It is no secret that the COVID-19 pandemic resulted in widespread disruptions in health care services. While providers and resources were limited and many patients were apprehensive to present to health care settings out of concern of disease contraction, telehealth services did offer some relief.

Compared to other specialty care services, mental health care providers were well equipped to handle the expansion of telehealth services, as extensive treatment literature provides strong support for the use of psychotherapeutic interventions over telehealth mediums.¹ This holds true in the context of obsessive-compulsive disorder (OCD), where an impressive literature supports the use of telehealth delivery for the gold-standard psychotherapeutic, exposure and response prevention (ERP).^2,3,4

Through ERP, patients work with a clinician to systematically expose themselves to anxiety-providing triggers while actively resisting compulsive behaviors to learn the distress does go away with time and/or the distress is within their ability to cope. This intervention is conceptually similar to repeatedly watching a scary film, by which continued exposure results in less pronounced emotional reaction with subsequent viewings.

Fortunately for patients and providers, the expansion of telehealth ERP across different treatment settings has had many unintended benefits, including increased access to care, lower no-show rates due to the ease of attending appointments, and the ability to offer higher levels of care, including intensive outpatient programs, over telehealth mediums. Anecdotally, our clinic has been able to increase patient reach by providing telehealth ERP to those who historically would not have been able to access care due to geography. Even for those living within driving distance to our clinic, the ease of joining a video visit for a 45-minute appointment far outweighs driving into the clinic, in many circumstances. With these benefits, the delivery of ERP over telehealth appears likely to stay, although OCD providers delivering ERP will need to consider when and for whom this medium may not be appropriate.

To this end, we recently conducted a study examining ERP providers perceptions of telehealth and in-person ERP, patient characteristics best suited for telehealth services, and provider ability to identify and address factors that adversely impact the course of treatment (e.g., substance use, limited symptom insight, distractions during ERP, etc.).⁵ Providers reported lower feasibility ratings for telehealth compared to in-person ERP for younger patients (aged under 13 years), and patients with more severe OCD presentations. Providers also reported more difficulty identifying and addressing ERP interfering factors over telehealth relative to in-person. The findings from our research do not necessarily speak to the effectiveness of telehealth ERP, which has repeatedly been documented in treatment literature, but rather our findings highlight that ERP providers endorse reservations about the feasibility of ERP for certain OCD patient profiles, and that telehealth ERP may not be appropriate for all patients with OCD.

Mental health care providers, including those delivering ERP, should consider when telehealth is and is not appropriate. Importantly, telehealth offers a limited field of view compared to in-person, and providers can only observe what is captured by the camera. In the context of telehealth ERP, patients may engage in subtle avoidant behaviors that are more difficult to observe, which may prevent them from experiencing necessary anxiety during exposure practice. Many providers may have firsthand experience with this, or patients who appear distracted over telehealth mediums because of environmental factors that can be controlled for during in-person services.

As telehealth treatment options appear increasingly likely to stay, ERP providers and intervention researchers should continue identifying patient characteristics that are more and less appropriate for telehealth settings in order to maximize treatment outcomes. Providers should share concerns with patients when delivering telehealth ERP and work to address interfering factors impacting the course of treatment. In circumstances where this is not possible, such as when the patients age or symptom severity prevents effective telehealth ERP, or when treatment progress stalls, providers should speak with patients to determine if it would be beneficial to transition to in-person services.

Both in-person and telehealth ERP are fundamentally the same, however it does appear that subtle differences across these modalities may have differential impacts on treatment outcomes for certain OCD patient presentations. Telehealth ERP, and more broadly telehealth psychotherapy, offers many benefits for patients and providers, however appropriate caution should be exhibited, and providers should use clinical judgment when offering telehealth services.

Dr. Wiese is a clinical psychologist in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, Texas. He is primarily focused on conducting research on OCD and related disorders and providing empirically supported treatments to individuals diagnosed with these conditions.

References

1. Fernandez E et al. Live psychotherapy by video versus in‐person: A meta‐analysis of efficacy and its relationship to types and targets of treatment. Clin Psychol Psychother. 2021 Nov;28(6):1535-49. doi: 10.1002/cpp.2594.

2. Storch EA et al. Preliminary investigation of web-camera delivered cognitive-behavioral therapy for youth with obsessive-compulsive disorder. Psychiatry Res. 2011 Oct 30;189(3):407-12. doi: 10.1016/j.psychres.2011.05.047.

