, Rootstown. They virtually teach skills that students need – such as clearly explaining to patients why a care plan is called for – while allowing the trainees to practice forging an emotional connection with patients they are treating remotely.

“It’s less about how you use a specific system,” said Dr. Palmer, who developed OHSU’s TeleOSCE, a telehealth training system that has interested other schools. He sees this as an opportunity, inasmuch as telemedicine is likely to remain an important part of practice for the foreseeable future.

To that end, the AAMC recently hosted an online seminar to help faculty with telehealth instruction. But training such as this can only go so far, said Dr. Johnson. “There are techniques you do have to learn at the patient’s side.”

Dr. Johnson says that a traditional part of medical school at Rutgers has been having students spend time in general practitioners’ offices early on to see what the experience is like. “That’s going to be a problem – I expect many primary care practices will go out of business. Those types of shadowing experiences will probably go away. They may be replaced by experiences at larger clinics.”

Some learning in clinics may soon resume. Although fears about COVID-19 still loom large, Dr. Tao’s ophthalmology residents have started taking on something closer to a normal workload, thanks to patients returning for regular office visits. As people return to medical facilities in larger numbers, hospitals around the country have started separating patients with COVID-19 from others. Dr. Gisondi suggested that this means medical students may be able to circulate in non–COVID-19 wards, provided the institution has enough personal protective equipment. “The inpatient wards are really safe – there’s a low risk of transmission. That’s where core rotations occur.”

The road ahead

In settings where patients’ viral status remains uncertain, such as emergency wards and off-site clinics without rapid testing, in-person learning may be slower to resume. That’s where longer-term changes may come into play. Some schools are preparing digital learning platforms that have the potential to transform medical education.

For example, Haru Okuda, MD, an emergency medicine doctor and director of the Center for Advanced Medical Learning and Simulation at the University of South Florida, Tampa, is testing a new virtual-reality platform called Immertec. Dr. Okuda said that, unlike older teaching tools, the system is not a stale, static virtual environment that will become obsolete. Instead, it uses a live camera to visually teleport students into the space of a real clinic or operating room.

“Let’s say you have students learning gross anatomy, how to dissect the chest. You’d have a cadaver on the table, demonstrating anatomy. The student has a headset – you can see like you’re in the room.” The wraparound visual device allows students to watch surgical maneuvers close up or view additional input from devices such as laparoscopes.

Dr. Okuda acknowledges that educators don’t yet know whether this works as well as older, hands-on methods. As yet, no virtual reality system has touch-based sensors sophisticated enough to simulate even skills such as tying a basic surgical knot, Dr. Gisondi said. And immersive platforms are expensive, which means a gap may occur between schools that can afford them and those that can’t.

The long-term consequences of COVID-19 go beyond costs that institutions may have to bear. Some students are concerned that the pandemic is affecting their mental well-being in ways that may make training a tougher slog. A few students graduated early to serve on the COVID-19 front lines. Others, rather than planning trips to celebrate the gap between medical school and residency, watched from home as young doctors they knew worked under abusive and unsafe conditions.

“Many of us felt powerless, given what we saw happening around us,” said recent University of Michigan, Ann Arbor, graduate Marina Haque, MD. She thinks those feelings, along with the rigors of practicing medicine during a pandemic, may leave her and her colleagues more prone to burnout.

The pandemic has also had a galvanizing effect on students – some excited new doctors are eager to line up for duty on COVID-19 wards. But supervisors say they must weigh young doctors’ desire to serve against the possible risks. “You don’t want people who have a big future ahead of them rushing into these situations and getting severely ill,” said Dr. Post. “There is a balance.”

All these changes, temporary or lasting, have led many to question whether doctors who complete their training under the cloud of the pandemic will be more – or less – prepared than those who came before them. But it’s not really a question of better or worse, says Dr. Johnson, who stresses that medical education has always required flexibility.

“You come into medicine with a plan in mind, but things happen,” he said. He reflected on the HIV pandemic of the late 1980s and early 1990s that influenced his medical career. He hopes young doctors come through the COVID-19 crucible more seasoned, resilient, and confident in crisis situations. “This is a pivotal event in their lives, and it will shape many careers.”

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

The World Health Organization is preparing a scientific brief to address the continually emerging evidence on transmission of COVID-19 and plans to release its guidance “in the coming days.”

