Another study caught my attention this month for having presented a lot of information with no clinically important conclusions. In "Mode of Delivery and Offspring Atopic Dermatitis in a Swedish Nationwide Study," Mubanga and colleagues studied 1.4 million children! With that many participants, they were almost certain to find associations that were statistically significant and clinically irrelevant. They reported that children born by instrumental vaginal delivery, emergency caesarean section, and elective caesarean section were at a higher risk for AD compared with those born by uncomplicated vaginal delivery. They failed to report the absolute magnitude of the associations, which were undoubtedly so small as to be clinically meaningless. Even if the observed association were not due to some hidden bias, the association is not anything that would change treatment in any way.

On the other hand, the small, open label registry analysis, "Experiences From Daily Practice of Upadacitinib Treatment on Atopic Dermatitis With a Focus on Hand Eczema: Results From the BioDay Registry," published by Kamphuis and colleagues, is of much greater value, reporting the effectiveness and safety of upadacitinib on hand eczema. Not surprisingly, there were large improvements in the investigators' assessments of the dermatitis and in patients' quality of life. This small study is informative about efficacy; it is too small, though, to evaluate how frequently rare severe adverse events occur.

The use of probiotics to safely improve skin disease is such an appealing concept, yet it sounds a lot like hocus-pocus to me. Feíto-Rodríguez and colleagues report in the journal Clinical and Experimental Dermatology that a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum, and Lactobacillus casei improved atopic dermatitis more than did placebo. The findings are not compelling. Differences were small. Rates of being clear or almost clear weren't reported. We can get atopic dermatitis to clear up in a few days with topical triamcinolone (if we can get patients to use it); so far, the effects of probiotics on the presumed gut-immune system-skin axis seem very much underwhelming.

Another study caught my attention this month for having presented a lot of information with no clinically important conclusions. In "Mode of Delivery and Offspring Atopic Dermatitis in a Swedish Nationwide Study," Mubanga and colleagues studied 1.4 million children! With that many participants, they were almost certain to find associations that were statistically significant and clinically irrelevant. They reported that children born by instrumental vaginal delivery, emergency caesarean section, and elective caesarean section were at a higher risk for AD compared with those born by uncomplicated vaginal delivery. They failed to report the absolute magnitude of the associations, which were undoubtedly so small as to be clinically meaningless. Even if the observed association were not due to some hidden bias, the association is not anything that would change treatment in any way.

On the other hand, the small, open label registry analysis, "Experiences From Daily Practice of Upadacitinib Treatment on Atopic Dermatitis With a Focus on Hand Eczema: Results From the BioDay Registry," published by Kamphuis and colleagues, is of much greater value, reporting the effectiveness and safety of upadacitinib on hand eczema. Not surprisingly, there were large improvements in the investigators' assessments of the dermatitis and in patients' quality of life. This small study is informative about efficacy; it is too small, though, to evaluate how frequently rare severe adverse events occur.

The use of probiotics to safely improve skin disease is such an appealing concept, yet it sounds a lot like hocus-pocus to me. Feíto-Rodríguez and colleagues report in the journal Clinical and Experimental Dermatology that a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum, and Lactobacillus casei improved atopic dermatitis more than did placebo. The findings are not compelling. Differences were small. Rates of being clear or almost clear weren't reported. We can get atopic dermatitis to clear up in a few days with topical triamcinolone (if we can get patients to use it); so far, the effects of probiotics on the presumed gut-immune system-skin axis seem very much underwhelming.

Another study caught my attention this month for having presented a lot of information with no clinically important conclusions. In "Mode of Delivery and Offspring Atopic Dermatitis in a Swedish Nationwide Study," Mubanga and colleagues studied 1.4 million children! With that many participants, they were almost certain to find associations that were statistically significant and clinically irrelevant. They reported that children born by instrumental vaginal delivery, emergency caesarean section, and elective caesarean section were at a higher risk for AD compared with those born by uncomplicated vaginal delivery. They failed to report the absolute magnitude of the associations, which were undoubtedly so small as to be clinically meaningless. Even if the observed association were not due to some hidden bias, the association is not anything that would change treatment in any way.

On the other hand, the small, open label registry analysis, "Experiences From Daily Practice of Upadacitinib Treatment on Atopic Dermatitis With a Focus on Hand Eczema: Results From the BioDay Registry," published by Kamphuis and colleagues, is of much greater value, reporting the effectiveness and safety of upadacitinib on hand eczema. Not surprisingly, there were large improvements in the investigators' assessments of the dermatitis and in patients' quality of life. This small study is informative about efficacy; it is too small, though, to evaluate how frequently rare severe adverse events occur.

The use of probiotics to safely improve skin disease is such an appealing concept, yet it sounds a lot like hocus-pocus to me. Feíto-Rodríguez and colleagues report in the journal Clinical and Experimental Dermatology that a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum, and Lactobacillus casei improved atopic dermatitis more than did placebo. The findings are not compelling. Differences were small. Rates of being clear or almost clear weren't reported. We can get atopic dermatitis to clear up in a few days with topical triamcinolone (if we can get patients to use it); so far, the effects of probiotics on the presumed gut-immune system-skin axis seem very much underwhelming.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. This is based on an interview, Back Pain Update with Dr. Austin Baraki. He gave us some great pearls about how to manage back pain, which we see so much of in primary care. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?

Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.

Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.

We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
 

Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.

Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.

First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.

The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.

The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
 

Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.

Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.

This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
 

Dr. Williams: And I’m Dr. Paul Nelson Williams.

Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.

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

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at the University of Oxford. I’d like to talk to you today about something specific and generic around guidelines.

Annals of Oncology, my old journal, has just published an outstanding set of guidelines delivered by the ESMO (European Society for Medical Oncology) guidelines group. It’s around the management of toxicities from immunotherapy, and it’s the ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up, delivered by Dr. Haanen and, of course, a number of colleagues on behalf of the wider committee.

Have a look at it. I’m not going to talk about the details of it. It’s very well written. It’s very clear and evidence based, of course. There are many helpful hints and a very clear blueprint as to how we should better manage the myriad of potential side effects from immunotherapy.

It tells us a little about the basis of the science, some of the mechanistic work that’s going on in allowing us to understand why some people react in such different ways, almost as if the immune systems are primed to overreact. It gives a very helpful, stepwise look at how we best diagnose, manage, and, in the longer term, follow up patients who have problems with these very important drugs.

All of us recognize the extraordinary impact they’ve made across a wide range of different tumor types, and therefore, as practicing oncologists and health care professionals in the field, all of us need to understand better the details as to how we better care for our patients on these drugs.

Have a look at it. It’s well written and useful, and I think it’s a document that I’ll turn to when I’m looking for a refresher or advice in the future.

The generic focus is about guidelines. Many years ago, I was one of the architects of the British National Cancer Plan, and for me, there were four simple principles at that stage in our development of how we would improve the delivery of cancer control in the United Kingdom. It was around site specialization, particularly of our surgical colleagues who embraced this with vigor. God bless them.

It was using guidelines to help level up the quality of treatment that we were giving, of course underpinned by research, and using – one would hope – modern IT and telecommunications to improve the networking that we use to deliver multidisciplinary cancer care, one of the key elements. Guidelines were embedded in that.

A couple of years ago, we did a survey of cancer physicians around the world. Almost 30 different countries were represented, and we asked which guidelines were most used. It was a very interesting set of responses. The three dominant guidelines – this will surprise no one – are the NCCN (National Comprehensive Cancer Network) guidelines, the ESMO guidelines, and the ASCO (American Society of Clinical Oncology) guidelines.

Rather than selecting one and one being completely dominant, what seemed to be the case is that our colleagues around the world dipped in and used all three. They may prefer NCCN for some particular tumor type or some particular aspect of how they’re structured, but at the same time, we would dip into the ESMO guidelines for specific bits of help, as well as the ASCO guidelines.

I find this fascinating. I assume that in different regions, depending on how they were affiliated in terms of additional training or links to Europe or links to the United States, that one or other of these guideline groups would predominate, but no. In each country, in each region, given the large data bank that we have of guidelines now, it’s a sort of pick-and-mix situation.

I was initially surprised but then took comfort from it. There’s nothing I hate more than the wasted energy of reduplication and saying, well come on, if there is one guideline set that does truly command the attention of the world, then the other should stop. It’s wasted energy, which is something that none of us can afford.

The fact that each of these trusted, evidence-based, beautifully presented guidelines is used in different ways was important. A message to the guideline groups from me is: “Thank you for your professionalism, for the hard work of hundreds of cancer specialists from all different specialties, and for their contribution to developing these guidelines.”

It’s worth it, it’s working, people are using them, and they’re making a difference. It’s all about leveling up the quality of cancer care that we deliver.

Specifically, have a look at the ESMO immune guidelines. They are great. I hope you find them helpful. Generically, thanks to all of you who are contributing and working so hard to make these data available to improve the quality of cancer care around the world.

Thanks for listening, as always. I’m interested in any comments that you might have, but for the time being, Medscapers, ahoy.