3. Fletcher TL et al. A pilot open trial of video telehealth-delivered exposure and response prevention for obsessive-compulsive disorder in rural Veterans. Mil Psychol. 2021 Oct 28;34(1):83-90. doi: 10.1080/08995605.2021.1970983.

4. Wootton BM. Remote cognitive–behavior therapy for obsessive–compulsive symptoms: a meta-analysis. Clin Psychol Rev. 2016 Feb;43:103-13. doi: 10.1016/j.cpr.2015.10.001.

5. Wiese AD et al. Provider perceptions of telehealth and in-person exposure and response prevention for obsessive–compulsive disorder. Psychiatry Res. 2022 Jul;313:114610. doi: 10.1016/j.psychres.2022.114610.

It is no secret that the COVID-19 pandemic resulted in widespread disruptions in health care services. While providers and resources were limited and many patients were apprehensive to present to health care settings out of concern of disease contraction, telehealth services did offer some relief.

Compared to other specialty care services, mental health care providers were well equipped to handle the expansion of telehealth services, as extensive treatment literature provides strong support for the use of psychotherapeutic interventions over telehealth mediums.¹ This holds true in the context of obsessive-compulsive disorder (OCD), where an impressive literature supports the use of telehealth delivery for the gold-standard psychotherapeutic, exposure and response prevention (ERP).^2,3,4

Through ERP, patients work with a clinician to systematically expose themselves to anxiety-providing triggers while actively resisting compulsive behaviors to learn the distress does go away with time and/or the distress is within their ability to cope. This intervention is conceptually similar to repeatedly watching a scary film, by which continued exposure results in less pronounced emotional reaction with subsequent viewings.

Fortunately for patients and providers, the expansion of telehealth ERP across different treatment settings has had many unintended benefits, including increased access to care, lower no-show rates due to the ease of attending appointments, and the ability to offer higher levels of care, including intensive outpatient programs, over telehealth mediums. Anecdotally, our clinic has been able to increase patient reach by providing telehealth ERP to those who historically would not have been able to access care due to geography. Even for those living within driving distance to our clinic, the ease of joining a video visit for a 45-minute appointment far outweighs driving into the clinic, in many circumstances. With these benefits, the delivery of ERP over telehealth appears likely to stay, although OCD providers delivering ERP will need to consider when and for whom this medium may not be appropriate.

To this end, we recently conducted a study examining ERP providers perceptions of telehealth and in-person ERP, patient characteristics best suited for telehealth services, and provider ability to identify and address factors that adversely impact the course of treatment (e.g., substance use, limited symptom insight, distractions during ERP, etc.).⁵ Providers reported lower feasibility ratings for telehealth compared to in-person ERP for younger patients (aged under 13 years), and patients with more severe OCD presentations. Providers also reported more difficulty identifying and addressing ERP interfering factors over telehealth relative to in-person. The findings from our research do not necessarily speak to the effectiveness of telehealth ERP, which has repeatedly been documented in treatment literature, but rather our findings highlight that ERP providers endorse reservations about the feasibility of ERP for certain OCD patient profiles, and that telehealth ERP may not be appropriate for all patients with OCD.

Mental health care providers, including those delivering ERP, should consider when telehealth is and is not appropriate. Importantly, telehealth offers a limited field of view compared to in-person, and providers can only observe what is captured by the camera. In the context of telehealth ERP, patients may engage in subtle avoidant behaviors that are more difficult to observe, which may prevent them from experiencing necessary anxiety during exposure practice. Many providers may have firsthand experience with this, or patients who appear distracted over telehealth mediums because of environmental factors that can be controlled for during in-person services.

As telehealth treatment options appear increasingly likely to stay, ERP providers and intervention researchers should continue identifying patient characteristics that are more and less appropriate for telehealth settings in order to maximize treatment outcomes. Providers should share concerns with patients when delivering telehealth ERP and work to address interfering factors impacting the course of treatment. In circumstances where this is not possible, such as when the patients age or symptom severity prevents effective telehealth ERP, or when treatment progress stalls, providers should speak with patients to determine if it would be beneficial to transition to in-person services.

