Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.

Patients in the United States continue to experience rising out-of-pocket medical costs, with little access to the price information they desire when making decisions regarding medical care.¹ The Centers for Medicare & Medicaid Services (CMS) has taken steps toward transparency by requiring hospitals to publish price information.² In this issue of the Journal of Hospital Medicine, White and Liao³ break down the new rule, and we further discuss how this policy affects patients, hospitals, and hospitalists.

The new CMS rule requires hospitals to publish the prices of 300 “shoppable” services, including those negotiated with different payors. The rule standardizes how this information is displayed and accessed, with a daily penalty for facilities that fail to comply. Clinics and ambulatory surgical centers are currently excluded, as are facility and ancillary fees, such as those billed by pathology or anesthesiology. As White and Liao point out, a limitation for hospitalists is that this rule will only affect orders for the outpatient setting at discharge. In addition, this rule separates cost from quality. Although quality data are publicly available via CMS, price data are posted directly by hospitals, making a true value assessment difficult. To strengthen the rule, White and Liao recommend the following: increasing the financial penalty for noncompliance; aggregating data centrally to allow for comparisons; adding quality data to cost; expanding included sites and types of services; and adding common additional fees to the service price.

The larger question is whether patients will use these data in the manner intended. Previous studies have found a paradoxical relationship between patients’ expressed desire to compare prices for medical services vs documented low levels of price-shopping behavior. Mehrotra et al¹ found that lack of access to data as well as loyalty to providers were significant barriers to using price data effectively. The CMS rule increases access to the price information patients desire but cannot find. However, it is unclear whether available prices will be sufficient to change behaviors given that, aside from those with no insurance and those with high-deductible plans, most patients are fairly removed from the actual cost of service.

This rule may have a larger, unexpected impact on hospitals and access to care. Sharing price data could increase pressure on facilities to merge with larger systems in order to obtain more favorable rates via increased negotiating power. Hospitals that serve poorer communities may not be attractive merger candidates for large systems and could be left out of the push toward consolidation. Charging higher prices for the same services could lead to hospital closures or cuts in resources, potentially exacerbating health inequities for underserved populations.

On the provider end, it is unlikely that price transparency will influence resource utilization. Mummadi et al⁴ found that displaying price information in the electronic health record did not significantly influence physician ordering behavior. For hospitalists today, the emphasis on “high-value care” is already an important consideration when utilizing healthcare resources, considering the Accreditation Council for Graduate Medical Education (ACGME) requirements for residency, restrictive insurance protocols, and guidelines such as the ACR Appropriateness Criteria and the American Board of Internal Medicine’s Choosing Wisely^® campaign. Outside of extremes, separate cost data likely will not make a difference in provider ordering practices.

Although the information from this rule may not cause dramatic practice change, it will allow us to help our patients by providing those interested in price-shopping with data. This policy represents a large step toward a more transparent healthcare system, though it may have limited impact on overall healthcare costs.

Patients in the United States continue to experience rising out-of-pocket medical costs, with little access to the price information they desire when making decisions regarding medical care.¹ The Centers for Medicare & Medicaid Services (CMS) has taken steps toward transparency by requiring hospitals to publish price information.² In this issue of the Journal of Hospital Medicine, White and Liao³ break down the new rule, and we further discuss how this policy affects patients, hospitals, and hospitalists.

The new CMS rule requires hospitals to publish the prices of 300 “shoppable” services, including those negotiated with different payors. The rule standardizes how this information is displayed and accessed, with a daily penalty for facilities that fail to comply. Clinics and ambulatory surgical centers are currently excluded, as are facility and ancillary fees, such as those billed by pathology or anesthesiology. As White and Liao point out, a limitation for hospitalists is that this rule will only affect orders for the outpatient setting at discharge. In addition, this rule separates cost from quality. Although quality data are publicly available via CMS, price data are posted directly by hospitals, making a true value assessment difficult. To strengthen the rule, White and Liao recommend the following: increasing the financial penalty for noncompliance; aggregating data centrally to allow for comparisons; adding quality data to cost; expanding included sites and types of services; and adding common additional fees to the service price.

The larger question is whether patients will use these data in the manner intended. Previous studies have found a paradoxical relationship between patients’ expressed desire to compare prices for medical services vs documented low levels of price-shopping behavior. Mehrotra et al¹ found that lack of access to data as well as loyalty to providers were significant barriers to using price data effectively. The CMS rule increases access to the price information patients desire but cannot find. However, it is unclear whether available prices will be sufficient to change behaviors given that, aside from those with no insurance and those with high-deductible plans, most patients are fairly removed from the actual cost of service.

This rule may have a larger, unexpected impact on hospitals and access to care. Sharing price data could increase pressure on facilities to merge with larger systems in order to obtain more favorable rates via increased negotiating power. Hospitals that serve poorer communities may not be attractive merger candidates for large systems and could be left out of the push toward consolidation. Charging higher prices for the same services could lead to hospital closures or cuts in resources, potentially exacerbating health inequities for underserved populations.