WHO will likely address airborne transmission of the virus after a commentary from almost 240 multidisciplinary scientists raised the alarm that virus particles could remain airborne longer that previously appreciated, particularly in poorly ventilated indoor spaces.

“Airborne route of infection transmission is significant, but so far completely undermined, and not recognized by the decision makers and bodies responsible for infection control,” lead commentary author Lidia Morawska, PhD, told Medscape Medical News.

“This means that no control measures are taken to mitigate airborne transmission and, as a consequence, people are infected and can die,” said Morawska, director of the International Laboratory for Air Quality and Health at Queensland University of Technology in Brisbane, Australia. “We wanted to bring this to the attention of the world to prevent this from happening.”

The commentary was published July 6 in Clinical Infectious Diseases.

WHO leaders defended their progress in announcing any changes regarding how COVID-19 can be transmitted during a virtual press briefing today. They have collaborated since April with some of the scientists who coauthored the commentary, for example, said Maria Van Kerkhove, PhD, WHO technical lead on COVID-19.

“We have been working on a scientific brief ... to consolidate knowledge around transmission,” she added.

One focus will be on how masks protect healthcare workers. “We are also looking at the possible role of airborne transmission in other settings,” Van Kerkhove said. “We will be releasing our brief in the coming days.”

“We acknowledge there is emerging evidence in this field,” Benedetta Allegranzi, MD, WHO technical lead on COVID-19, said during the briefing from Geneva. “Therefore, we believe we have to be open to this evidence and its implications.”

WHO participated in an international research meeting last week that addressed means for controlling modes of COVID-19 transmission, Allegranzi said. “Our group and others really highlighted importance of research on different modes of transmission, including droplets of different sizes and their relative importance,” she said. Another aim was determining the dose of the virus required for airborne transmission.

“These fields of research are really growing but not definitive. More evidence needs to be gathered and evaluated,” she explained.

In the meantime, Allegranzi said, “the possibility of airborne transmission in public settings – especially closed, poorly ventilated settings – cannot be ruled out.”

Morawska said the evidence already exists. “A continuous surprise is that it takes the world such a long time to accept this, while this has such solid scientific foundation.” As an example, she cited an April report she coauthored in the journal Environment International. She and colleagues call for “national authorities to acknowledge the reality that the virus spreads through air and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.”

The take-home message from the commentary, Morawska said, is a call to action. The authors state there is a need “to provide sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and aged care homes.”

WHO Chief Scientist Soumya Swaminathan, MD, explained why the organization remains cautious about making premature pronouncements regarding airborne transmission. “Any guidance we put out has implications for billions of people around the world, so we want to be as careful as possible,” she said during the press briefing. “We have to consider the weight of the evidence.”

“We are constantly looking for information on how we can do better,” Swaminathan added. WHO officials are reviewing hundreds of scientific reports every day, she said, and not all are of good quality. For this reason, she and other scientists at WHO perform a “living systematic review” – updating the consensus of evidence on a weekly basis.  

“This process on COVID-19 will, I am sure, continue for the weeks and months to come,” she added.

This article first appeared on Medscape.com.

The World Health Organization is preparing a scientific brief to address the continually emerging evidence on transmission of COVID-19 and plans to release its guidance “in the coming days.”

WHO will likely address airborne transmission of the virus after a commentary from almost 240 multidisciplinary scientists raised the alarm that virus particles could remain airborne longer that previously appreciated, particularly in poorly ventilated indoor spaces.

“Airborne route of infection transmission is significant, but so far completely undermined, and not recognized by the decision makers and bodies responsible for infection control,” lead commentary author Lidia Morawska, PhD, told Medscape Medical News.

“This means that no control measures are taken to mitigate airborne transmission and, as a consequence, people are infected and can die,” said Morawska, director of the International Laboratory for Air Quality and Health at Queensland University of Technology in Brisbane, Australia. “We wanted to bring this to the attention of the world to prevent this from happening.”

The commentary was published July 6 in Clinical Infectious Diseases.

WHO leaders defended their progress in announcing any changes regarding how COVID-19 can be transmitted during a virtual press briefing today. They have collaborated since April with some of the scientists who coauthored the commentary, for example, said Maria Van Kerkhove, PhD, WHO technical lead on COVID-19.

“We have been working on a scientific brief ... to consolidate knowledge around transmission,” she added.