Both in-person and telehealth ERP are fundamentally the same, however it does appear that subtle differences across these modalities may have differential impacts on treatment outcomes for certain OCD patient presentations. Telehealth ERP, and more broadly telehealth psychotherapy, offers many benefits for patients and providers, however appropriate caution should be exhibited, and providers should use clinical judgment when offering telehealth services.

Dr. Wiese is a clinical psychologist in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, Texas. He is primarily focused on conducting research on OCD and related disorders and providing empirically supported treatments to individuals diagnosed with these conditions.

References

1. Fernandez E et al. Live psychotherapy by video versus in‐person: A meta‐analysis of efficacy and its relationship to types and targets of treatment. Clin Psychol Psychother. 2021 Nov;28(6):1535-49. doi: 10.1002/cpp.2594.

2. Storch EA et al. Preliminary investigation of web-camera delivered cognitive-behavioral therapy for youth with obsessive-compulsive disorder. Psychiatry Res. 2011 Oct 30;189(3):407-12. doi: 10.1016/j.psychres.2011.05.047.

3. Fletcher TL et al. A pilot open trial of video telehealth-delivered exposure and response prevention for obsessive-compulsive disorder in rural Veterans. Mil Psychol. 2021 Oct 28;34(1):83-90. doi: 10.1080/08995605.2021.1970983.

4. Wootton BM. Remote cognitive–behavior therapy for obsessive–compulsive symptoms: a meta-analysis. Clin Psychol Rev. 2016 Feb;43:103-13. doi: 10.1016/j.cpr.2015.10.001.

5. Wiese AD et al. Provider perceptions of telehealth and in-person exposure and response prevention for obsessive–compulsive disorder. Psychiatry Res. 2022 Jul;313:114610. doi: 10.1016/j.psychres.2022.114610.

It is no secret that the COVID-19 pandemic resulted in widespread disruptions in health care services. While providers and resources were limited and many patients were apprehensive to present to health care settings out of concern of disease contraction, telehealth services did offer some relief.

Compared to other specialty care services, mental health care providers were well equipped to handle the expansion of telehealth services, as extensive treatment literature provides strong support for the use of psychotherapeutic interventions over telehealth mediums.¹ This holds true in the context of obsessive-compulsive disorder (OCD), where an impressive literature supports the use of telehealth delivery for the gold-standard psychotherapeutic, exposure and response prevention (ERP).^2,3,4

Through ERP, patients work with a clinician to systematically expose themselves to anxiety-providing triggers while actively resisting compulsive behaviors to learn the distress does go away with time and/or the distress is within their ability to cope. This intervention is conceptually similar to repeatedly watching a scary film, by which continued exposure results in less pronounced emotional reaction with subsequent viewings.

Fortunately for patients and providers, the expansion of telehealth ERP across different treatment settings has had many unintended benefits, including increased access to care, lower no-show rates due to the ease of attending appointments, and the ability to offer higher levels of care, including intensive outpatient programs, over telehealth mediums. Anecdotally, our clinic has been able to increase patient reach by providing telehealth ERP to those who historically would not have been able to access care due to geography. Even for those living within driving distance to our clinic, the ease of joining a video visit for a 45-minute appointment far outweighs driving into the clinic, in many circumstances. With these benefits, the delivery of ERP over telehealth appears likely to stay, although OCD providers delivering ERP will need to consider when and for whom this medium may not be appropriate.

To this end, we recently conducted a study examining ERP providers perceptions of telehealth and in-person ERP, patient characteristics best suited for telehealth services, and provider ability to identify and address factors that adversely impact the course of treatment (e.g., substance use, limited symptom insight, distractions during ERP, etc.).⁵ Providers reported lower feasibility ratings for telehealth compared to in-person ERP for younger patients (aged under 13 years), and patients with more severe OCD presentations. Providers also reported more difficulty identifying and addressing ERP interfering factors over telehealth relative to in-person. The findings from our research do not necessarily speak to the effectiveness of telehealth ERP, which has repeatedly been documented in treatment literature, but rather our findings highlight that ERP providers endorse reservations about the feasibility of ERP for certain OCD patient profiles, and that telehealth ERP may not be appropriate for all patients with OCD.

