Parent concerns a factor when treating eczema in children with darker skin types

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NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

Dr. Candrice R. Heath

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

 

 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

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NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

Dr. Candrice R. Heath

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

 

 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

Dr. Candrice R. Heath

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

 

 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

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Redispensing unused cancer meds cuts waste, saves money

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TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

  • Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
  • Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
  • Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
  • The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

  • A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
  • Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
  • Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
  • When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

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TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

  • Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
  • Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
  • Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
  • The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

  • A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
  • Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
  • Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
  • When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

 

TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

  • Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
  • Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
  • Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
  • The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

  • A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
  • Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
  • Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
  • When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

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Are we ready for systematic newborn genome sequencing?

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Will the traditional newborn screening program developed 60 years ago by Dr. Robert Guthrie soon be superseded by genome screening at birth? Routine sampling and analysis of newborn DNA would allow us to screen for many hundreds of childhood genetic diseases. This is the claim made by David Geneviève, MD, PhD, chair of the French Association of Clinical Geneticists and lecturer at the University of Montpellier (France), at the 9th annual conference of the French Society of Predictive and Personalized Medicine.

To date, newborn screening has consisted of taking a drop of blood from a newborn’s heel. In the future, DNA samples could be taken from babies for whole genome sequencing to look for diseases that are likely to crop up later in life.
 

The challenge

“In France, nearly all of the 720,000 babies born each year undergo newborn screening (only 300 refuse),” said Dr. Geneviève. For 60 years, newborn screening has tested for phenylketonuria, congenital hypothyroidism, congenital adrenal hyperplasia, sickle cell disease, cystic fibrosis, and medium-chain acyl-coenzyme A dehydrogenase deficiency.

On Jan. 1, 2023, France’s national newborn screening program added seven new diseases, bringing the number of rare diseases screened for to 13. The new diseases are homocystinuria, maple syrup urine disease, tyrosinemia type 1, isovaleric acidemia, glutaric aciduria type I, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, and carnitine deficiency.

“There aren’t just 13 childhood diseases,” continued Dr. Geneviève. “There are several hundred rare diseases, and genome sequencing tools allow us to broaden our screening capabilities. It’s inevitable that the ability to sequence your child’s genome at birth will become a possibility. It’s highly likely that within 10-15 years, all newborns will have their genome determined at birth for screening purposes.”

Current international trials

Genome sequencing has already been studied for several years in multiple countries. New York’s Guardian study requires all newborns taking part to undergo genome sequencing. “Our English-speaking colleagues use the genome to screen for childhood diseases that would benefit from treatment (235 can be treated) but also as a preventive measure and a way of providing early therapeutic education,” said Dr. Geneviève.

In 2016, American researchers launched the BabySeq Project, which was conducted at several sites (Boston, New York, Birmingham, Detroit, and Philadelphia). One of its aims is to assess the medical, psychological, and financial impact of screening via genome sequencing at birth, compared with conventional screening.

In North Carolina, 25,000 newborns took part in the Early Check study, a neonatal genetic screening project focusing on childhood spinal muscular atrophy, fragile X syndrome, and Duchenne muscular dystrophy.

In the United Kingdom, Genomics England seeks to assess the feasibility, benefits, and risks of whole genome sequencing as part of the Newborn Genomes Programme, an analysis of 100,000 newborn genomes. Projects are also underway in Belgium, Italy, and France (PeriGEN MED in Dijon).
 

Dijon’s specialist team

The conditions for considering neonatal screening of a disease are determined by the health care authorities in each country and vary greatly from one state to the next.

To date, in France, the only genetic screening authorized is for childhood spinal muscular atrophy via identification of an anomaly on SMN1. It has not yet been implemented, but a pilot study of its use is underway.

“If we are able to identify the 40 newborns affected by spinal muscular atrophy from birth, we can offer these patients gene therapy and stop them from dying at 1 or 2 years of age,” said Dr. Geneviève.

In the future, France should draw up a list of diseases for which genetic screening is useful, he added.

Although France’s initiative for genomic medicine, France Génomique 2025, does not envisage a neonatal genome sequencing screening program, a team in Dijon is studying several dozen genomes to determine the medical and financial benefits of such a program, explained Dr. Geneviève.
 

 

 

Ethical issues

Of course, this technological achievement raises ethical issues. “What do we do with the genetic data obtained at birth that won’t become apparent until adulthood, if we find a BRCA1 or BRCA2 variant in a newborn’s genome?” asked Dr. Genevieve.

Will the information obtained be stored somewhere? “This is a real issue,” he said. “The English have a national system. In their newborn screening program, when an infant grows into adulthood, he or she can have access to the genetic data.”

There is also a big risk that women will be pressured to undergo genetic testing during pregnancy. “No genome-related antenatal tests are carried out unless there are concerning ultrasound findings and only to look for particularly severe incurable diseases,” said Dr. Geneviève.
 

Not like Gattaca*

Financial obstacles should be quickly pushed aside. The cost of genome sequencing has decreased in the past few years. The first sequencing in 2003 cost close to $3 billion. Nowadays, it can be done for less than 1,000 € (just over $1,000).

Although neonatal genetic screening would enable us to limit the development of serious diseases, the decision to use such testing routinely must be made by society as a whole, Dr. Geneviève concluded.

“We often oppose preventive and personalized treatment strategies. Now the two have joined forces,” said Pascal Pujol, MD, PhD, chair of SFMPP.

For Dr. Pujol, broadening the application of genome sequencing is a no-brainer. “It won’t be like in Gattaca,” he reassures us. “It wouldn’t be done to determine a person’s character but [rather] to prevent those rare diseases that affect 4 to 5% of the population.”

*A reference to Andrew Niccol’s 1997 science fiction movie Gattaca. The film is set in a futuristic world in which parents can choose the genotype of their children to conceive test-tube babies with the fewest defects and the most advantages possible for society.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

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Will the traditional newborn screening program developed 60 years ago by Dr. Robert Guthrie soon be superseded by genome screening at birth? Routine sampling and analysis of newborn DNA would allow us to screen for many hundreds of childhood genetic diseases. This is the claim made by David Geneviève, MD, PhD, chair of the French Association of Clinical Geneticists and lecturer at the University of Montpellier (France), at the 9th annual conference of the French Society of Predictive and Personalized Medicine.

To date, newborn screening has consisted of taking a drop of blood from a newborn’s heel. In the future, DNA samples could be taken from babies for whole genome sequencing to look for diseases that are likely to crop up later in life.
 