David J. Kerr, CBE, MD, DSc, is a professor of cancer medicine at the University of Oxford. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, and Merck Serono.

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

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at the University of Oxford. I’d like to talk to you today about something specific and generic around guidelines.

Annals of Oncology, my old journal, has just published an outstanding set of guidelines delivered by the ESMO (European Society for Medical Oncology) guidelines group. It’s around the management of toxicities from immunotherapy, and it’s the ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up, delivered by Dr. Haanen and, of course, a number of colleagues on behalf of the wider committee.

Have a look at it. I’m not going to talk about the details of it. It’s very well written. It’s very clear and evidence based, of course. There are many helpful hints and a very clear blueprint as to how we should better manage the myriad of potential side effects from immunotherapy.

It tells us a little about the basis of the science, some of the mechanistic work that’s going on in allowing us to understand why some people react in such different ways, almost as if the immune systems are primed to overreact. It gives a very helpful, stepwise look at how we best diagnose, manage, and, in the longer term, follow up patients who have problems with these very important drugs.

All of us recognize the extraordinary impact they’ve made across a wide range of different tumor types, and therefore, as practicing oncologists and health care professionals in the field, all of us need to understand better the details as to how we better care for our patients on these drugs.

Have a look at it. It’s well written and useful, and I think it’s a document that I’ll turn to when I’m looking for a refresher or advice in the future.

The generic focus is about guidelines. Many years ago, I was one of the architects of the British National Cancer Plan, and for me, there were four simple principles at that stage in our development of how we would improve the delivery of cancer control in the United Kingdom. It was around site specialization, particularly of our surgical colleagues who embraced this with vigor. God bless them.

It was using guidelines to help level up the quality of treatment that we were giving, of course underpinned by research, and using – one would hope – modern IT and telecommunications to improve the networking that we use to deliver multidisciplinary cancer care, one of the key elements. Guidelines were embedded in that.

A couple of years ago, we did a survey of cancer physicians around the world. Almost 30 different countries were represented, and we asked which guidelines were most used. It was a very interesting set of responses. The three dominant guidelines – this will surprise no one – are the NCCN (National Comprehensive Cancer Network) guidelines, the ESMO guidelines, and the ASCO (American Society of Clinical Oncology) guidelines.

Rather than selecting one and one being completely dominant, what seemed to be the case is that our colleagues around the world dipped in and used all three. They may prefer NCCN for some particular tumor type or some particular aspect of how they’re structured, but at the same time, we would dip into the ESMO guidelines for specific bits of help, as well as the ASCO guidelines.

I find this fascinating. I assume that in different regions, depending on how they were affiliated in terms of additional training or links to Europe or links to the United States, that one or other of these guideline groups would predominate, but no. In each country, in each region, given the large data bank that we have of guidelines now, it’s a sort of pick-and-mix situation.

I was initially surprised but then took comfort from it. There’s nothing I hate more than the wasted energy of reduplication and saying, well come on, if there is one guideline set that does truly command the attention of the world, then the other should stop. It’s wasted energy, which is something that none of us can afford.

The fact that each of these trusted, evidence-based, beautifully presented guidelines is used in different ways was important. A message to the guideline groups from me is: “Thank you for your professionalism, for the hard work of hundreds of cancer specialists from all different specialties, and for their contribution to developing these guidelines.”

It’s worth it, it’s working, people are using them, and they’re making a difference. It’s all about leveling up the quality of cancer care that we deliver.

Specifically, have a look at the ESMO immune guidelines. They are great. I hope you find them helpful. Generically, thanks to all of you who are contributing and working so hard to make these data available to improve the quality of cancer care around the world.

Thanks for listening, as always. I’m interested in any comments that you might have, but for the time being, Medscapers, ahoy.

David J. Kerr, CBE, MD, DSc, is a professor of cancer medicine at the University of Oxford. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, and Merck Serono.

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

This transcript has been edited for clarity.

I’m David Kerr, professor of cancer medicine at the University of Oxford. I’d like to talk to you today about something specific and generic around guidelines.

Annals of Oncology, my old journal, has just published an outstanding set of guidelines delivered by the ESMO (European Society for Medical Oncology) guidelines group. It’s around the management of toxicities from immunotherapy, and it’s the ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up, delivered by Dr. Haanen and, of course, a number of colleagues on behalf of the wider committee.

Have a look at it. I’m not going to talk about the details of it. It’s very well written. It’s very clear and evidence based, of course. There are many helpful hints and a very clear blueprint as to how we should better manage the myriad of potential side effects from immunotherapy.

It tells us a little about the basis of the science, some of the mechanistic work that’s going on in allowing us to understand why some people react in such different ways, almost as if the immune systems are primed to overreact. It gives a very helpful, stepwise look at how we best diagnose, manage, and, in the longer term, follow up patients who have problems with these very important drugs.

All of us recognize the extraordinary impact they’ve made across a wide range of different tumor types, and therefore, as practicing oncologists and health care professionals in the field, all of us need to understand better the details as to how we better care for our patients on these drugs.

Have a look at it. It’s well written and useful, and I think it’s a document that I’ll turn to when I’m looking for a refresher or advice in the future.

The generic focus is about guidelines. Many years ago, I was one of the architects of the British National Cancer Plan, and for me, there were four simple principles at that stage in our development of how we would improve the delivery of cancer control in the United Kingdom. It was around site specialization, particularly of our surgical colleagues who embraced this with vigor. God bless them.

It was using guidelines to help level up the quality of treatment that we were giving, of course underpinned by research, and using – one would hope – modern IT and telecommunications to improve the networking that we use to deliver multidisciplinary cancer care, one of the key elements. Guidelines were embedded in that.

A couple of years ago, we did a survey of cancer physicians around the world. Almost 30 different countries were represented, and we asked which guidelines were most used. It was a very interesting set of responses. The three dominant guidelines – this will surprise no one – are the NCCN (National Comprehensive Cancer Network) guidelines, the ESMO guidelines, and the ASCO (American Society of Clinical Oncology) guidelines.

Rather than selecting one and one being completely dominant, what seemed to be the case is that our colleagues around the world dipped in and used all three. They may prefer NCCN for some particular tumor type or some particular aspect of how they’re structured, but at the same time, we would dip into the ESMO guidelines for specific bits of help, as well as the ASCO guidelines.

I find this fascinating. I assume that in different regions, depending on how they were affiliated in terms of additional training or links to Europe or links to the United States, that one or other of these guideline groups would predominate, but no. In each country, in each region, given the large data bank that we have of guidelines now, it’s a sort of pick-and-mix situation.

I was initially surprised but then took comfort from it. There’s nothing I hate more than the wasted energy of reduplication and saying, well come on, if there is one guideline set that does truly command the attention of the world, then the other should stop. It’s wasted energy, which is something that none of us can afford.

The fact that each of these trusted, evidence-based, beautifully presented guidelines is used in different ways was important. A message to the guideline groups from me is: “Thank you for your professionalism, for the hard work of hundreds of cancer specialists from all different specialties, and for their contribution to developing these guidelines.”

It’s worth it, it’s working, people are using them, and they’re making a difference. It’s all about leveling up the quality of cancer care that we deliver.

Specifically, have a look at the ESMO immune guidelines. They are great. I hope you find them helpful. Generically, thanks to all of you who are contributing and working so hard to make these data available to improve the quality of cancer care around the world.

Thanks for listening, as always. I’m interested in any comments that you might have, but for the time being, Medscapers, ahoy.

David J. Kerr, CBE, MD, DSc, is a professor of cancer medicine at the University of Oxford. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, and Merck Serono.

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

No significant differences emerged in gut microbial diversity in preterm infants who exclusively received human milk products, compared with those receiving bovine milk formula or fortifiers, a randomized controlled trial found. Nor were any differences noted in the secondary endpoint of clinical outcomes in the U.K. study, published online in JAMA Network Open.

Newcastle University

The finding was unanticipated, according to lead author Nicholas D. Embleton, MBBS, MD, a professor of neonatal medicine at Newcastle University in England. “Over the last 10 years we’ve focused particularly on the role of the microbiome to better understand causal mechanisms of necrotizing enterocolitis, or NEC,” he said in an interview. “We anticipated that an exclusive human milk diet would have measurable impacts on microbiome diversity as a potential mechanism [in] disease modulation as part of the mechanism by which exclusive human milk diets benefit preterm infants.”

Shortfalls in a mother’s own milk supply often necessitate the use of bovine formula or pasteurized human milk from donor milk banks or commercial suppliers.

The effect of an exclusive human milk diet versus one containing bovine products on vulnerable preterm infants is unclear, but some studies have shown lower rates of key neonatal morbidities, possibly mediated by the gut microbiome. In two randomized controlled trials, for example, one showed a lower rate of NEC with donated human milk while the other showed no difference.

Neither, however, was powered to detect a clinically important difference in surgical NEC.
 