On the provider end, it is unlikely that price transparency will influence resource utilization. Mummadi et al⁴ found that displaying price information in the electronic health record did not significantly influence physician ordering behavior. For hospitalists today, the emphasis on “high-value care” is already an important consideration when utilizing healthcare resources, considering the Accreditation Council for Graduate Medical Education (ACGME) requirements for residency, restrictive insurance protocols, and guidelines such as the ACR Appropriateness Criteria and the American Board of Internal Medicine’s Choosing Wisely^® campaign. Outside of extremes, separate cost data likely will not make a difference in provider ordering practices.

Although the information from this rule may not cause dramatic practice change, it will allow us to help our patients by providing those interested in price-shopping with data. This policy represents a large step toward a more transparent healthcare system, though it may have limited impact on overall healthcare costs.

Patients in the United States continue to experience rising out-of-pocket medical costs, with little access to the price information they desire when making decisions regarding medical care.¹ The Centers for Medicare & Medicaid Services (CMS) has taken steps toward transparency by requiring hospitals to publish price information.² In this issue of the Journal of Hospital Medicine, White and Liao³ break down the new rule, and we further discuss how this policy affects patients, hospitals, and hospitalists.

The new CMS rule requires hospitals to publish the prices of 300 “shoppable” services, including those negotiated with different payors. The rule standardizes how this information is displayed and accessed, with a daily penalty for facilities that fail to comply. Clinics and ambulatory surgical centers are currently excluded, as are facility and ancillary fees, such as those billed by pathology or anesthesiology. As White and Liao point out, a limitation for hospitalists is that this rule will only affect orders for the outpatient setting at discharge. In addition, this rule separates cost from quality. Although quality data are publicly available via CMS, price data are posted directly by hospitals, making a true value assessment difficult. To strengthen the rule, White and Liao recommend the following: increasing the financial penalty for noncompliance; aggregating data centrally to allow for comparisons; adding quality data to cost; expanding included sites and types of services; and adding common additional fees to the service price.

The larger question is whether patients will use these data in the manner intended. Previous studies have found a paradoxical relationship between patients’ expressed desire to compare prices for medical services vs documented low levels of price-shopping behavior. Mehrotra et al¹ found that lack of access to data as well as loyalty to providers were significant barriers to using price data effectively. The CMS rule increases access to the price information patients desire but cannot find. However, it is unclear whether available prices will be sufficient to change behaviors given that, aside from those with no insurance and those with high-deductible plans, most patients are fairly removed from the actual cost of service.

This rule may have a larger, unexpected impact on hospitals and access to care. Sharing price data could increase pressure on facilities to merge with larger systems in order to obtain more favorable rates via increased negotiating power. Hospitals that serve poorer communities may not be attractive merger candidates for large systems and could be left out of the push toward consolidation. Charging higher prices for the same services could lead to hospital closures or cuts in resources, potentially exacerbating health inequities for underserved populations.

On the provider end, it is unlikely that price transparency will influence resource utilization. Mummadi et al⁴ found that displaying price information in the electronic health record did not significantly influence physician ordering behavior. For hospitalists today, the emphasis on “high-value care” is already an important consideration when utilizing healthcare resources, considering the Accreditation Council for Graduate Medical Education (ACGME) requirements for residency, restrictive insurance protocols, and guidelines such as the ACR Appropriateness Criteria and the American Board of Internal Medicine’s Choosing Wisely^® campaign. Outside of extremes, separate cost data likely will not make a difference in provider ordering practices.

Although the information from this rule may not cause dramatic practice change, it will allow us to help our patients by providing those interested in price-shopping with data. This policy represents a large step toward a more transparent healthcare system, though it may have limited impact on overall healthcare costs.

Care concordant with patient goals of care (GOC) is a central component of quality. Communication about GOC is associated with improved quality of life, reduced resource utilization, and optimized end-of-life (EOL) care. Prior literature has focused on outpatient populations, with little knowledge based on preferences elicited from patients hospitalized for serious acute illness.¹ The consequent knowledge gap relates to a dimension of practice through which hospitalists can improve patient-centered care by clarifying patient preferences for goal-directed treatments both during and following hospitalization.² Implementing interventions that optimize shared decision-making through a personalized serious- illness care plan is a high-priority research area.²

In this issue, to estimate how frequently GOC are assessed during hospitalization for serious illness and the concordance between identified goals and postdischarge care, Taylor et al³ retrospectively evaluated a cohort of sepsis survivors through electronic health record (EHR) review. A standardized EHR care alignment tool and a comprehensive EHR assessment demonstrated that only 19% and 40% of patients, respectively, had identifiable GOC documented. Goal-concordant care was subsequently observed among 68% of patients with identified goals, consistent with prior work demonstrating goal-concordance in this range.¹ Data on EOL care provided to decedents in an integrated health system notably showed that 89% received goal-concordant treatments.⁴ This difference may stem from clinicians’ emphasis on goal ascertainment at the EOL, a propensity reflected in the comparative characteristics of patients with goals documented in the current study’s Table.³ Investigators took advantage of unique inpatient and postdischarge clinical information from a sepsis patient sample to provide novel insights into the inadequacy of patient preference assessment and the substantial frequency of goal-discordant care resulting from insufficient attention to GOC.