The challenge

“In France, nearly all of the 720,000 babies born each year undergo newborn screening (only 300 refuse),” said Dr. Geneviève. For 60 years, newborn screening has tested for phenylketonuria, congenital hypothyroidism, congenital adrenal hyperplasia, sickle cell disease, cystic fibrosis, and medium-chain acyl-coenzyme A dehydrogenase deficiency.

On Jan. 1, 2023, France’s national newborn screening program added seven new diseases, bringing the number of rare diseases screened for to 13. The new diseases are homocystinuria, maple syrup urine disease, tyrosinemia type 1, isovaleric acidemia, glutaric aciduria type I, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, and carnitine deficiency.

“There aren’t just 13 childhood diseases,” continued Dr. Geneviève. “There are several hundred rare diseases, and genome sequencing tools allow us to broaden our screening capabilities. It’s inevitable that the ability to sequence your child’s genome at birth will become a possibility. It’s highly likely that within 10-15 years, all newborns will have their genome determined at birth for screening purposes.”

Current international trials

Genome sequencing has already been studied for several years in multiple countries. New York’s Guardian study requires all newborns taking part to undergo genome sequencing. “Our English-speaking colleagues use the genome to screen for childhood diseases that would benefit from treatment (235 can be treated) but also as a preventive measure and a way of providing early therapeutic education,” said Dr. Geneviève.

In 2016, American researchers launched the BabySeq Project, which was conducted at several sites (Boston, New York, Birmingham, Detroit, and Philadelphia). One of its aims is to assess the medical, psychological, and financial impact of screening via genome sequencing at birth, compared with conventional screening.

In North Carolina, 25,000 newborns took part in the Early Check study, a neonatal genetic screening project focusing on childhood spinal muscular atrophy, fragile X syndrome, and Duchenne muscular dystrophy.

In the United Kingdom, Genomics England seeks to assess the feasibility, benefits, and risks of whole genome sequencing as part of the Newborn Genomes Programme, an analysis of 100,000 newborn genomes. Projects are also underway in Belgium, Italy, and France (PeriGEN MED in Dijon).
 

Dijon’s specialist team

The conditions for considering neonatal screening of a disease are determined by the health care authorities in each country and vary greatly from one state to the next.

To date, in France, the only genetic screening authorized is for childhood spinal muscular atrophy via identification of an anomaly on SMN1. It has not yet been implemented, but a pilot study of its use is underway.

“If we are able to identify the 40 newborns affected by spinal muscular atrophy from birth, we can offer these patients gene therapy and stop them from dying at 1 or 2 years of age,” said Dr. Geneviève.

In the future, France should draw up a list of diseases for which genetic screening is useful, he added.

Although France’s initiative for genomic medicine, France Génomique 2025, does not envisage a neonatal genome sequencing screening program, a team in Dijon is studying several dozen genomes to determine the medical and financial benefits of such a program, explained Dr. Geneviève.
 

 

 

Ethical issues

Of course, this technological achievement raises ethical issues. “What do we do with the genetic data obtained at birth that won’t become apparent until adulthood, if we find a BRCA1 or BRCA2 variant in a newborn’s genome?” asked Dr. Genevieve.

Will the information obtained be stored somewhere? “This is a real issue,” he said. “The English have a national system. In their newborn screening program, when an infant grows into adulthood, he or she can have access to the genetic data.”

There is also a big risk that women will be pressured to undergo genetic testing during pregnancy. “No genome-related antenatal tests are carried out unless there are concerning ultrasound findings and only to look for particularly severe incurable diseases,” said Dr. Geneviève.
 

Not like Gattaca*

Financial obstacles should be quickly pushed aside. The cost of genome sequencing has decreased in the past few years. The first sequencing in 2003 cost close to $3 billion. Nowadays, it can be done for less than 1,000 € (just over $1,000).

Although neonatal genetic screening would enable us to limit the development of serious diseases, the decision to use such testing routinely must be made by society as a whole, Dr. Geneviève concluded.

“We often oppose preventive and personalized treatment strategies. Now the two have joined forces,” said Pascal Pujol, MD, PhD, chair of SFMPP.

For Dr. Pujol, broadening the application of genome sequencing is a no-brainer. “It won’t be like in Gattaca,” he reassures us. “It wouldn’t be done to determine a person’s character but [rather] to prevent those rare diseases that affect 4 to 5% of the population.”

*A reference to Andrew Niccol’s 1997 science fiction movie Gattaca. The film is set in a futuristic world in which parents can choose the genotype of their children to conceive test-tube babies with the fewest defects and the most advantages possible for society.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

Will the traditional newborn screening program developed 60 years ago by Dr. Robert Guthrie soon be superseded by genome screening at birth? Routine sampling and analysis of newborn DNA would allow us to screen for many hundreds of childhood genetic diseases. This is the claim made by David Geneviève, MD, PhD, chair of the French Association of Clinical Geneticists and lecturer at the University of Montpellier (France), at the 9th annual conference of the French Society of Predictive and Personalized Medicine.

To date, newborn screening has consisted of taking a drop of blood from a newborn’s heel. In the future, DNA samples could be taken from babies for whole genome sequencing to look for diseases that are likely to crop up later in life.
 

The challenge

“In France, nearly all of the 720,000 babies born each year undergo newborn screening (only 300 refuse),” said Dr. Geneviève. For 60 years, newborn screening has tested for phenylketonuria, congenital hypothyroidism, congenital adrenal hyperplasia, sickle cell disease, cystic fibrosis, and medium-chain acyl-coenzyme A dehydrogenase deficiency.

On Jan. 1, 2023, France’s national newborn screening program added seven new diseases, bringing the number of rare diseases screened for to 13. The new diseases are homocystinuria, maple syrup urine disease, tyrosinemia type 1, isovaleric acidemia, glutaric aciduria type I, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, and carnitine deficiency.

“There aren’t just 13 childhood diseases,” continued Dr. Geneviève. “There are several hundred rare diseases, and genome sequencing tools allow us to broaden our screening capabilities. It’s inevitable that the ability to sequence your child’s genome at birth will become a possibility. It’s highly likely that within 10-15 years, all newborns will have their genome determined at birth for screening purposes.”