Milk and the microbiome

The current study’s primary endpoint was the effect of an exclusive human milk diet on gut bacterial richness and diversity, as well as the proportions of specific microbial taxa in preterm infants from enrollment to 34 weeks’ postmenstrual age.

Conducted at four neonatal intensive care units in the United Kingdom from 2017 to 2020, the study recruited 126 infants born at less than 30 weeks’ gestation and fed exclusively with their own mother’s milk before 72 hours of age. With a median gestational age of 27 weeks and a median birth weight of just over 900 grams, the babies were randomized 1:1 either to their own mother’s milk plus a pasteurized ready-to-feed human milk product or to their mother’s milk plus a standard preterm formula (controls). Stool samples were collected to analyze intestinal microbiota.

In terms of clinical outcomes, four infants died in the standard-care control group and eight in the intervention group at a median postnatal age of 25 days and 15 days, respectively, but none died primarily of NEC. Formula and ready-to-feed human milk both represented less than 1% of all fluid intake, respectively.

Although there were no effects on overall measures of gut bacterial diversity, there were some insignificant effects on specific bacterial taxa previously associated with human milk feeding. “These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms,” the authors wrote.

Human milk could benefit, however, via components such as specific oligosaccharides, which act largely by modulating the growth of friendly Bifidobacteria and other species, Dr. Embleton said. “However, it’s possible these oligosaccharides might also directly interact via the gut epithelium as a signaling molecule. And, of course, there are many other components that might also act directly on the gut without changing the microbiome.”

*Commenting on the study but not involved in it, Brenda L. Poindexter, MD, MS, chief of the division of neonatology at Children’s Healthcare of Atlanta and Emory University, called it “incredibly important,” especially in the context of the claims of superiority made by the manufacturers of human-milk-based fortifiers. “These findings convincingly debunk the notion that the use of bovine-derived fortifiers increases risk of morbidities such as NEC through the mechanism of alterations in the microbiome, Dr. Poindexter said.

 “They refute that claim as there was no difference in NEC between the groups and, interestingly, no impact on the microbiome. One of the hypothesized mechanisms for those who purport that bovine fortifiers are ‘bad’ is that they alter the microbiome, which increases risk of NEC,” she said. “The only limitation is that the study was not powered to detect a difference in NEC, but it is incredibly important nonetheless.”

The current findings differ somewhat from those of a similar trial from 2022 showing lower microbial diversity and higher relative abundances of Enterobacteriaceae and lower abundances of Clostridium sensu stricto in preterm infants receiving an exclusive human milk diet. “These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window,” the authors wrote.

Dr. Embleton conceded that his group’s study set the bar deliberately high to avoid finding too many differences purely due to chance, and it therefore might have missed bacterial changes present in low proportions. “Also, the technique we used, 16s rRNA, doesn’t explore the microbiome at the strain level, so there may have been changes we didn’t detect.”

He added that the study populations also had a relatively high usage of mother’s own milk and findings may differ in other populations and settings where the use of mother’s own milk is much lower. Furthermore, the differences reported by individual hospitals in the babies’ gut microbiomes were more significant than most feeding interventions.

So can mothers needing to use nonhuman supplements be reassured by the results? “It is difficult to know how parents may interpret our findings. We need more studies powered to detect differences in functional outcomes before we can draw conclusions and share those findings in a way parents can understand,” Dr. Embleton said. “At present, there is perhaps a too simplistic message that cow milk formula is ‘harmful.’ ”

Most babies exposed to cow’s milk fortifier or formula do not develop NEC, and many with NEC have only ever received their own mother’s milk or donor milk, he added. “It could be that with advances in pasteurization or other similar techniques the quality and therefore the functional benefits of human milk can be better preserved.”

More research is needed on the mechanisms of preterm feeding interventions, including donor human milk, fortifiers, and probiotics, Dr. Embleton said. “The gut microbiome in preterm infants is complex and very different from that in term infants.”

The study was sponsored by Newcastle Hospitals NHS Foundation Trust and funded by Prolacta Biosciences, which provided human milk formula and fortifier. Dr. Embleton reported financial ties to Danone Early Life Nutrition, Nestlé Nutrition Institute Lecture, Astarte Lecture, and NeoKare outside of the submitted work. Several coauthors reported similar ties to multiple private companies and various research funding bodies. Dr. Poindexter has no conflicts of interest.

*This story was updated on March 3, 2023.

No significant differences emerged in gut microbial diversity in preterm infants who exclusively received human milk products, compared with those receiving bovine milk formula or fortifiers, a randomized controlled trial found. Nor were any differences noted in the secondary endpoint of clinical outcomes in the U.K. study, published online in JAMA Network Open.

Newcastle University

The finding was unanticipated, according to lead author Nicholas D. Embleton, MBBS, MD, a professor of neonatal medicine at Newcastle University in England. “Over the last 10 years we’ve focused particularly on the role of the microbiome to better understand causal mechanisms of necrotizing enterocolitis, or NEC,” he said in an interview. “We anticipated that an exclusive human milk diet would have measurable impacts on microbiome diversity as a potential mechanism [in] disease modulation as part of the mechanism by which exclusive human milk diets benefit preterm infants.”

Shortfalls in a mother’s own milk supply often necessitate the use of bovine formula or pasteurized human milk from donor milk banks or commercial suppliers.

The effect of an exclusive human milk diet versus one containing bovine products on vulnerable preterm infants is unclear, but some studies have shown lower rates of key neonatal morbidities, possibly mediated by the gut microbiome. In two randomized controlled trials, for example, one showed a lower rate of NEC with donated human milk while the other showed no difference.

Neither, however, was powered to detect a clinically important difference in surgical NEC.
 

Milk and the microbiome

The current study’s primary endpoint was the effect of an exclusive human milk diet on gut bacterial richness and diversity, as well as the proportions of specific microbial taxa in preterm infants from enrollment to 34 weeks’ postmenstrual age.

Conducted at four neonatal intensive care units in the United Kingdom from 2017 to 2020, the study recruited 126 infants born at less than 30 weeks’ gestation and fed exclusively with their own mother’s milk before 72 hours of age. With a median gestational age of 27 weeks and a median birth weight of just over 900 grams, the babies were randomized 1:1 either to their own mother’s milk plus a pasteurized ready-to-feed human milk product or to their mother’s milk plus a standard preterm formula (controls). Stool samples were collected to analyze intestinal microbiota.

In terms of clinical outcomes, four infants died in the standard-care control group and eight in the intervention group at a median postnatal age of 25 days and 15 days, respectively, but none died primarily of NEC. Formula and ready-to-feed human milk both represented less than 1% of all fluid intake, respectively.

Although there were no effects on overall measures of gut bacterial diversity, there were some insignificant effects on specific bacterial taxa previously associated with human milk feeding. “These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms,” the authors wrote.

Human milk could benefit, however, via components such as specific oligosaccharides, which act largely by modulating the growth of friendly Bifidobacteria and other species, Dr. Embleton said. “However, it’s possible these oligosaccharides might also directly interact via the gut epithelium as a signaling molecule. And, of course, there are many other components that might also act directly on the gut without changing the microbiome.”

*Commenting on the study but not involved in it, Brenda L. Poindexter, MD, MS, chief of the division of neonatology at Children’s Healthcare of Atlanta and Emory University, called it “incredibly important,” especially in the context of the claims of superiority made by the manufacturers of human-milk-based fortifiers. “These findings convincingly debunk the notion that the use of bovine-derived fortifiers increases risk of morbidities such as NEC through the mechanism of alterations in the microbiome, Dr. Poindexter said.

 “They refute that claim as there was no difference in NEC between the groups and, interestingly, no impact on the microbiome. One of the hypothesized mechanisms for those who purport that bovine fortifiers are ‘bad’ is that they alter the microbiome, which increases risk of NEC,” she said. “The only limitation is that the study was not powered to detect a difference in NEC, but it is incredibly important nonetheless.”

The current findings differ somewhat from those of a similar trial from 2022 showing lower microbial diversity and higher relative abundances of Enterobacteriaceae and lower abundances of Clostridium sensu stricto in preterm infants receiving an exclusive human milk diet. “These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window,” the authors wrote.

Dr. Embleton conceded that his group’s study set the bar deliberately high to avoid finding too many differences purely due to chance, and it therefore might have missed bacterial changes present in low proportions. “Also, the technique we used, 16s rRNA, doesn’t explore the microbiome at the strain level, so there may have been changes we didn’t detect.”

He added that the study populations also had a relatively high usage of mother’s own milk and findings may differ in other populations and settings where the use of mother’s own milk is much lower. Furthermore, the differences reported by individual hospitals in the babies’ gut microbiomes were more significant than most feeding interventions.

So can mothers needing to use nonhuman supplements be reassured by the results? “It is difficult to know how parents may interpret our findings. We need more studies powered to detect differences in functional outcomes before we can draw conclusions and share those findings in a way parents can understand,” Dr. Embleton said. “At present, there is perhaps a too simplistic message that cow milk formula is ‘harmful.’ ”

Most babies exposed to cow’s milk fortifier or formula do not develop NEC, and many with NEC have only ever received their own mother’s milk or donor milk, he added. “It could be that with advances in pasteurization or other similar techniques the quality and therefore the functional benefits of human milk can be better preserved.”