This study suggests a critical need to improve practices related to identification of GOC in patients hospitalized with serious illness. After adjusting for relevant confounding characteristics, completion of a standardized EHR care alignment tool was strongly associated with receipt of goal-concordant care following discharge.³ Although this tool was only completed in 19% of patients, this finding suggests that elicitation of patient preferences is an under-addressed step in facilitating patient-centered transitions of care. In particular, the low 39% rate of goal-concordant care among patients prioritizing comfort over longevity is noteworthy, but consistent with prior literature.¹ This degree of discordance highlights provision of goal-concordant care following hospitalization as a key, yet unfulfilled, patient-centered-care quality metric.

The identified shortcomings in communication and care represent an important opportunity for hospitalists to enhance the extent to which survivors of critical illness receive care respectful of their preferences and values. Given the importance of effective discharge handoff practices in hospital medicine,² future work should address assertively incorporating GOC into transitions after serious acute illness. Enhancing communication of these goals at discharge may benefit patients at high risk of readmission and other postdischarge adverse events, particularly for patients with comfort-focused GOC.

The study is limited in its derivation from trial participants with a specific clinical syndrome in a single health system. Also, investigators’ classification of a single patient goal does not reflect the multifactorial objectives of health interventions. In addition, since patient-reported GOC discussions correlate more highly with goal-concordant care than those identified through EHRs,⁵ future work should ascertain the generalizability of the identified gaps in practice.

The findings of this study underscore the need for clinicians to promote GOC assessment and documentation during hospitalization for high-risk conditions, such as sepsis. Tracking rates of GOC elicitation and goal-concordant care following discharge should be incorporated into quality measurement systems as important patient-centered dimensions of care. Hospitalists can fill a critical void by helping to correct the deficiencies that exist in respecting the preferences of survivors of serious acute illness.

Care concordant with patient goals of care (GOC) is a central component of quality. Communication about GOC is associated with improved quality of life, reduced resource utilization, and optimized end-of-life (EOL) care. Prior literature has focused on outpatient populations, with little knowledge based on preferences elicited from patients hospitalized for serious acute illness.¹ The consequent knowledge gap relates to a dimension of practice through which hospitalists can improve patient-centered care by clarifying patient preferences for goal-directed treatments both during and following hospitalization.² Implementing interventions that optimize shared decision-making through a personalized serious- illness care plan is a high-priority research area.²

In this issue, to estimate how frequently GOC are assessed during hospitalization for serious illness and the concordance between identified goals and postdischarge care, Taylor et al³ retrospectively evaluated a cohort of sepsis survivors through electronic health record (EHR) review. A standardized EHR care alignment tool and a comprehensive EHR assessment demonstrated that only 19% and 40% of patients, respectively, had identifiable GOC documented. Goal-concordant care was subsequently observed among 68% of patients with identified goals, consistent with prior work demonstrating goal-concordance in this range.¹ Data on EOL care provided to decedents in an integrated health system notably showed that 89% received goal-concordant treatments.⁴ This difference may stem from clinicians’ emphasis on goal ascertainment at the EOL, a propensity reflected in the comparative characteristics of patients with goals documented in the current study’s Table.³ Investigators took advantage of unique inpatient and postdischarge clinical information from a sepsis patient sample to provide novel insights into the inadequacy of patient preference assessment and the substantial frequency of goal-discordant care resulting from insufficient attention to GOC.

This study suggests a critical need to improve practices related to identification of GOC in patients hospitalized with serious illness. After adjusting for relevant confounding characteristics, completion of a standardized EHR care alignment tool was strongly associated with receipt of goal-concordant care following discharge.³ Although this tool was only completed in 19% of patients, this finding suggests that elicitation of patient preferences is an under-addressed step in facilitating patient-centered transitions of care. In particular, the low 39% rate of goal-concordant care among patients prioritizing comfort over longevity is noteworthy, but consistent with prior literature.¹ This degree of discordance highlights provision of goal-concordant care following hospitalization as a key, yet unfulfilled, patient-centered-care quality metric.

The identified shortcomings in communication and care represent an important opportunity for hospitalists to enhance the extent to which survivors of critical illness receive care respectful of their preferences and values. Given the importance of effective discharge handoff practices in hospital medicine,² future work should address assertively incorporating GOC into transitions after serious acute illness. Enhancing communication of these goals at discharge may benefit patients at high risk of readmission and other postdischarge adverse events, particularly for patients with comfort-focused GOC.

