SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.