One focus will be on how masks protect healthcare workers. “We are also looking at the possible role of airborne transmission in other settings,” Van Kerkhove said. “We will be releasing our brief in the coming days.”

“We acknowledge there is emerging evidence in this field,” Benedetta Allegranzi, MD, WHO technical lead on COVID-19, said during the briefing from Geneva. “Therefore, we believe we have to be open to this evidence and its implications.”

WHO participated in an international research meeting last week that addressed means for controlling modes of COVID-19 transmission, Allegranzi said. “Our group and others really highlighted importance of research on different modes of transmission, including droplets of different sizes and their relative importance,” she said. Another aim was determining the dose of the virus required for airborne transmission.

“These fields of research are really growing but not definitive. More evidence needs to be gathered and evaluated,” she explained.

In the meantime, Allegranzi said, “the possibility of airborne transmission in public settings – especially closed, poorly ventilated settings – cannot be ruled out.”

Morawska said the evidence already exists. “A continuous surprise is that it takes the world such a long time to accept this, while this has such solid scientific foundation.” As an example, she cited an April report she coauthored in the journal Environment International. She and colleagues call for “national authorities to acknowledge the reality that the virus spreads through air and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.”

The take-home message from the commentary, Morawska said, is a call to action. The authors state there is a need “to provide sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and aged care homes.”

WHO Chief Scientist Soumya Swaminathan, MD, explained why the organization remains cautious about making premature pronouncements regarding airborne transmission. “Any guidance we put out has implications for billions of people around the world, so we want to be as careful as possible,” she said during the press briefing. “We have to consider the weight of the evidence.”

“We are constantly looking for information on how we can do better,” Swaminathan added. WHO officials are reviewing hundreds of scientific reports every day, she said, and not all are of good quality. For this reason, she and other scientists at WHO perform a “living systematic review” – updating the consensus of evidence on a weekly basis.  

“This process on COVID-19 will, I am sure, continue for the weeks and months to come,” she added.

This article first appeared on Medscape.com.

The World Health Organization is preparing a scientific brief to address the continually emerging evidence on transmission of COVID-19 and plans to release its guidance “in the coming days.”

WHO will likely address airborne transmission of the virus after a commentary from almost 240 multidisciplinary scientists raised the alarm that virus particles could remain airborne longer that previously appreciated, particularly in poorly ventilated indoor spaces.

“Airborne route of infection transmission is significant, but so far completely undermined, and not recognized by the decision makers and bodies responsible for infection control,” lead commentary author Lidia Morawska, PhD, told Medscape Medical News.

“This means that no control measures are taken to mitigate airborne transmission and, as a consequence, people are infected and can die,” said Morawska, director of the International Laboratory for Air Quality and Health at Queensland University of Technology in Brisbane, Australia. “We wanted to bring this to the attention of the world to prevent this from happening.”

The commentary was published July 6 in Clinical Infectious Diseases.

WHO leaders defended their progress in announcing any changes regarding how COVID-19 can be transmitted during a virtual press briefing today. They have collaborated since April with some of the scientists who coauthored the commentary, for example, said Maria Van Kerkhove, PhD, WHO technical lead on COVID-19.

“We have been working on a scientific brief ... to consolidate knowledge around transmission,” she added.

One focus will be on how masks protect healthcare workers. “We are also looking at the possible role of airborne transmission in other settings,” Van Kerkhove said. “We will be releasing our brief in the coming days.”

“We acknowledge there is emerging evidence in this field,” Benedetta Allegranzi, MD, WHO technical lead on COVID-19, said during the briefing from Geneva. “Therefore, we believe we have to be open to this evidence and its implications.”

WHO participated in an international research meeting last week that addressed means for controlling modes of COVID-19 transmission, Allegranzi said. “Our group and others really highlighted importance of research on different modes of transmission, including droplets of different sizes and their relative importance,” she said. Another aim was determining the dose of the virus required for airborne transmission.

“These fields of research are really growing but not definitive. More evidence needs to be gathered and evaluated,” she explained.

In the meantime, Allegranzi said, “the possibility of airborne transmission in public settings – especially closed, poorly ventilated settings – cannot be ruled out.”

Morawska said the evidence already exists. “A continuous surprise is that it takes the world such a long time to accept this, while this has such solid scientific foundation.” As an example, she cited an April report she coauthored in the journal Environment International. She and colleagues call for “national authorities to acknowledge the reality that the virus spreads through air and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.”