The study is limited in its derivation from trial participants with a specific clinical syndrome in a single health system. Also, investigators’ classification of a single patient goal does not reflect the multifactorial objectives of health interventions. In addition, since patient-reported GOC discussions correlate more highly with goal-concordant care than those identified through EHRs,⁵ future work should ascertain the generalizability of the identified gaps in practice.

The findings of this study underscore the need for clinicians to promote GOC assessment and documentation during hospitalization for high-risk conditions, such as sepsis. Tracking rates of GOC elicitation and goal-concordant care following discharge should be incorporated into quality measurement systems as important patient-centered dimensions of care. Hospitalists can fill a critical void by helping to correct the deficiencies that exist in respecting the preferences of survivors of serious acute illness.

Care concordant with patient goals of care (GOC) is a central component of quality. Communication about GOC is associated with improved quality of life, reduced resource utilization, and optimized end-of-life (EOL) care. Prior literature has focused on outpatient populations, with little knowledge based on preferences elicited from patients hospitalized for serious acute illness.¹ The consequent knowledge gap relates to a dimension of practice through which hospitalists can improve patient-centered care by clarifying patient preferences for goal-directed treatments both during and following hospitalization.² Implementing interventions that optimize shared decision-making through a personalized serious- illness care plan is a high-priority research area.²

In this issue, to estimate how frequently GOC are assessed during hospitalization for serious illness and the concordance between identified goals and postdischarge care, Taylor et al³ retrospectively evaluated a cohort of sepsis survivors through electronic health record (EHR) review. A standardized EHR care alignment tool and a comprehensive EHR assessment demonstrated that only 19% and 40% of patients, respectively, had identifiable GOC documented. Goal-concordant care was subsequently observed among 68% of patients with identified goals, consistent with prior work demonstrating goal-concordance in this range.¹ Data on EOL care provided to decedents in an integrated health system notably showed that 89% received goal-concordant treatments.⁴ This difference may stem from clinicians’ emphasis on goal ascertainment at the EOL, a propensity reflected in the comparative characteristics of patients with goals documented in the current study’s Table.³ Investigators took advantage of unique inpatient and postdischarge clinical information from a sepsis patient sample to provide novel insights into the inadequacy of patient preference assessment and the substantial frequency of goal-discordant care resulting from insufficient attention to GOC.

This study suggests a critical need to improve practices related to identification of GOC in patients hospitalized with serious illness. After adjusting for relevant confounding characteristics, completion of a standardized EHR care alignment tool was strongly associated with receipt of goal-concordant care following discharge.³ Although this tool was only completed in 19% of patients, this finding suggests that elicitation of patient preferences is an under-addressed step in facilitating patient-centered transitions of care. In particular, the low 39% rate of goal-concordant care among patients prioritizing comfort over longevity is noteworthy, but consistent with prior literature.¹ This degree of discordance highlights provision of goal-concordant care following hospitalization as a key, yet unfulfilled, patient-centered-care quality metric.

The identified shortcomings in communication and care represent an important opportunity for hospitalists to enhance the extent to which survivors of critical illness receive care respectful of their preferences and values. Given the importance of effective discharge handoff practices in hospital medicine,² future work should address assertively incorporating GOC into transitions after serious acute illness. Enhancing communication of these goals at discharge may benefit patients at high risk of readmission and other postdischarge adverse events, particularly for patients with comfort-focused GOC.

The study is limited in its derivation from trial participants with a specific clinical syndrome in a single health system. Also, investigators’ classification of a single patient goal does not reflect the multifactorial objectives of health interventions. In addition, since patient-reported GOC discussions correlate more highly with goal-concordant care than those identified through EHRs,⁵ future work should ascertain the generalizability of the identified gaps in practice.

The findings of this study underscore the need for clinicians to promote GOC assessment and documentation during hospitalization for high-risk conditions, such as sepsis. Tracking rates of GOC elicitation and goal-concordant care following discharge should be incorporated into quality measurement systems as important patient-centered dimensions of care. Hospitalists can fill a critical void by helping to correct the deficiencies that exist in respecting the preferences of survivors of serious acute illness.

The advent of COVID-19 saw a precipitous decline in inpatient admissions. Even before the COVID-19 pandemic, hospitals were seeing a trend toward fewer inpatient admissions for Medicare beneficiaries, which has not been thoroughly examined or explained.¹ In this issue, Keohane et al² studied Medicare inpatient episode trends between 2009 and 2017 and found that, during this period, inpatient episodes per 1000 Medicare fee-for-service (FFS) beneficiaries declined by 18.2%, from 326 to 267 per 1000 beneficiaries.