Current international trials

Genome sequencing has already been studied for several years in multiple countries. New York’s Guardian study requires all newborns taking part to undergo genome sequencing. “Our English-speaking colleagues use the genome to screen for childhood diseases that would benefit from treatment (235 can be treated) but also as a preventive measure and a way of providing early therapeutic education,” said Dr. Geneviève.

In 2016, American researchers launched the BabySeq Project, which was conducted at several sites (Boston, New York, Birmingham, Detroit, and Philadelphia). One of its aims is to assess the medical, psychological, and financial impact of screening via genome sequencing at birth, compared with conventional screening.

In North Carolina, 25,000 newborns took part in the Early Check study, a neonatal genetic screening project focusing on childhood spinal muscular atrophy, fragile X syndrome, and Duchenne muscular dystrophy.

In the United Kingdom, Genomics England seeks to assess the feasibility, benefits, and risks of whole genome sequencing as part of the Newborn Genomes Programme, an analysis of 100,000 newborn genomes. Projects are also underway in Belgium, Italy, and France (PeriGEN MED in Dijon).
 

Dijon’s specialist team

The conditions for considering neonatal screening of a disease are determined by the health care authorities in each country and vary greatly from one state to the next.

To date, in France, the only genetic screening authorized is for childhood spinal muscular atrophy via identification of an anomaly on SMN1. It has not yet been implemented, but a pilot study of its use is underway.

“If we are able to identify the 40 newborns affected by spinal muscular atrophy from birth, we can offer these patients gene therapy and stop them from dying at 1 or 2 years of age,” said Dr. Geneviève.

In the future, France should draw up a list of diseases for which genetic screening is useful, he added.

Although France’s initiative for genomic medicine, France Génomique 2025, does not envisage a neonatal genome sequencing screening program, a team in Dijon is studying several dozen genomes to determine the medical and financial benefits of such a program, explained Dr. Geneviève.
 

 

 

Ethical issues

Of course, this technological achievement raises ethical issues. “What do we do with the genetic data obtained at birth that won’t become apparent until adulthood, if we find a BRCA1 or BRCA2 variant in a newborn’s genome?” asked Dr. Genevieve.

Will the information obtained be stored somewhere? “This is a real issue,” he said. “The English have a national system. In their newborn screening program, when an infant grows into adulthood, he or she can have access to the genetic data.”

There is also a big risk that women will be pressured to undergo genetic testing during pregnancy. “No genome-related antenatal tests are carried out unless there are concerning ultrasound findings and only to look for particularly severe incurable diseases,” said Dr. Geneviève.
 

Not like Gattaca*

Financial obstacles should be quickly pushed aside. The cost of genome sequencing has decreased in the past few years. The first sequencing in 2003 cost close to $3 billion. Nowadays, it can be done for less than 1,000 € (just over $1,000).

Although neonatal genetic screening would enable us to limit the development of serious diseases, the decision to use such testing routinely must be made by society as a whole, Dr. Geneviève concluded.

“We often oppose preventive and personalized treatment strategies. Now the two have joined forces,” said Pascal Pujol, MD, PhD, chair of SFMPP.

For Dr. Pujol, broadening the application of genome sequencing is a no-brainer. “It won’t be like in Gattaca,” he reassures us. “It wouldn’t be done to determine a person’s character but [rather] to prevent those rare diseases that affect 4 to 5% of the population.”

*A reference to Andrew Niccol’s 1997 science fiction movie Gattaca. The film is set in a futuristic world in which parents can choose the genotype of their children to conceive test-tube babies with the fewest defects and the most advantages possible for society.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

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Commentary: Obesity, Pregnancy, and Adjuvant Chemotherapy in BC, December 2023

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Dr. Roesch scans the journals so you don't have to!

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308
Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals so you don't have to!
Dr. Roesch scans the journals so you don't have to!

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308
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Commentary: Obesity, Pregnancy, and Adjuvant Chemotherapy in BC, December 2023

Article Type
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Dr. Roesch scans the journals so you don't have to!

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308
Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals so you don't have to!
Dr. Roesch scans the journals so you don't have to!

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

Erin Roesch, MD
Obesity and other metabolic comorbidities (including glucose intolerance, hypertension, and dyslipidemia) have been associated with poorer prognosis among breast cancer patients.1 The underlying mechanisms for which obesity is linked to inferior breast cancer outcomes is complex and may also involve drug efficacy in these patients. Data from the ATAC trial showed that there was a higher risk for recurrence among patients with obesity who were receiving an aromatase inhibitor (AI) vs patients with a healthy body weight receiving an AI; however, patients receiving tamoxifen did not exhibit this difference.2 A Danish Breast Cancer Group cohort study including 13,230 postmenopausal patients with stage I-III hormone receptor–positive (HR+) breast cancer treated with AI investigated the association of body mass index with recurrence (Harborg et al). There was a significantly increased risk for recurrence among those patients with obesity (adjusted hazard ratio 1.18; 95% CI 1.01-1.37) and severe obesity (adjusted hazard ratio 1.32; 95% CI 1.08-1.62) vs patients with healthy body weight. These results highlight the importance of lifestyle interventions targeting obesity and metabolic factors in breast cancer patients and support future studies investigating optimal drug selection based on body composition.

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.3 HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.4 Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.5 However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

  1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
  2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
  3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
  4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
  5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308
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GLP-1 RAs tied to suboptimal bowel prep, repeat colonoscopy

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Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

 

 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

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Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

 

 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

 

 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

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More evidence of better outcomes with 120–mm Hg BP target

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Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

 

 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

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Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

 

 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

 

 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

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Commentary: JAK Inhibitors and Comorbidities in AD, December 2023

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Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
This mercifully brief report from Yosipovitch and colleagues describes how lebrikizumab improves itch and improves sleep very rapidly in patients with moderate to severe atopic dermatitis. This is not surprising, as we know that interleukin-13 inhibition is a very good way to treat atopic dermatitis, and we should expect itch and sleep to improve as atopic dermatitis gets better. The take-home message from this report is that the improvements in itch and sleep can occur very quickly, in just a few days.

Schlösser and colleagues provide a real-world report of 48 patients treated with upadacitinib for atopic dermatitis, many of whom had previously been treated with cyclosporine and dupilumab. The upbeat authors concluded, "Overall, adverse events were mostly well tolerated." Being a cynical, glass-is-half-empty kind of person, I wondered what that meant. Most patients (56%) reported adverse events, the most common being acne (25% of patients treated), nausea (13%), respiratory tract infections (10%), and herpes virus (8%). The herpes virus signal is not just a bit of a concern for me, but it also makes it hard for me to convince patients to take a Janus kinase (JAK) inhibitor, as when I even mention herpes, patients reply, often rather emphatically, "I don't want herpes!" I'll be encouraging patients to get vaccinated for shingles when starting them on JAK inhibitors.