The take-home message from the commentary, Morawska said, is a call to action. The authors state there is a need “to provide sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and aged care homes.”

WHO Chief Scientist Soumya Swaminathan, MD, explained why the organization remains cautious about making premature pronouncements regarding airborne transmission. “Any guidance we put out has implications for billions of people around the world, so we want to be as careful as possible,” she said during the press briefing. “We have to consider the weight of the evidence.”

“We are constantly looking for information on how we can do better,” Swaminathan added. WHO officials are reviewing hundreds of scientific reports every day, she said, and not all are of good quality. For this reason, she and other scientists at WHO perform a “living systematic review” – updating the consensus of evidence on a weekly basis.  

“This process on COVID-19 will, I am sure, continue for the weeks and months to come,” she added.

This article first appeared on Medscape.com.

“Patients with type 2 diabetes should consider intermittent fasting carefully” and “not undertake it without the involvement of their physician,” stress the authors of a new viewpoint published online July 2 in JAMA.

This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.

Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.

The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.

Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.

“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.

Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”

The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
 

Intermittent fasting: Less safe than calorie restriction in diabetes?

Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.

Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”

Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.

They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.

Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.

They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.

But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.

Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.

Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.

However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).

The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”

“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”

Should continuous glucose monitoring to detect glycemic variability be considered?

Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.

“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.

Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.

Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.

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

“Patients with type 2 diabetes should consider intermittent fasting carefully” and “not undertake it without the involvement of their physician,” stress the authors of a new viewpoint published online July 2 in JAMA.

This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.

Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.

The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.

Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.

“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.

Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”

The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
 

Intermittent fasting: Less safe than calorie restriction in diabetes?

Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.

Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”

Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.

They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.

Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.

They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.

But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.

Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.

Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.

However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).

The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”

“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”

Should continuous glucose monitoring to detect glycemic variability be considered?

Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.

“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.

Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.

Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.

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

“Patients with type 2 diabetes should consider intermittent fasting carefully” and “not undertake it without the involvement of their physician,” stress the authors of a new viewpoint published online July 2 in JAMA.

This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.

Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.

The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.

Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.

“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.

Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”

The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
 

Intermittent fasting: Less safe than calorie restriction in diabetes?

Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.

Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”

Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.

They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.

Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.

They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.

But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.

Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.

Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.

However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).

The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”

“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”

Should continuous glucose monitoring to detect glycemic variability be considered?

Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.

“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.

Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.

Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.

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

Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.

These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.

One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.

The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.

Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.

HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.

As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.

“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”

Dr. Rabkin and Dr. Cohn had no disclosures.

[email protected]

Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.

These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.

One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.

The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.

Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.

HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.

As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.

“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”

Dr. Rabkin and Dr. Cohn had no disclosures.

[email protected]

Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.

These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.

One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.

The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.

Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.

HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.

As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.

“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”

Dr. Rabkin and Dr. Cohn had no disclosures.

[email protected]

People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.

“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.

“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”

The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”

The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.

One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.

The intersection of HIV and COVID-19 will be a major theme at the virtual meeting of the International AIDS conference. Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.

The New York City cohort

For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.

They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.

The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.

Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.

The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.

Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.

“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”

In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).

The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.

A surprise association

What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.

This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.

“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”

“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.

A “modest” increase

Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.

But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”

“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.

Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).

Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.

What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.

“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”

“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.

Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.

“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.

This article first appeared on Medscape.com.

People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.

“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.

“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”

The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”

The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.

One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.

The intersection of HIV and COVID-19 will be a major theme at the virtual meeting of the International AIDS conference. Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.

The New York City cohort

For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.

They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.

The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.

Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.

The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.

Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.

“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”

In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).

The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.

A surprise association

What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.

This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.

“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”

“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.

A “modest” increase

Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.

But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”

“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.

Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).

Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.

What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.

“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”

“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.

Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.

“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.

This article first appeared on Medscape.com.

People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.

“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.

“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”

The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”

The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.

One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.

The intersection of HIV and COVID-19 will be a major theme at the virtual meeting of the International AIDS conference. Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.

The New York City cohort

For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.

They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.

The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.

Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.

The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.

Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.

“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”

In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).

The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.

A surprise association

What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.

This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.

“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”

“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.

A “modest” increase

Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.

But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”

“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.

Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).

Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.

What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.

“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”

“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.

Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.

“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.

This article first appeared on Medscape.com.

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.