Mental health care providers, including those delivering ERP, should consider when telehealth is and is not appropriate. Importantly, telehealth offers a limited field of view compared to in-person, and providers can only observe what is captured by the camera. In the context of telehealth ERP, patients may engage in subtle avoidant behaviors that are more difficult to observe, which may prevent them from experiencing necessary anxiety during exposure practice. Many providers may have firsthand experience with this, or patients who appear distracted over telehealth mediums because of environmental factors that can be controlled for during in-person services.

As telehealth treatment options appear increasingly likely to stay, ERP providers and intervention researchers should continue identifying patient characteristics that are more and less appropriate for telehealth settings in order to maximize treatment outcomes. Providers should share concerns with patients when delivering telehealth ERP and work to address interfering factors impacting the course of treatment. In circumstances where this is not possible, such as when the patients age or symptom severity prevents effective telehealth ERP, or when treatment progress stalls, providers should speak with patients to determine if it would be beneficial to transition to in-person services.

Both in-person and telehealth ERP are fundamentally the same, however it does appear that subtle differences across these modalities may have differential impacts on treatment outcomes for certain OCD patient presentations. Telehealth ERP, and more broadly telehealth psychotherapy, offers many benefits for patients and providers, however appropriate caution should be exhibited, and providers should use clinical judgment when offering telehealth services.

Dr. Wiese is a clinical psychologist in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, Texas. He is primarily focused on conducting research on OCD and related disorders and providing empirically supported treatments to individuals diagnosed with these conditions.

References

1. Fernandez E et al. Live psychotherapy by video versus in‐person: A meta‐analysis of efficacy and its relationship to types and targets of treatment. Clin Psychol Psychother. 2021 Nov;28(6):1535-49. doi: 10.1002/cpp.2594.

2. Storch EA et al. Preliminary investigation of web-camera delivered cognitive-behavioral therapy for youth with obsessive-compulsive disorder. Psychiatry Res. 2011 Oct 30;189(3):407-12. doi: 10.1016/j.psychres.2011.05.047.

3. Fletcher TL et al. A pilot open trial of video telehealth-delivered exposure and response prevention for obsessive-compulsive disorder in rural Veterans. Mil Psychol. 2021 Oct 28;34(1):83-90. doi: 10.1080/08995605.2021.1970983.

4. Wootton BM. Remote cognitive–behavior therapy for obsessive–compulsive symptoms: a meta-analysis. Clin Psychol Rev. 2016 Feb;43:103-13. doi: 10.1016/j.cpr.2015.10.001.

5. Wiese AD et al. Provider perceptions of telehealth and in-person exposure and response prevention for obsessive–compulsive disorder. Psychiatry Res. 2022 Jul;313:114610. doi: 10.1016/j.psychres.2022.114610.

Pediatric obesity is a serious problem, not only in the United States but worldwide. Unfortunately, the ongoing COVID-19 pandemic has worsened the epidemic of childhood obesity. Solutions for treating the millions of children and adolescents with obesity are desperately needed because prevention efforts over the past several decades have not been sufficient in slowing the steady rise in obesity prevalence.

Lifestyle modification, including dietary changes, increases in activity, and behavioral modification, are the cornerstone of any obesity treatment, but they alone are not powerful enough to treat obesity by itself in the vast majority of children and adolescents. This is because obesity is not a lifestyle choice; rather, it is a disease, and a disease that has a tremendous amount of biology driving individuals toward weight gain and the propensity toward weight regain if weight is lost.

Fortunately, the tools to treat the underlying biology driving obesity are becoming safer, more effective, and more widely used every year. The two most effective biology-based treatments for pediatric obesity are antiobesity medications and bariatric surgery. These two treatments, when accompanied by lifestyle modification, have the potential to reduce not only body weight but also treat many other risk factors, such as prediabetes, diabetes, high blood pressure, poor cholesterol, liver disease, and sleep apnea, as well as others.
 

Rise in antiobesity medications

Antiobesity medications are developing at a rapid pace. Seven medications have been approved by the Food and Drug Administration for adults, and three medications (phentermine, orlistat, and liraglutide) are now approved for children and adolescents.

The number of antiobesity medications for use in children and adolescents is expected to expand to five, with semaglutide and phentermine-topiramate (Qsymia) both completing trials in adolescents in 2022. Each of these medications works by treating the biology that drives weight gain, whether it is decreasing impulsivity, reducing hunger and appetite hormone pathways, or improving energy regulation pathways. Weight loss at 1 year for currently FDA-approved medications in adolescents ranges from 3% to 6% on average, depending on the medications. The newer medications already FDA approved in adults that will soon, hopefully, be available in pediatrics result in 10%-16% weight loss on average.