Dupilumab seems to work great in real-life use. In Martinez-Cabriales and colleagues' study of 62 children age < 12 with atopic dermatitis, only four discontinued the treatment. One of these was a nonresponder who took only one injection and had flushing, and one of the other three discontinued because their skin had completely cleared.

When I saw the title of Rand and colleagues' article, "Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab Versus Dupilumab in Moderate-to-Severe Atopic Dermatitis," I thought, Oh, this is great — a head-to-head, long-term trial comparing lebrikizumab and dupilumab. I was disappointed to find that this was simply a retrospective analysis of data reported from different studies. The study found little difference in efficacy or safety of the two drugs. Both seem to be excellent medications for atopic dermatitis.

Here's another study (Zhou et al) that reports possible increased risk for a comorbidity (cognitive dysfunction) associated with atopic dermatitis. This study reports that there is an elevated hazard ratio that is statistically significant; the article fails to report what the increased absolute risk is for cognitive dysfunction associated with atopic dermatitis. My guess is that it is small and probably clinically unimportant. The hazard ratio for developing dementia was 1.16. It's hard to know how that translates into absolute risk, but my brilliant friend and former partner, Dr Alan Fleischer, once told me that the odds ratio for smoking and lung cancer is something like 100; the hazard ratio is in the range of 20. On the basis of a hazard ratio of 1.16, I don't think patients with atopic dermatitis need to be any more worried about dementia than those without. (Though, to be honest, I think we can all be worried about developing dementia.)

In this tour de force analysis of 83 trials with over 20,000 participants, Drucker and colleagues determined that high doses of abrocitinib and upadacitinib are more effective than even dupilumab for atopic dermatitis. The standard doses of these JAK inhibitors were similar in efficacy to dupilumab. I think it's safe to say that JAK inhibitors are, at least at their high doses, more effective than dupilumab, but safety remains a critical factor in treatment decision-making. I think JAK inhibitors are a great option for patients who need the most effective treatment or who fail to respond to dupilumab.

The title of the article by Oh and colleagues, "Increased Risk of Renal Malignancy in Patients With Moderate to Severe Atopic Dermatitis," seems like it could terrify patients. The study involved an analysis of an enormous number of people, including tens of thousands with atopic dermatitis and millions of controls. The investigators did find statistically significant differences in the rate of malignancy. The rate of renal cancer was about 1.6 per 10,000 person-years for people without atopic dermatitis or people with mild atopic dermatitis; the rate was about 2.5 per 10,000 people for patients with moderate to severe atopic dermatitis. While the rate of renal cancer was statistically significantly higher in patients with moderate to severe atopic dermatitis (ie, the higher rate was unlikely to be occurring due to chance alone), these patients have very little risk for renal malignancy. The authors' conclusion that regular checkups for renal malignancy are recommended for patients with severe atopic dermatitis seems unnecessary to me.

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Professor of Dermatology, Pathology and Social Sciences & Health Policy Wake Forest University School of Medicine, Winston-Salem, NC
 

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Dr. Feldman scans the journals, so you don’t have to!
Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
This mercifully brief report from Yosipovitch and colleagues describes how lebrikizumab improves itch and improves sleep very rapidly in patients with moderate to severe atopic dermatitis. This is not surprising, as we know that interleukin-13 inhibition is a very good way to treat atopic dermatitis, and we should expect itch and sleep to improve as atopic dermatitis gets better. The take-home message from this report is that the improvements in itch and sleep can occur very quickly, in just a few days.

Schlösser and colleagues provide a real-world report of 48 patients treated with upadacitinib for atopic dermatitis, many of whom had previously been treated with cyclosporine and dupilumab. The upbeat authors concluded, "Overall, adverse events were mostly well tolerated." Being a cynical, glass-is-half-empty kind of person, I wondered what that meant. Most patients (56%) reported adverse events, the most common being acne (25% of patients treated), nausea (13%), respiratory tract infections (10%), and herpes virus (8%). The herpes virus signal is not just a bit of a concern for me, but it also makes it hard for me to convince patients to take a Janus kinase (JAK) inhibitor, as when I even mention herpes, patients reply, often rather emphatically, "I don't want herpes!" I'll be encouraging patients to get vaccinated for shingles when starting them on JAK inhibitors.

Dupilumab seems to work great in real-life use. In Martinez-Cabriales and colleagues' study of 62 children age < 12 with atopic dermatitis, only four discontinued the treatment. One of these was a nonresponder who took only one injection and had flushing, and one of the other three discontinued because their skin had completely cleared.

When I saw the title of Rand and colleagues' article, "Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab Versus Dupilumab in Moderate-to-Severe Atopic Dermatitis," I thought, Oh, this is great — a head-to-head, long-term trial comparing lebrikizumab and dupilumab. I was disappointed to find that this was simply a retrospective analysis of data reported from different studies. The study found little difference in efficacy or safety of the two drugs. Both seem to be excellent medications for atopic dermatitis.

Here's another study (Zhou et al) that reports possible increased risk for a comorbidity (cognitive dysfunction) associated with atopic dermatitis. This study reports that there is an elevated hazard ratio that is statistically significant; the article fails to report what the increased absolute risk is for cognitive dysfunction associated with atopic dermatitis. My guess is that it is small and probably clinically unimportant. The hazard ratio for developing dementia was 1.16. It's hard to know how that translates into absolute risk, but my brilliant friend and former partner, Dr Alan Fleischer, once told me that the odds ratio for smoking and lung cancer is something like 100; the hazard ratio is in the range of 20. On the basis of a hazard ratio of 1.16, I don't think patients with atopic dermatitis need to be any more worried about dementia than those without. (Though, to be honest, I think we can all be worried about developing dementia.)

In this tour de force analysis of 83 trials with over 20,000 participants, Drucker and colleagues determined that high doses of abrocitinib and upadacitinib are more effective than even dupilumab for atopic dermatitis. The standard doses of these JAK inhibitors were similar in efficacy to dupilumab. I think it's safe to say that JAK inhibitors are, at least at their high doses, more effective than dupilumab, but safety remains a critical factor in treatment decision-making. I think JAK inhibitors are a great option for patients who need the most effective treatment or who fail to respond to dupilumab.