This trend can be partly explained by changes in the way that care is delivered. First, observation stays have risen, and these are excluded in the authors’ analysis. From 2010 to 2017, observation visits per 1000 beneficiaries increased from 28 to 51.¹ Second, due to improved outpatient management, margin constraints, and efficiency gains, hospitals are less likely to admit patients with less complex problems or keep patients overnight for uncomplicated procedural interventions. In cardiology, there has been an increase in the proportion of same-day percutaneous coronary interventions, from 4.5% in 2009 to 28.6% in 2017.³ The authors do not include a quantitative measure of complexity, but their data support this conclusion as they find larger declines in episodes that began with a planned admission and those that involved no use of post–acute care services, and thus were likely less complicated admissions. Finally, the increased use of alternative care sites such as home-based care settings and urgent care clinics, the proliferation of telemedicine, and the continual development of guideline-based therapy have resulted in better outpatient management of diseases.

The growth of value-based care has also contributed to the reduction in inpatient admission. The past decade has seen the growth of bundled-payment contracts, accountable care organizations (ACO), and advanced primary care models. In 2018, an estimated 20% of Medicare beneficiaries were part of an ACO.⁴ These changes have led healthcare systems to invest in care management and postdischarge interventions, such as postdischarge phone calls, transitional clinics, and transition guides to reduce admissions and readmissions. Johns Hopkins adopted all these strategies to drive performance on the Maryland Total Cost of Care Model, which like an ACO holds hospitals accountable for both inpatient and outpatient costs incurred by Medicare FFS beneficiaries. A consistent theme among successful ACOs has been a reduction in inpatient spending.⁵

The authors are likely undercounting the volume of admissions by Medicare beneficiaries. First, to define an episode, they leverage the Medicare definition of bundles and include traditional Medicare inpatient, outpatient, and Part D services 30 days prior to hospitalizations and up to 90 days after. Admissions for the same diagnosis related group that occur in the 90 days after the anchor hospitalization are included in the same episode. From a clinical perspective, it is not intuitively clear why an admission for heart failure or pneumonia that occurs 3 months after an anchor hospitalization would not be defined as a separate and distinct admission rather than a readmission. Second, their analysis focuses on Medicare FFS and does not include Medicare Advantage, which now accounts for 42% of total Medicare beneficiaries. In fact, Medicare Advantage experienced significant growth in enrollment during the study period, increasing from 10 million to 24 million beneficiaries.⁶

Despite the reduction in inpatient volumes, the authors find that inpatient spending has increased. Spending per episode increased by 11.4% over this period, when adjusted for Medicare payment increases. Actual spending per episode unadjusted for payment increases rose by 25%. Thus, they astutely point out that most of the increase has been driven by Medicare payment increases. It is likely that increases in the complexity of patients and more dedicated focus on appropriate coding have also contributed. The authors, however, do not provide information on changes to the total cost of care outside of their defined inpatient episodes, a relevant measure to those participating in value-based models.

It is likely that the trend toward fewer inpatient admissions and increased outpatient management of medical conditions will continue as value-based care models grow. Studies like these are important in documenting this trend, but it will be important in future studies to understand how these changes have impacted the quality of care delivered to patients. Prior studies have found that reductions in readmissions through the Hospital Readmission Reduction Program were associated with increases in mortality as a potential unintended consequence.⁷

The advent of COVID-19 saw a precipitous decline in inpatient admissions. Even before the COVID-19 pandemic, hospitals were seeing a trend toward fewer inpatient admissions for Medicare beneficiaries, which has not been thoroughly examined or explained.¹ In this issue, Keohane et al² studied Medicare inpatient episode trends between 2009 and 2017 and found that, during this period, inpatient episodes per 1000 Medicare fee-for-service (FFS) beneficiaries declined by 18.2%, from 326 to 267 per 1000 beneficiaries.

This trend can be partly explained by changes in the way that care is delivered. First, observation stays have risen, and these are excluded in the authors’ analysis. From 2010 to 2017, observation visits per 1000 beneficiaries increased from 28 to 51.¹ Second, due to improved outpatient management, margin constraints, and efficiency gains, hospitals are less likely to admit patients with less complex problems or keep patients overnight for uncomplicated procedural interventions. In cardiology, there has been an increase in the proportion of same-day percutaneous coronary interventions, from 4.5% in 2009 to 28.6% in 2017.³ The authors do not include a quantitative measure of complexity, but their data support this conclusion as they find larger declines in episodes that began with a planned admission and those that involved no use of post–acute care services, and thus were likely less complicated admissions. Finally, the increased use of alternative care sites such as home-based care settings and urgent care clinics, the proliferation of telemedicine, and the continual development of guideline-based therapy have resulted in better outpatient management of diseases.