More research is needed on the mechanisms of preterm feeding interventions, including donor human milk, fortifiers, and probiotics, Dr. Embleton said. “The gut microbiome in preterm infants is complex and very different from that in term infants.”

The study was sponsored by Newcastle Hospitals NHS Foundation Trust and funded by Prolacta Biosciences, which provided human milk formula and fortifier. Dr. Embleton reported financial ties to Danone Early Life Nutrition, Nestlé Nutrition Institute Lecture, Astarte Lecture, and NeoKare outside of the submitted work. Several coauthors reported similar ties to multiple private companies and various research funding bodies. Dr. Poindexter has no conflicts of interest.

*This story was updated on March 3, 2023.

No significant differences emerged in gut microbial diversity in preterm infants who exclusively received human milk products, compared with those receiving bovine milk formula or fortifiers, a randomized controlled trial found. Nor were any differences noted in the secondary endpoint of clinical outcomes in the U.K. study, published online in JAMA Network Open.

Newcastle University

The finding was unanticipated, according to lead author Nicholas D. Embleton, MBBS, MD, a professor of neonatal medicine at Newcastle University in England. “Over the last 10 years we’ve focused particularly on the role of the microbiome to better understand causal mechanisms of necrotizing enterocolitis, or NEC,” he said in an interview. “We anticipated that an exclusive human milk diet would have measurable impacts on microbiome diversity as a potential mechanism [in] disease modulation as part of the mechanism by which exclusive human milk diets benefit preterm infants.”

Shortfalls in a mother’s own milk supply often necessitate the use of bovine formula or pasteurized human milk from donor milk banks or commercial suppliers.

The effect of an exclusive human milk diet versus one containing bovine products on vulnerable preterm infants is unclear, but some studies have shown lower rates of key neonatal morbidities, possibly mediated by the gut microbiome. In two randomized controlled trials, for example, one showed a lower rate of NEC with donated human milk while the other showed no difference.

Neither, however, was powered to detect a clinically important difference in surgical NEC.
 

Milk and the microbiome

The current study’s primary endpoint was the effect of an exclusive human milk diet on gut bacterial richness and diversity, as well as the proportions of specific microbial taxa in preterm infants from enrollment to 34 weeks’ postmenstrual age.

Conducted at four neonatal intensive care units in the United Kingdom from 2017 to 2020, the study recruited 126 infants born at less than 30 weeks’ gestation and fed exclusively with their own mother’s milk before 72 hours of age. With a median gestational age of 27 weeks and a median birth weight of just over 900 grams, the babies were randomized 1:1 either to their own mother’s milk plus a pasteurized ready-to-feed human milk product or to their mother’s milk plus a standard preterm formula (controls). Stool samples were collected to analyze intestinal microbiota.

In terms of clinical outcomes, four infants died in the standard-care control group and eight in the intervention group at a median postnatal age of 25 days and 15 days, respectively, but none died primarily of NEC. Formula and ready-to-feed human milk both represented less than 1% of all fluid intake, respectively.

Although there were no effects on overall measures of gut bacterial diversity, there were some insignificant effects on specific bacterial taxa previously associated with human milk feeding. “These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms,” the authors wrote.

Human milk could benefit, however, via components such as specific oligosaccharides, which act largely by modulating the growth of friendly Bifidobacteria and other species, Dr. Embleton said. “However, it’s possible these oligosaccharides might also directly interact via the gut epithelium as a signaling molecule. And, of course, there are many other components that might also act directly on the gut without changing the microbiome.”

*Commenting on the study but not involved in it, Brenda L. Poindexter, MD, MS, chief of the division of neonatology at Children’s Healthcare of Atlanta and Emory University, called it “incredibly important,” especially in the context of the claims of superiority made by the manufacturers of human-milk-based fortifiers. “These findings convincingly debunk the notion that the use of bovine-derived fortifiers increases risk of morbidities such as NEC through the mechanism of alterations in the microbiome, Dr. Poindexter said.

 “They refute that claim as there was no difference in NEC between the groups and, interestingly, no impact on the microbiome. One of the hypothesized mechanisms for those who purport that bovine fortifiers are ‘bad’ is that they alter the microbiome, which increases risk of NEC,” she said. “The only limitation is that the study was not powered to detect a difference in NEC, but it is incredibly important nonetheless.”

The current findings differ somewhat from those of a similar trial from 2022 showing lower microbial diversity and higher relative abundances of Enterobacteriaceae and lower abundances of Clostridium sensu stricto in preterm infants receiving an exclusive human milk diet. “These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window,” the authors wrote.

Dr. Embleton conceded that his group’s study set the bar deliberately high to avoid finding too many differences purely due to chance, and it therefore might have missed bacterial changes present in low proportions. “Also, the technique we used, 16s rRNA, doesn’t explore the microbiome at the strain level, so there may have been changes we didn’t detect.”

He added that the study populations also had a relatively high usage of mother’s own milk and findings may differ in other populations and settings where the use of mother’s own milk is much lower. Furthermore, the differences reported by individual hospitals in the babies’ gut microbiomes were more significant than most feeding interventions.

So can mothers needing to use nonhuman supplements be reassured by the results? “It is difficult to know how parents may interpret our findings. We need more studies powered to detect differences in functional outcomes before we can draw conclusions and share those findings in a way parents can understand,” Dr. Embleton said. “At present, there is perhaps a too simplistic message that cow milk formula is ‘harmful.’ ”

Most babies exposed to cow’s milk fortifier or formula do not develop NEC, and many with NEC have only ever received their own mother’s milk or donor milk, he added. “It could be that with advances in pasteurization or other similar techniques the quality and therefore the functional benefits of human milk can be better preserved.”

More research is needed on the mechanisms of preterm feeding interventions, including donor human milk, fortifiers, and probiotics, Dr. Embleton said. “The gut microbiome in preterm infants is complex and very different from that in term infants.”

The study was sponsored by Newcastle Hospitals NHS Foundation Trust and funded by Prolacta Biosciences, which provided human milk formula and fortifier. Dr. Embleton reported financial ties to Danone Early Life Nutrition, Nestlé Nutrition Institute Lecture, Astarte Lecture, and NeoKare outside of the submitted work. Several coauthors reported similar ties to multiple private companies and various research funding bodies. Dr. Poindexter has no conflicts of interest.

*This story was updated on March 3, 2023.

GnRH antagonists with estrogen/progesterone are promising new uterine-sparing options for treating uterine fibroids. Two experts review data from two recent clinical trials to bring you up to speed on the benefits and risks of this treatment approach.

After reading this short article, you have an opportunity to earn 1.0 CME credits.

Click here to read more

GnRH antagonists with estrogen/progesterone are promising new uterine-sparing options for treating uterine fibroids. Two experts review data from two recent clinical trials to bring you up to speed on the benefits and risks of this treatment approach.

After reading this short article, you have an opportunity to earn 1.0 CME credits.

Click here to read more

GnRH antagonists with estrogen/progesterone are promising new uterine-sparing options for treating uterine fibroids. Two experts review data from two recent clinical trials to bring you up to speed on the benefits and risks of this treatment approach.

After reading this short article, you have an opportunity to earn 1.0 CME credits.

Click here to read more

Cognition represents the most important function of the human brain and the essence of the mind. Cognitive functions such as memory, learning, comprehension, processing speed, attention, planning, and problem-solving are the best indicators of the status of brain health.

Many psychiatric brain disorders are associated with cognitive impairments. Decades of extensive research have documented that the most severe cognitive deficits occur in schizophrenia. No wonder Emil Kraepelin coined the term “dementia praecox,” which means premature dementia (in youth)¹ for this neuropsychiatric brain disorder. This condition was later renamed schizophrenia by Eugen Bleuler,² who regarded it primarily as a thought disorder, with splitting of associations (not split personality, as misinterpreted by many in the public). Interestingly, a century ago both of those early masters of psychiatry de-emphasized psychotic symptoms (delusions and hallucinations), regarding them as “supplemental symptoms.”³ Yet for the next 100 years, clinicians overemphasized psychotic symptoms in schizophrenia and overlooked the more disabling cognitive impairment and negative symptoms, referred to as Bleuler’s 4 A’s—Associations disruption, Ambivalence, Affect pathology, and Avolition—symptoms that persist even after the psychotic symptoms are successfully treated.³

Most contemporary researchers regard cognitive impairment as the “core” feature of schizophrenia.⁴ The justification of this view is that cognitive deficits are detected in childhood and early adolescence (by age 13),⁵ long before the appearance of psychotic symptoms, and many studies have confirmed that cognitive deficits are the primary cause of functional disability and unemployment of patients with schizophrenia. Cognitive dysfunction is also found in milder forms in the parents and siblings of patients with schizophrenia,⁶ and is thus considered an “endophenotype” of the illness.