The title of the article by Oh and colleagues, "Increased Risk of Renal Malignancy in Patients With Moderate to Severe Atopic Dermatitis," seems like it could terrify patients. The study involved an analysis of an enormous number of people, including tens of thousands with atopic dermatitis and millions of controls. The investigators did find statistically significant differences in the rate of malignancy. The rate of renal cancer was about 1.6 per 10,000 person-years for people without atopic dermatitis or people with mild atopic dermatitis; the rate was about 2.5 per 10,000 people for patients with moderate to severe atopic dermatitis. While the rate of renal cancer was statistically significantly higher in patients with moderate to severe atopic dermatitis (ie, the higher rate was unlikely to be occurring due to chance alone), these patients have very little risk for renal malignancy. The authors' conclusion that regular checkups for renal malignancy are recommended for patients with severe atopic dermatitis seems unnecessary to me.

Steven R. Feldman, MD, PhD
This mercifully brief report from Yosipovitch and colleagues describes how lebrikizumab improves itch and improves sleep very rapidly in patients with moderate to severe atopic dermatitis. This is not surprising, as we know that interleukin-13 inhibition is a very good way to treat atopic dermatitis, and we should expect itch and sleep to improve as atopic dermatitis gets better. The take-home message from this report is that the improvements in itch and sleep can occur very quickly, in just a few days.

Schlösser and colleagues provide a real-world report of 48 patients treated with upadacitinib for atopic dermatitis, many of whom had previously been treated with cyclosporine and dupilumab. The upbeat authors concluded, "Overall, adverse events were mostly well tolerated." Being a cynical, glass-is-half-empty kind of person, I wondered what that meant. Most patients (56%) reported adverse events, the most common being acne (25% of patients treated), nausea (13%), respiratory tract infections (10%), and herpes virus (8%). The herpes virus signal is not just a bit of a concern for me, but it also makes it hard for me to convince patients to take a Janus kinase (JAK) inhibitor, as when I even mention herpes, patients reply, often rather emphatically, "I don't want herpes!" I'll be encouraging patients to get vaccinated for shingles when starting them on JAK inhibitors.

Dupilumab seems to work great in real-life use. In Martinez-Cabriales and colleagues' study of 62 children age < 12 with atopic dermatitis, only four discontinued the treatment. One of these was a nonresponder who took only one injection and had flushing, and one of the other three discontinued because their skin had completely cleared.

When I saw the title of Rand and colleagues' article, "Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab Versus Dupilumab in Moderate-to-Severe Atopic Dermatitis," I thought, Oh, this is great — a head-to-head, long-term trial comparing lebrikizumab and dupilumab. I was disappointed to find that this was simply a retrospective analysis of data reported from different studies. The study found little difference in efficacy or safety of the two drugs. Both seem to be excellent medications for atopic dermatitis.

Here's another study (Zhou et al) that reports possible increased risk for a comorbidity (cognitive dysfunction) associated with atopic dermatitis. This study reports that there is an elevated hazard ratio that is statistically significant; the article fails to report what the increased absolute risk is for cognitive dysfunction associated with atopic dermatitis. My guess is that it is small and probably clinically unimportant. The hazard ratio for developing dementia was 1.16. It's hard to know how that translates into absolute risk, but my brilliant friend and former partner, Dr Alan Fleischer, once told me that the odds ratio for smoking and lung cancer is something like 100; the hazard ratio is in the range of 20. On the basis of a hazard ratio of 1.16, I don't think patients with atopic dermatitis need to be any more worried about dementia than those without. (Though, to be honest, I think we can all be worried about developing dementia.)

In this tour de force analysis of 83 trials with over 20,000 participants, Drucker and colleagues determined that high doses of abrocitinib and upadacitinib are more effective than even dupilumab for atopic dermatitis. The standard doses of these JAK inhibitors were similar in efficacy to dupilumab. I think it's safe to say that JAK inhibitors are, at least at their high doses, more effective than dupilumab, but safety remains a critical factor in treatment decision-making. I think JAK inhibitors are a great option for patients who need the most effective treatment or who fail to respond to dupilumab.

The title of the article by Oh and colleagues, "Increased Risk of Renal Malignancy in Patients With Moderate to Severe Atopic Dermatitis," seems like it could terrify patients. The study involved an analysis of an enormous number of people, including tens of thousands with atopic dermatitis and millions of controls. The investigators did find statistically significant differences in the rate of malignancy. The rate of renal cancer was about 1.6 per 10,000 person-years for people without atopic dermatitis or people with mild atopic dermatitis; the rate was about 2.5 per 10,000 people for patients with moderate to severe atopic dermatitis. While the rate of renal cancer was statistically significantly higher in patients with moderate to severe atopic dermatitis (ie, the higher rate was unlikely to be occurring due to chance alone), these patients have very little risk for renal malignancy. The authors' conclusion that regular checkups for renal malignancy are recommended for patients with severe atopic dermatitis seems unnecessary to me.

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Do patients follow up on referrals after telehealth visits?

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Telehealth has been a boon for modern-day patients, allowing people who might have difficulty accessing in-person appointments to continue seeing their physicians. But how many patients actually follow through on their physician’s recommendations afterward?

A new study suggests that many patients don’t complete recommended diagnostic tests or specialist referrals after appointments with their primary care physicians, especially when those appointments take place via telehealth.

Investigators retrospectively examined test and referral orders for more than 4,000 patients to see how many complied with recommendations to have a colonoscopy, consult a dermatologist for a suspicious skin lesion, or undergo a cardiac stress test.

Completion of a recommended test or specialty referral was termed “diagnostic loop closure.” In particular, the researchers wanted to compare loop closure after telehealth versus in-person visits.

Rates of loop closure were low across all visit modalities but were lower for tests and referrals ordered during telehealth visits, compared with in-person visits – especially for colonoscopies.

“The take-home message for practicing clinicians is that they should be especially aware of follow-up for tests or referrals ordered during telehealth visits,” said corresponding author Maëlys Amat, MD, MBA, a primary care physician at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston.

The study was published online on in JAMA Network Open.
 

‘Unintended side effects’

“Diagnostic errors present a huge safety concern, impacting many patient lives and costing the health care system billions of dollars, said Dr. Amat, who is also an instructor at Harvard Medical School.