The growth of value-based care has also contributed to the reduction in inpatient admission. The past decade has seen the growth of bundled-payment contracts, accountable care organizations (ACO), and advanced primary care models. In 2018, an estimated 20% of Medicare beneficiaries were part of an ACO.⁴ These changes have led healthcare systems to invest in care management and postdischarge interventions, such as postdischarge phone calls, transitional clinics, and transition guides to reduce admissions and readmissions. Johns Hopkins adopted all these strategies to drive performance on the Maryland Total Cost of Care Model, which like an ACO holds hospitals accountable for both inpatient and outpatient costs incurred by Medicare FFS beneficiaries. A consistent theme among successful ACOs has been a reduction in inpatient spending.⁵

The authors are likely undercounting the volume of admissions by Medicare beneficiaries. First, to define an episode, they leverage the Medicare definition of bundles and include traditional Medicare inpatient, outpatient, and Part D services 30 days prior to hospitalizations and up to 90 days after. Admissions for the same diagnosis related group that occur in the 90 days after the anchor hospitalization are included in the same episode. From a clinical perspective, it is not intuitively clear why an admission for heart failure or pneumonia that occurs 3 months after an anchor hospitalization would not be defined as a separate and distinct admission rather than a readmission. Second, their analysis focuses on Medicare FFS and does not include Medicare Advantage, which now accounts for 42% of total Medicare beneficiaries. In fact, Medicare Advantage experienced significant growth in enrollment during the study period, increasing from 10 million to 24 million beneficiaries.⁶

Despite the reduction in inpatient volumes, the authors find that inpatient spending has increased. Spending per episode increased by 11.4% over this period, when adjusted for Medicare payment increases. Actual spending per episode unadjusted for payment increases rose by 25%. Thus, they astutely point out that most of the increase has been driven by Medicare payment increases. It is likely that increases in the complexity of patients and more dedicated focus on appropriate coding have also contributed. The authors, however, do not provide information on changes to the total cost of care outside of their defined inpatient episodes, a relevant measure to those participating in value-based models.

It is likely that the trend toward fewer inpatient admissions and increased outpatient management of medical conditions will continue as value-based care models grow. Studies like these are important in documenting this trend, but it will be important in future studies to understand how these changes have impacted the quality of care delivered to patients. Prior studies have found that reductions in readmissions through the Hospital Readmission Reduction Program were associated with increases in mortality as a potential unintended consequence.⁷

The advent of COVID-19 saw a precipitous decline in inpatient admissions. Even before the COVID-19 pandemic, hospitals were seeing a trend toward fewer inpatient admissions for Medicare beneficiaries, which has not been thoroughly examined or explained.¹ In this issue, Keohane et al² studied Medicare inpatient episode trends between 2009 and 2017 and found that, during this period, inpatient episodes per 1000 Medicare fee-for-service (FFS) beneficiaries declined by 18.2%, from 326 to 267 per 1000 beneficiaries.

This trend can be partly explained by changes in the way that care is delivered. First, observation stays have risen, and these are excluded in the authors’ analysis. From 2010 to 2017, observation visits per 1000 beneficiaries increased from 28 to 51.¹ Second, due to improved outpatient management, margin constraints, and efficiency gains, hospitals are less likely to admit patients with less complex problems or keep patients overnight for uncomplicated procedural interventions. In cardiology, there has been an increase in the proportion of same-day percutaneous coronary interventions, from 4.5% in 2009 to 28.6% in 2017.³ The authors do not include a quantitative measure of complexity, but their data support this conclusion as they find larger declines in episodes that began with a planned admission and those that involved no use of post–acute care services, and thus were likely less complicated admissions. Finally, the increased use of alternative care sites such as home-based care settings and urgent care clinics, the proliferation of telemedicine, and the continual development of guideline-based therapy have resulted in better outpatient management of diseases.

The growth of value-based care has also contributed to the reduction in inpatient admission. The past decade has seen the growth of bundled-payment contracts, accountable care organizations (ACO), and advanced primary care models. In 2018, an estimated 20% of Medicare beneficiaries were part of an ACO.⁴ These changes have led healthcare systems to invest in care management and postdischarge interventions, such as postdischarge phone calls, transitional clinics, and transition guides to reduce admissions and readmissions. Johns Hopkins adopted all these strategies to drive performance on the Maryland Total Cost of Care Model, which like an ACO holds hospitals accountable for both inpatient and outpatient costs incurred by Medicare FFS beneficiaries. A consistent theme among successful ACOs has been a reduction in inpatient spending.⁵

The authors are likely undercounting the volume of admissions by Medicare beneficiaries. First, to define an episode, they leverage the Medicare definition of bundles and include traditional Medicare inpatient, outpatient, and Part D services 30 days prior to hospitalizations and up to 90 days after. Admissions for the same diagnosis related group that occur in the 90 days after the anchor hospitalization are included in the same episode. From a clinical perspective, it is not intuitively clear why an admission for heart failure or pneumonia that occurs 3 months after an anchor hospitalization would not be defined as a separate and distinct admission rather than a readmission. Second, their analysis focuses on Medicare FFS and does not include Medicare Advantage, which now accounts for 42% of total Medicare beneficiaries. In fact, Medicare Advantage experienced significant growth in enrollment during the study period, increasing from 10 million to 24 million beneficiaries.⁶

Despite the reduction in inpatient volumes, the authors find that inpatient spending has increased. Spending per episode increased by 11.4% over this period, when adjusted for Medicare payment increases. Actual spending per episode unadjusted for payment increases rose by 25%. Thus, they astutely point out that most of the increase has been driven by Medicare payment increases. It is likely that increases in the complexity of patients and more dedicated focus on appropriate coding have also contributed. The authors, however, do not provide information on changes to the total cost of care outside of their defined inpatient episodes, a relevant measure to those participating in value-based models.