Because of its centrality, cognition has emerged as a major focus of schizophrenia research over the past 20 years. Multiple stakeholders (academic investigators, the National Institute of Mental Health, and the FDA) have collaborated to develop a standard measurement for cognition in schizophrenia. The project culminated in what was labeled MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia).⁷ The MATRICS settled on a battery of 7 major cognitive functions that are often impaired in individuals with schizophrenia (Table 1⁸). Most contemporary researchers have adopted MATRICS in their studies, which facilitates replication to confirm research findings.

Measuring cognition in patients with schizophrenia is extremely important, as critical as measuring fasting glucose in patients with diabetes or blood pressure in patients with hypertension. Measuring the extent of impairment or nonimpairment across various cognitive tests can help with vocational rehabilitation, to place a patient in a job consistent with their level of cognitive functioning. In addition, once medications are developed and approved for cognitive impairments in schizophrenia, measuring cognition will be necessary to gauge the degree of improvement.

Currently, few psychiatric practitioners measure cognition in their patients. This is perplexing because cognitive measurement is important for confirming the diagnosis of schizophrenia in first-episode psychosis, or distinguishing it from other psychotic disorders (such as drug-induced psychosis, brief reactive psychosis, or delusional disorders) that do not have severe cognitive deficits.

The scores of various cognitive functions in individuals with schizophrenia range from .75 to 2.0 SD below the performance of the general population (matched for age and gender).⁹ This translates to dismally low percentiles of 2% and 24%. It is essential that all clinicians measure cognition in every patient with psychotic symptoms. It can be argued that cognition should even be measured in other psychiatric patients because cognitive deficits have been well documented in bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and other disorders, albeit not as severe as in schizophrenia, and these deficits usually correlate with the patient’s vocational and social functioning.

Continue to: So how is cognition measured...

So how is cognition measured, and can clinicians incorporate cognitive batteries in their practices? The most logical answer is to refer the patient to a board-certified neuropsychologist. These specialists are well-trained in assessing cognitive functions, and their evaluations generally are covered by health insurance. They use various validated cognitive batteries. Table 2^10-18 lists the currently recognized cognitive assessments and how much time they require. Psychiatrists can have nurses or medical assistants administer a brief cognitive test.

C-SARS: A self-rated cognition scale

Patient self-rating can provide psychiatric clinicians with valuable information, and is a time-saver. The widely used Patient Health Questionaire-9 (PHQ-9)¹⁹ is an excellent example of a self-rating scale for depression that enables patients to recognize and rate their depressive symptoms. It immediately informs the clinician how depressed their patient is and whether the severity of the depression has improved from the previous visit, which can indicate whether the prescribed medication is working. Based on the PHQ-9, which I regularly use—and recognizing that there is no cognition counterpart and that almost all clinicians could use a practical method of measuring their patients’ cognitive function—I developed an instrument called the Cognition Self-Assessment Rating Scale (C-SARS) (Table 3). The C-SARS can be completed online at https://curesz.org/csars/ and patients will be emailed the results within a minute. The C-SARS can be completed by the patient (with the help of their family or caregiver, if necessary, who observe the patient’s daily functioning, which corresponds to their cognition). The main purpose of the C-SARS is to inform the clinician about serious cognitive dysfunction in their patients, which should instigate a referral for formal neurocognitive assessment by a neuropsychology expert.

The items on the C-SARS reflect how well the patient is performing routine daily functions, each of which correlates with one of the cognitive domains of the MATRICS battery. Table 3 shows the 12 items in the C-SARS, their scoring, and their clinical implications (ie, when the results require referral for formal neurocognitive testing). In the future, when the FDA approves medications for addressing cognitive impairment (and several molecules are currently undergoing clinical trials), clinicians will be able to gauge a patient’s response to such treatments using the C-SARS and formal testing as needed. It may take several weeks to detect a significant reversal of cognitive deficits, but doing so would address a major unmet need in schizophrenia and may speed up vocational rehabilitation. The C-SARS also contains 2 items related to social cognition (items 11 and 12), which is also impaired in schizophrenia.²⁰ Future medications that improve social cognition in addition to neurocognition may also lead to improved social functioning among patients with schizophrenia.

In conclusion, the C-SARS, which needs to be validated in controlled studies, is the first cognition self-rating scale for schizophrenia and may be useful for other major psychiatric disorders. It will be a substantial time-saver for clinicians and will facilitate the routine incorporation of the cognitive assessment of patients with psychotic symptoms to help with the differential diagnosis of schizophrenia vs other psychotic disorders. Measuring cognitive functions is a vital step towards the valid diagnosis and treatment of this major clinical challenge in schizophrenia and improving patient outcomes in this serious psychiatric brain syndrome, in which up to 98% of patients have cognitive impairment across several domains.²¹

Cognition represents the most important function of the human brain and the essence of the mind. Cognitive functions such as memory, learning, comprehension, processing speed, attention, planning, and problem-solving are the best indicators of the status of brain health.

Many psychiatric brain disorders are associated with cognitive impairments. Decades of extensive research have documented that the most severe cognitive deficits occur in schizophrenia. No wonder Emil Kraepelin coined the term “dementia praecox,” which means premature dementia (in youth)¹ for this neuropsychiatric brain disorder. This condition was later renamed schizophrenia by Eugen Bleuler,² who regarded it primarily as a thought disorder, with splitting of associations (not split personality, as misinterpreted by many in the public). Interestingly, a century ago both of those early masters of psychiatry de-emphasized psychotic symptoms (delusions and hallucinations), regarding them as “supplemental symptoms.”³ Yet for the next 100 years, clinicians overemphasized psychotic symptoms in schizophrenia and overlooked the more disabling cognitive impairment and negative symptoms, referred to as Bleuler’s 4 A’s—Associations disruption, Ambivalence, Affect pathology, and Avolition—symptoms that persist even after the psychotic symptoms are successfully treated.³

Most contemporary researchers regard cognitive impairment as the “core” feature of schizophrenia.⁴ The justification of this view is that cognitive deficits are detected in childhood and early adolescence (by age 13),⁵ long before the appearance of psychotic symptoms, and many studies have confirmed that cognitive deficits are the primary cause of functional disability and unemployment of patients with schizophrenia. Cognitive dysfunction is also found in milder forms in the parents and siblings of patients with schizophrenia,⁶ and is thus considered an “endophenotype” of the illness.

Because of its centrality, cognition has emerged as a major focus of schizophrenia research over the past 20 years. Multiple stakeholders (academic investigators, the National Institute of Mental Health, and the FDA) have collaborated to develop a standard measurement for cognition in schizophrenia. The project culminated in what was labeled MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia).⁷ The MATRICS settled on a battery of 7 major cognitive functions that are often impaired in individuals with schizophrenia (Table 1⁸). Most contemporary researchers have adopted MATRICS in their studies, which facilitates replication to confirm research findings.

Measuring cognition in patients with schizophrenia is extremely important, as critical as measuring fasting glucose in patients with diabetes or blood pressure in patients with hypertension. Measuring the extent of impairment or nonimpairment across various cognitive tests can help with vocational rehabilitation, to place a patient in a job consistent with their level of cognitive functioning. In addition, once medications are developed and approved for cognitive impairments in schizophrenia, measuring cognition will be necessary to gauge the degree of improvement.

Currently, few psychiatric practitioners measure cognition in their patients. This is perplexing because cognitive measurement is important for confirming the diagnosis of schizophrenia in first-episode psychosis, or distinguishing it from other psychotic disorders (such as drug-induced psychosis, brief reactive psychosis, or delusional disorders) that do not have severe cognitive deficits.

The scores of various cognitive functions in individuals with schizophrenia range from .75 to 2.0 SD below the performance of the general population (matched for age and gender).⁹ This translates to dismally low percentiles of 2% and 24%. It is essential that all clinicians measure cognition in every patient with psychotic symptoms. It can be argued that cognition should even be measured in other psychiatric patients because cognitive deficits have been well documented in bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and other disorders, albeit not as severe as in schizophrenia, and these deficits usually correlate with the patient’s vocational and social functioning.

Continue to: So how is cognition measured...

So how is cognition measured, and can clinicians incorporate cognitive batteries in their practices? The most logical answer is to refer the patient to a board-certified neuropsychologist. These specialists are well-trained in assessing cognitive functions, and their evaluations generally are covered by health insurance. They use various validated cognitive batteries. Table 2^10-18 lists the currently recognized cognitive assessments and how much time they require. Psychiatrists can have nurses or medical assistants administer a brief cognitive test.