“Telehealth utilization increased rapidly during the COVID pandemic, and although there are clear benefits to utilizing telehealth, our team sought to investigate unintended side effects of this technology and highlight opportunities for improvement,” she said.

To investigate the question, the researchers reviewed medical records of 4,113 patients, with a mean age of 59 years, at two Boston-based primary care sites: an urban hospital–based primary care practice and an affiliated community health center.



Orders for tests or referrals in both centers were placed electronically through the medical record. During an in-person visit, the patient was handed a form with a phone number to call to schedule the test or referral. Patients with limited English proficiency or complex needs may have received help with the scheduling the referral during check-out.

For telehealth visits, the clinician gave the patient the phone number to call to schedule the test or referral during the visit itself. In all scenarios, patients did not receive communication after the visit reminding them about the referral or test.

A loop was considered “closed” if the orders were completed within 365 days, 90 days, or 45 days for colonoscopy, dermatology visits, or cardiac stress testing, respectively.

Of the tests, 52.4% were ordered during an in-person visit, 27.8% were ordered during a telehealth visit, and 19.7% were ordered without a visit.

Tracking systems, virtual checkout

Fewer than half of the orders (42.6%) placed during a telehealth visit were completed within the designated time frame, compared with 58.4% of the orders placed during an in-person visit and 57.4% placed without a visit.

Patients who had telehealth visits were roughly half as likely as those who had in-person visits to close the loop on high-risk tests and referrals, even in an analysis that adjusted for test type, patient demographic characteristics, comorbidities, clinical site, clinician type, and patient engagement (odds ratio, 0.55; 95% confidence interval, 0.47-0.64).

Only 39.8% of colonoscopy referrals ordered during a telehealth visit were completed during the 365-day time period, compared with 56.9% ordered during an in-person visit and 56.7% ordered without a visit.

Follow-through with dermatology referrals within 90 days was roughly the same across all types of visits (63.1% for telehealth, 61.5% for in-person, and 62.9% for no visit). No significant differences were found between telehealth and in-person visits or orders placed without a visit.

Although patients seen via telehealth were less likely than those seen in person to follow through on cardiac stress tests within the 45-day window (59.1% vs. 63.2%), this difference didn’t reach statistical significance.

“Ideally, clinicians would implement automatic tracking systems to help ensure that an ordered test or referral is completed,” Dr. Amat commented. “However, if these systems aren’t yet in place, we strongly encourage clinicians to create their own work flows for tracking tests to completion.”

Additionally, “clinicians should consider implementing a virtual checkout system, similar to what is done during in-person visits, to help patients better understand recommended next steps,” she continued.

Other potentially helpful ways to improve loop closure include automatic tracking for outstanding tests, interventions such as telephone outreach to patients, automated text and email reminders, and the use of referral managers – especially in remote, rural areas or for “disadvantaged patients with limited health care access and literacy.”
 

 

 

Education is key

Kisha Davis, MD, MPH, member of the board of directors of the American Academy of Family Physicians, said in an interview that being able to see a provider virtually can make the difference between a person receiving or not receiving medical care. She regards telehealth as another tool in the toolkit her practice offers to provide comprehensive health care.

Dr. Davis, a family physician in Gaithersburg, Md., who wasn’t involved with the study, described a patient with hypertension who was an Uber driver. “During the pandemic, Uber rides were down, and he couldn›t afford to pass up any opportunities, so he pulled over to the side of the road after one of his rides, did his telehealth visit, reviewed his medications, and went on to his next ride.”

The key is to make sure that patients receive adequate follow-up from the office, which Dr. Davis arranged for this patient.

She noted that telehealth “is best done if there’s an established physician-patient relationship but harder to accomplish successfully if you’ve only met the patient on telehealth and never in person.”

The study didn’t specify whether the physicians had an established relationship with their patients.

During the checkout process after an in-person appointment, patients often receive a sheet of paper with the follow-up referrals. “I can see where patients are less likely to follow through if they don’t have someone handing them that paper,” she said.

In her practice, patients’ charts are color-coded “to keep track and make sure it’s not just the ‘squeaky wheels’ that get all the attention,” she said. “The onus is on the physician and the practice, in today’s world of value-based care, to make sure that patients who don’t come into the office are getting the care they need.”

This is facilitated by a “system of care coordination” in which the office team – such as a nurse or medical assistant – follows up with patients to see if they’ve “gotten everything done without barriers,” Dr. Davis said. “Did they have trouble filling that prescription? Did they have difficulty with the referral? Or do they not think it’s necessary – for example, a patient might not go to physical therapy because the injury has improved.”

Dr. Davis wasn’t surprised that patients were less likely to close the loop for colonoscopies compared with seeking out a stress test or treatment for skin lesions.

“People who have a skin lesion may be concerned about their appearance or about skin cancer, and people who need a stress test may have had cardiac symptoms or be worried about their heart.” But a routine screening such as a colonoscopy may not mobilize the patient’s concern to the same degree.

“Additionally, a colonoscopy has an ‘ick factor,’ so there aren’t a whole lot of people who are jumping to have the procedure done.” She suggested considering newer FDA-approved stool tests to screen for colon cancer.

Dr. Amat and Dr. Davis both emphasized that educating patients – both during and after the visit – and making sure they understand the importance of their referral for tests or specialists referrals are key to ensuring that they follow through on the recommendations.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Amat was supported by the Arnold Tofias and Leo Condakes Quality Scholarship Program. Dr. Amat declared no relevant financial relationships. Dr. Davis is the chief health officer for Montgomery County in Maryland.

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

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Telehealth has been a boon for modern-day patients, allowing people who might have difficulty accessing in-person appointments to continue seeing their physicians. But how many patients actually follow through on their physician’s recommendations afterward?

A new study suggests that many patients don’t complete recommended diagnostic tests or specialist referrals after appointments with their primary care physicians, especially when those appointments take place via telehealth.

Investigators retrospectively examined test and referral orders for more than 4,000 patients to see how many complied with recommendations to have a colonoscopy, consult a dermatologist for a suspicious skin lesion, or undergo a cardiac stress test.

Completion of a recommended test or specialty referral was termed “diagnostic loop closure.” In particular, the researchers wanted to compare loop closure after telehealth versus in-person visits.

Rates of loop closure were low across all visit modalities but were lower for tests and referrals ordered during telehealth visits, compared with in-person visits – especially for colonoscopies.