A common parent and patient question regarding antiobesity medications is: “If I start an antiobesity medication, how long will I need to be on it?” The simple answer is: “Probably for the rest of your life.”

This can be a shock to hear, but obesity treatment is very similar to that of hypertension or diabetes. Using high blood pressure as an example: If a patient has high blood pressure (for example, 160/90 mm Hg), they will be prescribed a medication to treat it. Once blood pressure comes down to near-normal levels (for example, 120/80 mm Hg), a dose will be maintained, not removed, because that is the biological mediator keeping the blood pressure low. Removal of the medication would result in blood pressure going back to homeostasis (160/90 mm Hg in our example) in a short period of time).

The same can be said for obesity. For example, if a 16-year-old girl is prescribed liraglutide, a glucagonlike peptide–1 receptor agonist, and loses 10% of her body weight at 1 year, that is great success. Why would we remove the medication that is treating the underlying biology causing successful weight loss?

In short, we would not want to do that. Even if our example patient only maintained that 10% initial weight loss, that would be very successful, just like someone maintaining their low blood pressure. As medications begin to develop at a rapid pace and become more available to pediatric patients, the messaging and conversation around anti-obesity medications must continue to focus on obesity being a biological disease and not a behavior for treatment to be effective and not stigmatized.
 

Bariatric surgery most effective treatment for pediatric obesity

Currently, the most effective treatment for pediatric obesity is bariatric surgery. The two most commonly used surgical procedures today are the sleeve gastrectomy and gastric bypass. Sleeve gastrectomy works by removing 75%-85% of the stomach and creating a new stomach, called a “sleeve.” Gastric bypass works by separating the stomach into two parts and connecting one part of the new stomach into the intestine.

Both surgeries are very effective at treating obesity in adolescents, with an average weight loss of 30%-35%. Surgery is not just a restrictive means of controlling body weight; it also changes key hormones for appetite and satiety that signal the brain. In fact, many of the same biological signals that are changed by surgery are the same signals being targeted by antiobesity medications. Long-term outcome of bariatric surgery in adolescents, provided by Teen-LABS, show it to be safe and maybe even more effective than in adults for treating diabetes and hypertension, with similar weight loss.
 

Does treatment outweigh the potential risks?

Although obesity surgery and antiobesity medications are more successful at treating obesity in children and adolescents than lifestyle medications, they do have some risks. Surgery, depending on the type of surgery, can cause nutritional deficiencies, reduce body mineral density, and is a life-changing medical procedure. Antiobesity medications, depending on the type, can cause nausea and vomiting and increase heart rate – and because they are relatively new, we do not fully understand the long-term impact of continued use past 1 year.

However, an important question to ask is: “Do the risks of obesity surgery and antiobesity medications outweigh the risk of having lifelong obesity?” The answer to me and many of my colleagues is: “Yes!” Although there are risks associated with the two best treatments for pediatric obesity, those risks under proper supervision of a medical professional far outweigh the risks of not properly treating obesity and allowing it to persist and get worse over many years to come. Obesity is a disease deeply rooted in biology, and we must use biology-based treatments to tackle this problem in children and adolescents, who deserve the best care and treatments possible.

Dr. Ryder is assistant professor of pediatrics and associate director of research, Center for Pediatric Obesity Medicine, at the University of Minnesota, Minneapolis. She reported receiving donations for clinical trials from Boehringer Ingelheim. A version of this article first appeared on Medscape.com.

Pediatric obesity is a serious problem, not only in the United States but worldwide. Unfortunately, the ongoing COVID-19 pandemic has worsened the epidemic of childhood obesity. Solutions for treating the millions of children and adolescents with obesity are desperately needed because prevention efforts over the past several decades have not been sufficient in slowing the steady rise in obesity prevalence.

Lifestyle modification, including dietary changes, increases in activity, and behavioral modification, are the cornerstone of any obesity treatment, but they alone are not powerful enough to treat obesity by itself in the vast majority of children and adolescents. This is because obesity is not a lifestyle choice; rather, it is a disease, and a disease that has a tremendous amount of biology driving individuals toward weight gain and the propensity toward weight regain if weight is lost.