C-SARS: A self-rated cognition scale

Patient self-rating can provide psychiatric clinicians with valuable information, and is a time-saver. The widely used Patient Health Questionaire-9 (PHQ-9)¹⁹ is an excellent example of a self-rating scale for depression that enables patients to recognize and rate their depressive symptoms. It immediately informs the clinician how depressed their patient is and whether the severity of the depression has improved from the previous visit, which can indicate whether the prescribed medication is working. Based on the PHQ-9, which I regularly use—and recognizing that there is no cognition counterpart and that almost all clinicians could use a practical method of measuring their patients’ cognitive function—I developed an instrument called the Cognition Self-Assessment Rating Scale (C-SARS) (Table 3). The C-SARS can be completed online at https://curesz.org/csars/ and patients will be emailed the results within a minute. The C-SARS can be completed by the patient (with the help of their family or caregiver, if necessary, who observe the patient’s daily functioning, which corresponds to their cognition). The main purpose of the C-SARS is to inform the clinician about serious cognitive dysfunction in their patients, which should instigate a referral for formal neurocognitive assessment by a neuropsychology expert.

The items on the C-SARS reflect how well the patient is performing routine daily functions, each of which correlates with one of the cognitive domains of the MATRICS battery. Table 3 shows the 12 items in the C-SARS, their scoring, and their clinical implications (ie, when the results require referral for formal neurocognitive testing). In the future, when the FDA approves medications for addressing cognitive impairment (and several molecules are currently undergoing clinical trials), clinicians will be able to gauge a patient’s response to such treatments using the C-SARS and formal testing as needed. It may take several weeks to detect a significant reversal of cognitive deficits, but doing so would address a major unmet need in schizophrenia and may speed up vocational rehabilitation. The C-SARS also contains 2 items related to social cognition (items 11 and 12), which is also impaired in schizophrenia.²⁰ Future medications that improve social cognition in addition to neurocognition may also lead to improved social functioning among patients with schizophrenia.

In conclusion, the C-SARS, which needs to be validated in controlled studies, is the first cognition self-rating scale for schizophrenia and may be useful for other major psychiatric disorders. It will be a substantial time-saver for clinicians and will facilitate the routine incorporation of the cognitive assessment of patients with psychotic symptoms to help with the differential diagnosis of schizophrenia vs other psychotic disorders. Measuring cognitive functions is a vital step towards the valid diagnosis and treatment of this major clinical challenge in schizophrenia and improving patient outcomes in this serious psychiatric brain syndrome, in which up to 98% of patients have cognitive impairment across several domains.²¹

Cognition represents the most important function of the human brain and the essence of the mind. Cognitive functions such as memory, learning, comprehension, processing speed, attention, planning, and problem-solving are the best indicators of the status of brain health.

Many psychiatric brain disorders are associated with cognitive impairments. Decades of extensive research have documented that the most severe cognitive deficits occur in schizophrenia. No wonder Emil Kraepelin coined the term “dementia praecox,” which means premature dementia (in youth)¹ for this neuropsychiatric brain disorder. This condition was later renamed schizophrenia by Eugen Bleuler,² who regarded it primarily as a thought disorder, with splitting of associations (not split personality, as misinterpreted by many in the public). Interestingly, a century ago both of those early masters of psychiatry de-emphasized psychotic symptoms (delusions and hallucinations), regarding them as “supplemental symptoms.”³ Yet for the next 100 years, clinicians overemphasized psychotic symptoms in schizophrenia and overlooked the more disabling cognitive impairment and negative symptoms, referred to as Bleuler’s 4 A’s—Associations disruption, Ambivalence, Affect pathology, and Avolition—symptoms that persist even after the psychotic symptoms are successfully treated.³

Most contemporary researchers regard cognitive impairment as the “core” feature of schizophrenia.⁴ The justification of this view is that cognitive deficits are detected in childhood and early adolescence (by age 13),⁵ long before the appearance of psychotic symptoms, and many studies have confirmed that cognitive deficits are the primary cause of functional disability and unemployment of patients with schizophrenia. Cognitive dysfunction is also found in milder forms in the parents and siblings of patients with schizophrenia,⁶ and is thus considered an “endophenotype” of the illness.

Because of its centrality, cognition has emerged as a major focus of schizophrenia research over the past 20 years. Multiple stakeholders (academic investigators, the National Institute of Mental Health, and the FDA) have collaborated to develop a standard measurement for cognition in schizophrenia. The project culminated in what was labeled MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia).⁷ The MATRICS settled on a battery of 7 major cognitive functions that are often impaired in individuals with schizophrenia (Table 1⁸). Most contemporary researchers have adopted MATRICS in their studies, which facilitates replication to confirm research findings.

Measuring cognition in patients with schizophrenia is extremely important, as critical as measuring fasting glucose in patients with diabetes or blood pressure in patients with hypertension. Measuring the extent of impairment or nonimpairment across various cognitive tests can help with vocational rehabilitation, to place a patient in a job consistent with their level of cognitive functioning. In addition, once medications are developed and approved for cognitive impairments in schizophrenia, measuring cognition will be necessary to gauge the degree of improvement.

Currently, few psychiatric practitioners measure cognition in their patients. This is perplexing because cognitive measurement is important for confirming the diagnosis of schizophrenia in first-episode psychosis, or distinguishing it from other psychotic disorders (such as drug-induced psychosis, brief reactive psychosis, or delusional disorders) that do not have severe cognitive deficits.

The scores of various cognitive functions in individuals with schizophrenia range from .75 to 2.0 SD below the performance of the general population (matched for age and gender).⁹ This translates to dismally low percentiles of 2% and 24%. It is essential that all clinicians measure cognition in every patient with psychotic symptoms. It can be argued that cognition should even be measured in other psychiatric patients because cognitive deficits have been well documented in bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and other disorders, albeit not as severe as in schizophrenia, and these deficits usually correlate with the patient’s vocational and social functioning.

Continue to: So how is cognition measured...

So how is cognition measured, and can clinicians incorporate cognitive batteries in their practices? The most logical answer is to refer the patient to a board-certified neuropsychologist. These specialists are well-trained in assessing cognitive functions, and their evaluations generally are covered by health insurance. They use various validated cognitive batteries. Table 2^10-18 lists the currently recognized cognitive assessments and how much time they require. Psychiatrists can have nurses or medical assistants administer a brief cognitive test.

C-SARS: A self-rated cognition scale

Patient self-rating can provide psychiatric clinicians with valuable information, and is a time-saver. The widely used Patient Health Questionaire-9 (PHQ-9)¹⁹ is an excellent example of a self-rating scale for depression that enables patients to recognize and rate their depressive symptoms. It immediately informs the clinician how depressed their patient is and whether the severity of the depression has improved from the previous visit, which can indicate whether the prescribed medication is working. Based on the PHQ-9, which I regularly use—and recognizing that there is no cognition counterpart and that almost all clinicians could use a practical method of measuring their patients’ cognitive function—I developed an instrument called the Cognition Self-Assessment Rating Scale (C-SARS) (Table 3). The C-SARS can be completed online at https://curesz.org/csars/ and patients will be emailed the results within a minute. The C-SARS can be completed by the patient (with the help of their family or caregiver, if necessary, who observe the patient’s daily functioning, which corresponds to their cognition). The main purpose of the C-SARS is to inform the clinician about serious cognitive dysfunction in their patients, which should instigate a referral for formal neurocognitive assessment by a neuropsychology expert.

The items on the C-SARS reflect how well the patient is performing routine daily functions, each of which correlates with one of the cognitive domains of the MATRICS battery. Table 3 shows the 12 items in the C-SARS, their scoring, and their clinical implications (ie, when the results require referral for formal neurocognitive testing). In the future, when the FDA approves medications for addressing cognitive impairment (and several molecules are currently undergoing clinical trials), clinicians will be able to gauge a patient’s response to such treatments using the C-SARS and formal testing as needed. It may take several weeks to detect a significant reversal of cognitive deficits, but doing so would address a major unmet need in schizophrenia and may speed up vocational rehabilitation. The C-SARS also contains 2 items related to social cognition (items 11 and 12), which is also impaired in schizophrenia.²⁰ Future medications that improve social cognition in addition to neurocognition may also lead to improved social functioning among patients with schizophrenia.

In conclusion, the C-SARS, which needs to be validated in controlled studies, is the first cognition self-rating scale for schizophrenia and may be useful for other major psychiatric disorders. It will be a substantial time-saver for clinicians and will facilitate the routine incorporation of the cognitive assessment of patients with psychotic symptoms to help with the differential diagnosis of schizophrenia vs other psychotic disorders. Measuring cognitive functions is a vital step towards the valid diagnosis and treatment of this major clinical challenge in schizophrenia and improving patient outcomes in this serious psychiatric brain syndrome, in which up to 98% of patients have cognitive impairment across several domains.²¹

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

Ayahuasca is a psychoactive beverage that has long been used by indigenous people in South America in religious ceremonies and tribal rituals. In recent years, the beverage has emerged as a strong candidate for implementation into psychiatric care, particularly for patients with treatment-resistant depression.

Studies have shown that taking ayahuasca is associated with an improvement of depressive symptoms. In a study published in Frontiers in Psychiatry, a team of researchers from Brazil’s Federal University of Rio Grande do Norte (UFRN) describe an experimental ayahuasca session. They found that specific emotional and physiologic parameters were critical moderators of improvement in major depression biomarkers, mainly serum brain-derived neurotrophic factor (BDNF) and serum cortisol (SC), 2 days after ayahuasca intake.