“The take-home message for practicing clinicians is that they should be especially aware of follow-up for tests or referrals ordered during telehealth visits,” said corresponding author Maëlys Amat, MD, MBA, a primary care physician at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston.

The study was published online on in JAMA Network Open.
 

‘Unintended side effects’

“Diagnostic errors present a huge safety concern, impacting many patient lives and costing the health care system billions of dollars, said Dr. Amat, who is also an instructor at Harvard Medical School.

“Telehealth utilization increased rapidly during the COVID pandemic, and although there are clear benefits to utilizing telehealth, our team sought to investigate unintended side effects of this technology and highlight opportunities for improvement,” she said.

To investigate the question, the researchers reviewed medical records of 4,113 patients, with a mean age of 59 years, at two Boston-based primary care sites: an urban hospital–based primary care practice and an affiliated community health center.



Orders for tests or referrals in both centers were placed electronically through the medical record. During an in-person visit, the patient was handed a form with a phone number to call to schedule the test or referral. Patients with limited English proficiency or complex needs may have received help with the scheduling the referral during check-out.

For telehealth visits, the clinician gave the patient the phone number to call to schedule the test or referral during the visit itself. In all scenarios, patients did not receive communication after the visit reminding them about the referral or test.

A loop was considered “closed” if the orders were completed within 365 days, 90 days, or 45 days for colonoscopy, dermatology visits, or cardiac stress testing, respectively.

Of the tests, 52.4% were ordered during an in-person visit, 27.8% were ordered during a telehealth visit, and 19.7% were ordered without a visit.

Tracking systems, virtual checkout

Fewer than half of the orders (42.6%) placed during a telehealth visit were completed within the designated time frame, compared with 58.4% of the orders placed during an in-person visit and 57.4% placed without a visit.

Patients who had telehealth visits were roughly half as likely as those who had in-person visits to close the loop on high-risk tests and referrals, even in an analysis that adjusted for test type, patient demographic characteristics, comorbidities, clinical site, clinician type, and patient engagement (odds ratio, 0.55; 95% confidence interval, 0.47-0.64).

Only 39.8% of colonoscopy referrals ordered during a telehealth visit were completed during the 365-day time period, compared with 56.9% ordered during an in-person visit and 56.7% ordered without a visit.

Follow-through with dermatology referrals within 90 days was roughly the same across all types of visits (63.1% for telehealth, 61.5% for in-person, and 62.9% for no visit). No significant differences were found between telehealth and in-person visits or orders placed without a visit.

Although patients seen via telehealth were less likely than those seen in person to follow through on cardiac stress tests within the 45-day window (59.1% vs. 63.2%), this difference didn’t reach statistical significance.

“Ideally, clinicians would implement automatic tracking systems to help ensure that an ordered test or referral is completed,” Dr. Amat commented. “However, if these systems aren’t yet in place, we strongly encourage clinicians to create their own work flows for tracking tests to completion.”

Additionally, “clinicians should consider implementing a virtual checkout system, similar to what is done during in-person visits, to help patients better understand recommended next steps,” she continued.

Other potentially helpful ways to improve loop closure include automatic tracking for outstanding tests, interventions such as telephone outreach to patients, automated text and email reminders, and the use of referral managers – especially in remote, rural areas or for “disadvantaged patients with limited health care access and literacy.”
 

 

 

Education is key

Kisha Davis, MD, MPH, member of the board of directors of the American Academy of Family Physicians, said in an interview that being able to see a provider virtually can make the difference between a person receiving or not receiving medical care. She regards telehealth as another tool in the toolkit her practice offers to provide comprehensive health care.

Dr. Davis, a family physician in Gaithersburg, Md., who wasn’t involved with the study, described a patient with hypertension who was an Uber driver. “During the pandemic, Uber rides were down, and he couldn›t afford to pass up any opportunities, so he pulled over to the side of the road after one of his rides, did his telehealth visit, reviewed his medications, and went on to his next ride.”

The key is to make sure that patients receive adequate follow-up from the office, which Dr. Davis arranged for this patient.

She noted that telehealth “is best done if there’s an established physician-patient relationship but harder to accomplish successfully if you’ve only met the patient on telehealth and never in person.”

The study didn’t specify whether the physicians had an established relationship with their patients.

During the checkout process after an in-person appointment, patients often receive a sheet of paper with the follow-up referrals. “I can see where patients are less likely to follow through if they don’t have someone handing them that paper,” she said.

In her practice, patients’ charts are color-coded “to keep track and make sure it’s not just the ‘squeaky wheels’ that get all the attention,” she said. “The onus is on the physician and the practice, in today’s world of value-based care, to make sure that patients who don’t come into the office are getting the care they need.”

This is facilitated by a “system of care coordination” in which the office team – such as a nurse or medical assistant – follows up with patients to see if they’ve “gotten everything done without barriers,” Dr. Davis said. “Did they have trouble filling that prescription? Did they have difficulty with the referral? Or do they not think it’s necessary – for example, a patient might not go to physical therapy because the injury has improved.”

Dr. Davis wasn’t surprised that patients were less likely to close the loop for colonoscopies compared with seeking out a stress test or treatment for skin lesions.

“People who have a skin lesion may be concerned about their appearance or about skin cancer, and people who need a stress test may have had cardiac symptoms or be worried about their heart.” But a routine screening such as a colonoscopy may not mobilize the patient’s concern to the same degree.

“Additionally, a colonoscopy has an ‘ick factor,’ so there aren’t a whole lot of people who are jumping to have the procedure done.” She suggested considering newer FDA-approved stool tests to screen for colon cancer.

Dr. Amat and Dr. Davis both emphasized that educating patients – both during and after the visit – and making sure they understand the importance of their referral for tests or specialists referrals are key to ensuring that they follow through on the recommendations.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Amat was supported by the Arnold Tofias and Leo Condakes Quality Scholarship Program. Dr. Amat declared no relevant financial relationships. Dr. Davis is the chief health officer for Montgomery County in Maryland.

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

Telehealth has been a boon for modern-day patients, allowing people who might have difficulty accessing in-person appointments to continue seeing their physicians. But how many patients actually follow through on their physician’s recommendations afterward?

A new study suggests that many patients don’t complete recommended diagnostic tests or specialist referrals after appointments with their primary care physicians, especially when those appointments take place via telehealth.

Investigators retrospectively examined test and referral orders for more than 4,000 patients to see how many complied with recommendations to have a colonoscopy, consult a dermatologist for a suspicious skin lesion, or undergo a cardiac stress test.