It is likely that the trend toward fewer inpatient admissions and increased outpatient management of medical conditions will continue as value-based care models grow. Studies like these are important in documenting this trend, but it will be important in future studies to understand how these changes have impacted the quality of care delivered to patients. Prior studies have found that reductions in readmissions through the Hospital Readmission Reduction Program were associated with increases in mortality as a potential unintended consequence.⁷

Two children who presented to emergency departments in different cities were diagnosed with diabetes mellitus and ketoacidosis. On presentation, both had significant anion gap metabolic acidosis. Because the patients were deemed unsafe for discharge, the admitting physician placed orders that dictated hospital care, including an order that designated the stay as observation (OBS) or inpatient (IP) status. During their stay, both patients received care including continuous infusion of insulin, intravenous fluids, and frequent lab monitoring. Each child recovered quickly and was discharged in less than 48 hours.

Despite both patients receiving comparable care, recovering well, and being discharged home after a similar length of stay, their encounter designation may be different. Although the patient outcome is of utmost importance, the consequences of labeling an encounter as OBS or IP status are complex and may impact the financial standing of patients, hospitals, and payors. Determining the trajectory of OBS status and its utilization in the pediatric population is vital to understanding the consequences of this designation.

In this issue of the Journal of Hospital Medicine, Tian et al¹ describe the increase in OBS status hospitalizations between 2010 and 2019, with OBS stays accounting for approximately one-third of pediatric hospitalizations within children’s hospitals in 2019. The increase in OBS status use was described in 19 of 20 of the most common All Patient Refined Diagnosis Related Groups, with the highest growth noted for surgical conditions and diabetes mellitus.¹ These frequently seen, high-stakes conditions, when expertly managed, may result in a safe discharge within 48 hours of admission, but the labor-intensive technical skills to ensure patient safety and high-value care often differ greatly from the idea of simply “observing” a patient.

The scope creep of OBS status in pediatrics is evident. OBS status was initially designed to acknowledge a prolonged outpatient period of monitoring with a goal of determining whether inpatient hospitalization was warranted. However, in most circumstances, the care of children under OBS status differs little from those under IP status; OBS status patients are usually cared for in the same wards and by the same providers as IP status patients. The similarities in care lead to nearly equivalent hospital costs for IP and OBS stays.² Comparable hospital costs would be less concerning if reimbursement were proportional, but OBS status hospitalizations are reimbursed at lower outpatient rates.³ The combination of similar costs and lower reimbursement results in a financial liability for children’s hospitals.

Tian et al add to the growing body of literature that underscores concerns with OBS stays.¹ Its increasing use over the past decade represents a troubling continuation of increased OBS status use described by Macy et al³ nearly a decade ago, and the variability with which it is applied suggests that the designation has little connection to the clinical status of patients. Instead, its use is more likely influenced by local payor contracts, individual state laws, and provider culture. For individual institutions, this differential application affects more than just reimbursement. OBS stays are often excluded from nationally representative administrative databases, which makes hospital benchmarking, research on outcomes, and accurate comparison of patient populations impossible.^4,5

The trends described by Tian et al¹ raise concerns about the potential impact that OBS stays have on patients and hospital systems across the country. OBS status was created to serve a clinical need, but its inconsistent use places hospitals and the children they treat at risk. This erratic application of OBS status and the serious results of its assignment to pediatric hospitalizations provide evidence that criteria for OBS need to be standardized or otherwise abandoned outright.

Two children who presented to emergency departments in different cities were diagnosed with diabetes mellitus and ketoacidosis. On presentation, both had significant anion gap metabolic acidosis. Because the patients were deemed unsafe for discharge, the admitting physician placed orders that dictated hospital care, including an order that designated the stay as observation (OBS) or inpatient (IP) status. During their stay, both patients received care including continuous infusion of insulin, intravenous fluids, and frequent lab monitoring. Each child recovered quickly and was discharged in less than 48 hours.

Despite both patients receiving comparable care, recovering well, and being discharged home after a similar length of stay, their encounter designation may be different. Although the patient outcome is of utmost importance, the consequences of labeling an encounter as OBS or IP status are complex and may impact the financial standing of patients, hospitals, and payors. Determining the trajectory of OBS status and its utilization in the pediatric population is vital to understanding the consequences of this designation.