Nicole Leite Galvão-Coelho, PhD, professor of physiology and behavior at UFRN, is one of the authors of that study. She is also a researcher at the NICM Health Research Institute at Western Sydney University. Dr. Galvão-Coelho spoke with this news organization about her team’s work.

A total of 72 people volunteered to participate in the study. There were 28 patients, all of whom were experiencing a moderate to severe depressive episode at screening. In addition, they had been diagnosed with treatment-resistant depression and had not achieved remission after at least two treatments with antidepressant medications of different classes. These patients had been experiencing depression for about 10.71 ± 9.72 years. The other 44 volunteers were healthy control participants. All the participants – both in the patient group and the control group – were naive to any classic serotonergic psychedelic such as ayahuasca.

In each group, half received ayahuasca, and the other half received a placebo. The dosing session was performed at UFRN’s Onofre Lopes University Hospital and lasted about 8 hours.

All volunteers underwent a full clinical mental health evaluation and medical history. Blood and saliva samples were collected at baseline, approximately 4 hours before the dosing session, and 2 days after the dosing session. During the dosing session, saliva samples were collected at 1 hour 40 minutes, 2 hours 40 minutes, and 4 hours after ayahuasca intake.

The study showed that some acute measures assessed during ayahuasca dosing moderated the improvements in major depressive disorder (MDD) biomarkers 2 days after the session in patients with treatment-resistant depression. Larger acute decreases of depressive symptoms moderated higher levels of SC in those patients, while lower acute changes in SC levels were related to higher BDNF levels in patients with a larger clinical response.

The UFRN research team has been investigating the potential antidepressant effects of ayahuasca for approximately 12 years. According to Dr. Galvão-Coelho, the work reported in the most recent article – one in a series of articles that they wrote – provides a step forward as a pioneering psychedelic field study assessing the biological changes of MDD molecular biomarkers. “There have indeed been observational studies and open-label clinical studies. We were the first team, though, to conduct placebo-controlled clinical studies with ayahuasca in patients with treatment-resistant depression,” she explained. She noted that the work was carried out in partnership with Dráulio Barros de Araújo, PhD, a professor at UFRN’s Brain Institute, as well as with a multidisciplinary team of researchers in Brazil and Australia.

Dr. Galvão-Coelho said that in an earlier study, the UFRN researchers observed that a single dose of ayahuasca led to long-lasting behavioral and physiologic improvements in an animal (marmoset) model. In another study, there was improvement in depression severity for patients with treatment-resistant depression 7 days after taking ayahuasca.

As for biomarkers, Dr. Galvão-Coelho said that there is a long history of research on cortisol (the “stress hormone”) with respect to patients with depressive symptoms, given the link between chronic stress and depressive disorders. “In our patients with treatment-resistant depression, we found that before being dosed with ayahuasca, they presented hypocortisolemia,” she said. She noted that low levels of cortisol are as harmful to one’s health as high levels. According to her, the goal should be to sustain moderate levels. “In other studies, we’ve shown that patients with more recent, less chronic depression have high cortisol levels, but after a little while, the [adrenal] glands get overworked, which seems to lead to a situation where they’re not producing all those important hormones. That’s why chronic conditions of depression are marked by low levels of cortisol. But,” she pointed out, “after patients with treatment-resistant depression take ayahuasca, we no longer see hypocortisolemia.”

Another biomarker analyzed by the research team, the protein BDNF, has the capacity to induce neuroplasticity. Indeed, Dr. Galvão-Coelho mentioned a theory that antidepressant drugs work when they increase levels of this protein, which would stimulate new connections in the brain.

Because several earlier studies indicated that other psychedelic substances would promote an increase in BDNF, the UFRN researchers decided to explore the potential effects of ayahuasca on this biomarker. “We observed that there was actually an increase in serum BDNF, and the patients who showed the greatest increase [of this marker] had a more significant reduction in depressive symptoms,” Dr. Galvão-Coelho explained.

Considering all the previous findings, the team wondered whether acute parameters recorded during an ayahuasca dosing session could in some way modulate the responses of certain key MDD molecular biomarkers. They then conducted their study that was published last December.

Dr. Galvão-Coelho said that the results of that study show that acute emotional and physiologic effects of ayahuasca seem to be relevant to an improvement of key MDD molecular biomarkers (namely, SC and BDNF). She also noted that the results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients 2 days after ayahuasca intake. In the case of BDNF, the positive correlation between clinical response and day-2 BDNF levels only occurred for patients who experienced small increases of cortisol during the experimental session. These were individuals who did not have such an intense response to stress and who felt more at ease during the session.

The findings showed which factors that arise during the psychedelic state induced by ayahuasca modulate biological response associated with the antidepressant action of these substances in patients with major depression. “We realized, for example, that to bring about a sense of comfort and trust, to get a good acute response, the dosing session had to be extremely well thought out. That seemed to be relevant to the results on the other days,” Dr. Galvão-Coelho explained.

For her, there was another takeaway from the research: New antidepressant treatments should be complemented by a more comprehensive view of the case at hand. “We have to think about the patient’s overall improvement – including, therefore, the improvement of biomarkers – and not focus solely on the clinical symptoms.”

This article was translated from the Medscape Portuguese Edition.

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

Ayahuasca is a psychoactive beverage that has long been used by indigenous people in South America in religious ceremonies and tribal rituals. In recent years, the beverage has emerged as a strong candidate for implementation into psychiatric care, particularly for patients with treatment-resistant depression.

Studies have shown that taking ayahuasca is associated with an improvement of depressive symptoms. In a study published in Frontiers in Psychiatry, a team of researchers from Brazil’s Federal University of Rio Grande do Norte (UFRN) describe an experimental ayahuasca session. They found that specific emotional and physiologic parameters were critical moderators of improvement in major depression biomarkers, mainly serum brain-derived neurotrophic factor (BDNF) and serum cortisol (SC), 2 days after ayahuasca intake.

Nicole Leite Galvão-Coelho, PhD, professor of physiology and behavior at UFRN, is one of the authors of that study. She is also a researcher at the NICM Health Research Institute at Western Sydney University. Dr. Galvão-Coelho spoke with this news organization about her team’s work.

A total of 72 people volunteered to participate in the study. There were 28 patients, all of whom were experiencing a moderate to severe depressive episode at screening. In addition, they had been diagnosed with treatment-resistant depression and had not achieved remission after at least two treatments with antidepressant medications of different classes. These patients had been experiencing depression for about 10.71 ± 9.72 years. The other 44 volunteers were healthy control participants. All the participants – both in the patient group and the control group – were naive to any classic serotonergic psychedelic such as ayahuasca.

In each group, half received ayahuasca, and the other half received a placebo. The dosing session was performed at UFRN’s Onofre Lopes University Hospital and lasted about 8 hours.

All volunteers underwent a full clinical mental health evaluation and medical history. Blood and saliva samples were collected at baseline, approximately 4 hours before the dosing session, and 2 days after the dosing session. During the dosing session, saliva samples were collected at 1 hour 40 minutes, 2 hours 40 minutes, and 4 hours after ayahuasca intake.

The study showed that some acute measures assessed during ayahuasca dosing moderated the improvements in major depressive disorder (MDD) biomarkers 2 days after the session in patients with treatment-resistant depression. Larger acute decreases of depressive symptoms moderated higher levels of SC in those patients, while lower acute changes in SC levels were related to higher BDNF levels in patients with a larger clinical response.

The UFRN research team has been investigating the potential antidepressant effects of ayahuasca for approximately 12 years. According to Dr. Galvão-Coelho, the work reported in the most recent article – one in a series of articles that they wrote – provides a step forward as a pioneering psychedelic field study assessing the biological changes of MDD molecular biomarkers. “There have indeed been observational studies and open-label clinical studies. We were the first team, though, to conduct placebo-controlled clinical studies with ayahuasca in patients with treatment-resistant depression,” she explained. She noted that the work was carried out in partnership with Dráulio Barros de Araújo, PhD, a professor at UFRN’s Brain Institute, as well as with a multidisciplinary team of researchers in Brazil and Australia.

Dr. Galvão-Coelho said that in an earlier study, the UFRN researchers observed that a single dose of ayahuasca led to long-lasting behavioral and physiologic improvements in an animal (marmoset) model. In another study, there was improvement in depression severity for patients with treatment-resistant depression 7 days after taking ayahuasca.

As for biomarkers, Dr. Galvão-Coelho said that there is a long history of research on cortisol (the “stress hormone”) with respect to patients with depressive symptoms, given the link between chronic stress and depressive disorders. “In our patients with treatment-resistant depression, we found that before being dosed with ayahuasca, they presented hypocortisolemia,” she said. She noted that low levels of cortisol are as harmful to one’s health as high levels. According to her, the goal should be to sustain moderate levels. “In other studies, we’ve shown that patients with more recent, less chronic depression have high cortisol levels, but after a little while, the [adrenal] glands get overworked, which seems to lead to a situation where they’re not producing all those important hormones. That’s why chronic conditions of depression are marked by low levels of cortisol. But,” she pointed out, “after patients with treatment-resistant depression take ayahuasca, we no longer see hypocortisolemia.”