Completion of a recommended test or specialty referral was termed “diagnostic loop closure.” In particular, the researchers wanted to compare loop closure after telehealth versus in-person visits.

Rates of loop closure were low across all visit modalities but were lower for tests and referrals ordered during telehealth visits, compared with in-person visits – especially for colonoscopies.

“The take-home message for practicing clinicians is that they should be especially aware of follow-up for tests or referrals ordered during telehealth visits,” said corresponding author Maëlys Amat, MD, MBA, a primary care physician at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston.

The study was published online on in JAMA Network Open.
 

‘Unintended side effects’

“Diagnostic errors present a huge safety concern, impacting many patient lives and costing the health care system billions of dollars, said Dr. Amat, who is also an instructor at Harvard Medical School.

“Telehealth utilization increased rapidly during the COVID pandemic, and although there are clear benefits to utilizing telehealth, our team sought to investigate unintended side effects of this technology and highlight opportunities for improvement,” she said.

To investigate the question, the researchers reviewed medical records of 4,113 patients, with a mean age of 59 years, at two Boston-based primary care sites: an urban hospital–based primary care practice and an affiliated community health center.



Orders for tests or referrals in both centers were placed electronically through the medical record. During an in-person visit, the patient was handed a form with a phone number to call to schedule the test or referral. Patients with limited English proficiency or complex needs may have received help with the scheduling the referral during check-out.

For telehealth visits, the clinician gave the patient the phone number to call to schedule the test or referral during the visit itself. In all scenarios, patients did not receive communication after the visit reminding them about the referral or test.

A loop was considered “closed” if the orders were completed within 365 days, 90 days, or 45 days for colonoscopy, dermatology visits, or cardiac stress testing, respectively.

Of the tests, 52.4% were ordered during an in-person visit, 27.8% were ordered during a telehealth visit, and 19.7% were ordered without a visit.

Tracking systems, virtual checkout

Fewer than half of the orders (42.6%) placed during a telehealth visit were completed within the designated time frame, compared with 58.4% of the orders placed during an in-person visit and 57.4% placed without a visit.

Patients who had telehealth visits were roughly half as likely as those who had in-person visits to close the loop on high-risk tests and referrals, even in an analysis that adjusted for test type, patient demographic characteristics, comorbidities, clinical site, clinician type, and patient engagement (odds ratio, 0.55; 95% confidence interval, 0.47-0.64).

Only 39.8% of colonoscopy referrals ordered during a telehealth visit were completed during the 365-day time period, compared with 56.9% ordered during an in-person visit and 56.7% ordered without a visit.

Follow-through with dermatology referrals within 90 days was roughly the same across all types of visits (63.1% for telehealth, 61.5% for in-person, and 62.9% for no visit). No significant differences were found between telehealth and in-person visits or orders placed without a visit.

Although patients seen via telehealth were less likely than those seen in person to follow through on cardiac stress tests within the 45-day window (59.1% vs. 63.2%), this difference didn’t reach statistical significance.

“Ideally, clinicians would implement automatic tracking systems to help ensure that an ordered test or referral is completed,” Dr. Amat commented. “However, if these systems aren’t yet in place, we strongly encourage clinicians to create their own work flows for tracking tests to completion.”

Additionally, “clinicians should consider implementing a virtual checkout system, similar to what is done during in-person visits, to help patients better understand recommended next steps,” she continued.

Other potentially helpful ways to improve loop closure include automatic tracking for outstanding tests, interventions such as telephone outreach to patients, automated text and email reminders, and the use of referral managers – especially in remote, rural areas or for “disadvantaged patients with limited health care access and literacy.”
 

 

 

Education is key

Kisha Davis, MD, MPH, member of the board of directors of the American Academy of Family Physicians, said in an interview that being able to see a provider virtually can make the difference between a person receiving or not receiving medical care. She regards telehealth as another tool in the toolkit her practice offers to provide comprehensive health care.

Dr. Davis, a family physician in Gaithersburg, Md., who wasn’t involved with the study, described a patient with hypertension who was an Uber driver. “During the pandemic, Uber rides were down, and he couldn›t afford to pass up any opportunities, so he pulled over to the side of the road after one of his rides, did his telehealth visit, reviewed his medications, and went on to his next ride.”

The key is to make sure that patients receive adequate follow-up from the office, which Dr. Davis arranged for this patient.

She noted that telehealth “is best done if there’s an established physician-patient relationship but harder to accomplish successfully if you’ve only met the patient on telehealth and never in person.”

The study didn’t specify whether the physicians had an established relationship with their patients.

During the checkout process after an in-person appointment, patients often receive a sheet of paper with the follow-up referrals. “I can see where patients are less likely to follow through if they don’t have someone handing them that paper,” she said.

In her practice, patients’ charts are color-coded “to keep track and make sure it’s not just the ‘squeaky wheels’ that get all the attention,” she said. “The onus is on the physician and the practice, in today’s world of value-based care, to make sure that patients who don’t come into the office are getting the care they need.”

This is facilitated by a “system of care coordination” in which the office team – such as a nurse or medical assistant – follows up with patients to see if they’ve “gotten everything done without barriers,” Dr. Davis said. “Did they have trouble filling that prescription? Did they have difficulty with the referral? Or do they not think it’s necessary – for example, a patient might not go to physical therapy because the injury has improved.”

Dr. Davis wasn’t surprised that patients were less likely to close the loop for colonoscopies compared with seeking out a stress test or treatment for skin lesions.

“People who have a skin lesion may be concerned about their appearance or about skin cancer, and people who need a stress test may have had cardiac symptoms or be worried about their heart.” But a routine screening such as a colonoscopy may not mobilize the patient’s concern to the same degree.

“Additionally, a colonoscopy has an ‘ick factor,’ so there aren’t a whole lot of people who are jumping to have the procedure done.” She suggested considering newer FDA-approved stool tests to screen for colon cancer.

Dr. Amat and Dr. Davis both emphasized that educating patients – both during and after the visit – and making sure they understand the importance of their referral for tests or specialists referrals are key to ensuring that they follow through on the recommendations.

The study was funded by the Agency for Healthcare Research and Quality. Dr. Amat was supported by the Arnold Tofias and Leo Condakes Quality Scholarship Program. Dr. Amat declared no relevant financial relationships. Dr. Davis is the chief health officer for Montgomery County in Maryland.

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

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