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The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.