Another biomarker analyzed by the research team, the protein BDNF, has the capacity to induce neuroplasticity. Indeed, Dr. Galvão-Coelho mentioned a theory that antidepressant drugs work when they increase levels of this protein, which would stimulate new connections in the brain.

Because several earlier studies indicated that other psychedelic substances would promote an increase in BDNF, the UFRN researchers decided to explore the potential effects of ayahuasca on this biomarker. “We observed that there was actually an increase in serum BDNF, and the patients who showed the greatest increase [of this marker] had a more significant reduction in depressive symptoms,” Dr. Galvão-Coelho explained.

Considering all the previous findings, the team wondered whether acute parameters recorded during an ayahuasca dosing session could in some way modulate the responses of certain key MDD molecular biomarkers. They then conducted their study that was published last December.

Dr. Galvão-Coelho said that the results of that study show that acute emotional and physiologic effects of ayahuasca seem to be relevant to an improvement of key MDD molecular biomarkers (namely, SC and BDNF). She also noted that the results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients 2 days after ayahuasca intake. In the case of BDNF, the positive correlation between clinical response and day-2 BDNF levels only occurred for patients who experienced small increases of cortisol during the experimental session. These were individuals who did not have such an intense response to stress and who felt more at ease during the session.

The findings showed which factors that arise during the psychedelic state induced by ayahuasca modulate biological response associated with the antidepressant action of these substances in patients with major depression. “We realized, for example, that to bring about a sense of comfort and trust, to get a good acute response, the dosing session had to be extremely well thought out. That seemed to be relevant to the results on the other days,” Dr. Galvão-Coelho explained.

For her, there was another takeaway from the research: New antidepressant treatments should be complemented by a more comprehensive view of the case at hand. “We have to think about the patient’s overall improvement – including, therefore, the improvement of biomarkers – and not focus solely on the clinical symptoms.”

This article was translated from the Medscape Portuguese Edition.

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

Ayahuasca is a psychoactive beverage that has long been used by indigenous people in South America in religious ceremonies and tribal rituals. In recent years, the beverage has emerged as a strong candidate for implementation into psychiatric care, particularly for patients with treatment-resistant depression.

Studies have shown that taking ayahuasca is associated with an improvement of depressive symptoms. In a study published in Frontiers in Psychiatry, a team of researchers from Brazil’s Federal University of Rio Grande do Norte (UFRN) describe an experimental ayahuasca session. They found that specific emotional and physiologic parameters were critical moderators of improvement in major depression biomarkers, mainly serum brain-derived neurotrophic factor (BDNF) and serum cortisol (SC), 2 days after ayahuasca intake.

Nicole Leite Galvão-Coelho, PhD, professor of physiology and behavior at UFRN, is one of the authors of that study. She is also a researcher at the NICM Health Research Institute at Western Sydney University. Dr. Galvão-Coelho spoke with this news organization about her team’s work.

A total of 72 people volunteered to participate in the study. There were 28 patients, all of whom were experiencing a moderate to severe depressive episode at screening. In addition, they had been diagnosed with treatment-resistant depression and had not achieved remission after at least two treatments with antidepressant medications of different classes. These patients had been experiencing depression for about 10.71 ± 9.72 years. The other 44 volunteers were healthy control participants. All the participants – both in the patient group and the control group – were naive to any classic serotonergic psychedelic such as ayahuasca.

In each group, half received ayahuasca, and the other half received a placebo. The dosing session was performed at UFRN’s Onofre Lopes University Hospital and lasted about 8 hours.

All volunteers underwent a full clinical mental health evaluation and medical history. Blood and saliva samples were collected at baseline, approximately 4 hours before the dosing session, and 2 days after the dosing session. During the dosing session, saliva samples were collected at 1 hour 40 minutes, 2 hours 40 minutes, and 4 hours after ayahuasca intake.

The study showed that some acute measures assessed during ayahuasca dosing moderated the improvements in major depressive disorder (MDD) biomarkers 2 days after the session in patients with treatment-resistant depression. Larger acute decreases of depressive symptoms moderated higher levels of SC in those patients, while lower acute changes in SC levels were related to higher BDNF levels in patients with a larger clinical response.

The UFRN research team has been investigating the potential antidepressant effects of ayahuasca for approximately 12 years. According to Dr. Galvão-Coelho, the work reported in the most recent article – one in a series of articles that they wrote – provides a step forward as a pioneering psychedelic field study assessing the biological changes of MDD molecular biomarkers. “There have indeed been observational studies and open-label clinical studies. We were the first team, though, to conduct placebo-controlled clinical studies with ayahuasca in patients with treatment-resistant depression,” she explained. She noted that the work was carried out in partnership with Dráulio Barros de Araújo, PhD, a professor at UFRN’s Brain Institute, as well as with a multidisciplinary team of researchers in Brazil and Australia.

Dr. Galvão-Coelho said that in an earlier study, the UFRN researchers observed that a single dose of ayahuasca led to long-lasting behavioral and physiologic improvements in an animal (marmoset) model. In another study, there was improvement in depression severity for patients with treatment-resistant depression 7 days after taking ayahuasca.

As for biomarkers, Dr. Galvão-Coelho said that there is a long history of research on cortisol (the “stress hormone”) with respect to patients with depressive symptoms, given the link between chronic stress and depressive disorders. “In our patients with treatment-resistant depression, we found that before being dosed with ayahuasca, they presented hypocortisolemia,” she said. She noted that low levels of cortisol are as harmful to one’s health as high levels. According to her, the goal should be to sustain moderate levels. “In other studies, we’ve shown that patients with more recent, less chronic depression have high cortisol levels, but after a little while, the [adrenal] glands get overworked, which seems to lead to a situation where they’re not producing all those important hormones. That’s why chronic conditions of depression are marked by low levels of cortisol. But,” she pointed out, “after patients with treatment-resistant depression take ayahuasca, we no longer see hypocortisolemia.”

Another biomarker analyzed by the research team, the protein BDNF, has the capacity to induce neuroplasticity. Indeed, Dr. Galvão-Coelho mentioned a theory that antidepressant drugs work when they increase levels of this protein, which would stimulate new connections in the brain.

Because several earlier studies indicated that other psychedelic substances would promote an increase in BDNF, the UFRN researchers decided to explore the potential effects of ayahuasca on this biomarker. “We observed that there was actually an increase in serum BDNF, and the patients who showed the greatest increase [of this marker] had a more significant reduction in depressive symptoms,” Dr. Galvão-Coelho explained.

Considering all the previous findings, the team wondered whether acute parameters recorded during an ayahuasca dosing session could in some way modulate the responses of certain key MDD molecular biomarkers. They then conducted their study that was published last December.

Dr. Galvão-Coelho said that the results of that study show that acute emotional and physiologic effects of ayahuasca seem to be relevant to an improvement of key MDD molecular biomarkers (namely, SC and BDNF). She also noted that the results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients 2 days after ayahuasca intake. In the case of BDNF, the positive correlation between clinical response and day-2 BDNF levels only occurred for patients who experienced small increases of cortisol during the experimental session. These were individuals who did not have such an intense response to stress and who felt more at ease during the session.

The findings showed which factors that arise during the psychedelic state induced by ayahuasca modulate biological response associated with the antidepressant action of these substances in patients with major depression. “We realized, for example, that to bring about a sense of comfort and trust, to get a good acute response, the dosing session had to be extremely well thought out. That seemed to be relevant to the results on the other days,” Dr. Galvão-Coelho explained.

For her, there was another takeaway from the research: New antidepressant treatments should be complemented by a more comprehensive view of the case at hand. “We have to think about the patient’s overall improvement – including, therefore, the improvement of biomarkers – and not focus solely on the clinical symptoms.”

This article was translated from the Medscape Portuguese Edition.

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

Adding simvastatin to standard therapy offers no benefit over placebo for patients with treatment-resistant depression (TRD), new research shows.

The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.

“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.

“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.

The findings were published online in JAMA Network Open.
 

Disappointing results

The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.

In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).

At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).

Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.

“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.

The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.

It is also unlikely that a different statin would yield different results, he added.

“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”

The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.

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

Adding simvastatin to standard therapy offers no benefit over placebo for patients with treatment-resistant depression (TRD), new research shows.

The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.

“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.

“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.

The findings were published online in JAMA Network Open.
 

Disappointing results

The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.

In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).

At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).

Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.

“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.

The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.

It is also unlikely that a different statin would yield different results, he added.

“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”

The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.

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

Adding simvastatin to standard therapy offers no benefit over placebo for patients with treatment-resistant depression (TRD), new research shows.

The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.

“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.

“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.

The findings were published online in JAMA Network Open.
 

Disappointing results

The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.

In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).

At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).

Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.

“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.

The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.

It is also unlikely that a different statin would yield different results, he added.

“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”

The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.

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