In this issue of the Journal of Hospital Medicine, Tian et al¹ describe the increase in OBS status hospitalizations between 2010 and 2019, with OBS stays accounting for approximately one-third of pediatric hospitalizations within children’s hospitals in 2019. The increase in OBS status use was described in 19 of 20 of the most common All Patient Refined Diagnosis Related Groups, with the highest growth noted for surgical conditions and diabetes mellitus.¹ These frequently seen, high-stakes conditions, when expertly managed, may result in a safe discharge within 48 hours of admission, but the labor-intensive technical skills to ensure patient safety and high-value care often differ greatly from the idea of simply “observing” a patient.

The scope creep of OBS status in pediatrics is evident. OBS status was initially designed to acknowledge a prolonged outpatient period of monitoring with a goal of determining whether inpatient hospitalization was warranted. However, in most circumstances, the care of children under OBS status differs little from those under IP status; OBS status patients are usually cared for in the same wards and by the same providers as IP status patients. The similarities in care lead to nearly equivalent hospital costs for IP and OBS stays.² Comparable hospital costs would be less concerning if reimbursement were proportional, but OBS status hospitalizations are reimbursed at lower outpatient rates.³ The combination of similar costs and lower reimbursement results in a financial liability for children’s hospitals.

Tian et al add to the growing body of literature that underscores concerns with OBS stays.¹ Its increasing use over the past decade represents a troubling continuation of increased OBS status use described by Macy et al³ nearly a decade ago, and the variability with which it is applied suggests that the designation has little connection to the clinical status of patients. Instead, its use is more likely influenced by local payor contracts, individual state laws, and provider culture. For individual institutions, this differential application affects more than just reimbursement. OBS stays are often excluded from nationally representative administrative databases, which makes hospital benchmarking, research on outcomes, and accurate comparison of patient populations impossible.^4,5

The trends described by Tian et al¹ raise concerns about the potential impact that OBS stays have on patients and hospital systems across the country. OBS status was created to serve a clinical need, but its inconsistent use places hospitals and the children they treat at risk. This erratic application of OBS status and the serious results of its assignment to pediatric hospitalizations provide evidence that criteria for OBS need to be standardized or otherwise abandoned outright.

Two children who presented to emergency departments in different cities were diagnosed with diabetes mellitus and ketoacidosis. On presentation, both had significant anion gap metabolic acidosis. Because the patients were deemed unsafe for discharge, the admitting physician placed orders that dictated hospital care, including an order that designated the stay as observation (OBS) or inpatient (IP) status. During their stay, both patients received care including continuous infusion of insulin, intravenous fluids, and frequent lab monitoring. Each child recovered quickly and was discharged in less than 48 hours.

Despite both patients receiving comparable care, recovering well, and being discharged home after a similar length of stay, their encounter designation may be different. Although the patient outcome is of utmost importance, the consequences of labeling an encounter as OBS or IP status are complex and may impact the financial standing of patients, hospitals, and payors. Determining the trajectory of OBS status and its utilization in the pediatric population is vital to understanding the consequences of this designation.

In this issue of the Journal of Hospital Medicine, Tian et al¹ describe the increase in OBS status hospitalizations between 2010 and 2019, with OBS stays accounting for approximately one-third of pediatric hospitalizations within children’s hospitals in 2019. The increase in OBS status use was described in 19 of 20 of the most common All Patient Refined Diagnosis Related Groups, with the highest growth noted for surgical conditions and diabetes mellitus.¹ These frequently seen, high-stakes conditions, when expertly managed, may result in a safe discharge within 48 hours of admission, but the labor-intensive technical skills to ensure patient safety and high-value care often differ greatly from the idea of simply “observing” a patient.

The scope creep of OBS status in pediatrics is evident. OBS status was initially designed to acknowledge a prolonged outpatient period of monitoring with a goal of determining whether inpatient hospitalization was warranted. However, in most circumstances, the care of children under OBS status differs little from those under IP status; OBS status patients are usually cared for in the same wards and by the same providers as IP status patients. The similarities in care lead to nearly equivalent hospital costs for IP and OBS stays.² Comparable hospital costs would be less concerning if reimbursement were proportional, but OBS status hospitalizations are reimbursed at lower outpatient rates.³ The combination of similar costs and lower reimbursement results in a financial liability for children’s hospitals.

Tian et al add to the growing body of literature that underscores concerns with OBS stays.¹ Its increasing use over the past decade represents a troubling continuation of increased OBS status use described by Macy et al³ nearly a decade ago, and the variability with which it is applied suggests that the designation has little connection to the clinical status of patients. Instead, its use is more likely influenced by local payor contracts, individual state laws, and provider culture. For individual institutions, this differential application affects more than just reimbursement. OBS stays are often excluded from nationally representative administrative databases, which makes hospital benchmarking, research on outcomes, and accurate comparison of patient populations impossible.^4,5

The trends described by Tian et al¹ raise concerns about the potential impact that OBS stays have on patients and hospital systems across the country. OBS status was created to serve a clinical need, but its inconsistent use places hospitals and the children they treat at risk. This erratic application of OBS status and the serious results of its assignment to pediatric hospitalizations provide evidence that criteria for OBS need to be standardized or otherwise abandoned outright.