Fortunately, the tools to treat the underlying biology driving obesity are becoming safer, more effective, and more widely used every year. The two most effective biology-based treatments for pediatric obesity are antiobesity medications and bariatric surgery. These two treatments, when accompanied by lifestyle modification, have the potential to reduce not only body weight but also treat many other risk factors, such as prediabetes, diabetes, high blood pressure, poor cholesterol, liver disease, and sleep apnea, as well as others.
 

Rise in antiobesity medications

Antiobesity medications are developing at a rapid pace. Seven medications have been approved by the Food and Drug Administration for adults, and three medications (phentermine, orlistat, and liraglutide) are now approved for children and adolescents.

The number of antiobesity medications for use in children and adolescents is expected to expand to five, with semaglutide and phentermine-topiramate (Qsymia) both completing trials in adolescents in 2022. Each of these medications works by treating the biology that drives weight gain, whether it is decreasing impulsivity, reducing hunger and appetite hormone pathways, or improving energy regulation pathways. Weight loss at 1 year for currently FDA-approved medications in adolescents ranges from 3% to 6% on average, depending on the medications. The newer medications already FDA approved in adults that will soon, hopefully, be available in pediatrics result in 10%-16% weight loss on average.

A common parent and patient question regarding antiobesity medications is: “If I start an antiobesity medication, how long will I need to be on it?” The simple answer is: “Probably for the rest of your life.”

This can be a shock to hear, but obesity treatment is very similar to that of hypertension or diabetes. Using high blood pressure as an example: If a patient has high blood pressure (for example, 160/90 mm Hg), they will be prescribed a medication to treat it. Once blood pressure comes down to near-normal levels (for example, 120/80 mm Hg), a dose will be maintained, not removed, because that is the biological mediator keeping the blood pressure low. Removal of the medication would result in blood pressure going back to homeostasis (160/90 mm Hg in our example) in a short period of time).

The same can be said for obesity. For example, if a 16-year-old girl is prescribed liraglutide, a glucagonlike peptide–1 receptor agonist, and loses 10% of her body weight at 1 year, that is great success. Why would we remove the medication that is treating the underlying biology causing successful weight loss?

In short, we would not want to do that. Even if our example patient only maintained that 10% initial weight loss, that would be very successful, just like someone maintaining their low blood pressure. As medications begin to develop at a rapid pace and become more available to pediatric patients, the messaging and conversation around anti-obesity medications must continue to focus on obesity being a biological disease and not a behavior for treatment to be effective and not stigmatized.
 

Bariatric surgery most effective treatment for pediatric obesity

Currently, the most effective treatment for pediatric obesity is bariatric surgery. The two most commonly used surgical procedures today are the sleeve gastrectomy and gastric bypass. Sleeve gastrectomy works by removing 75%-85% of the stomach and creating a new stomach, called a “sleeve.” Gastric bypass works by separating the stomach into two parts and connecting one part of the new stomach into the intestine.

Both surgeries are very effective at treating obesity in adolescents, with an average weight loss of 30%-35%. Surgery is not just a restrictive means of controlling body weight; it also changes key hormones for appetite and satiety that signal the brain. In fact, many of the same biological signals that are changed by surgery are the same signals being targeted by antiobesity medications. Long-term outcome of bariatric surgery in adolescents, provided by Teen-LABS, show it to be safe and maybe even more effective than in adults for treating diabetes and hypertension, with similar weight loss.
 

Does treatment outweigh the potential risks?

Although obesity surgery and antiobesity medications are more successful at treating obesity in children and adolescents than lifestyle medications, they do have some risks. Surgery, depending on the type of surgery, can cause nutritional deficiencies, reduce body mineral density, and is a life-changing medical procedure. Antiobesity medications, depending on the type, can cause nausea and vomiting and increase heart rate – and because they are relatively new, we do not fully understand the long-term impact of continued use past 1 year.

However, an important question to ask is: “Do the risks of obesity surgery and antiobesity medications outweigh the risk of having lifelong obesity?” The answer to me and many of my colleagues is: “Yes!” Although there are risks associated with the two best treatments for pediatric obesity, those risks under proper supervision of a medical professional far outweigh the risks of not properly treating obesity and allowing it to persist and get worse over many years to come. Obesity is a disease deeply rooted in biology, and we must use biology-based treatments to tackle this problem in children and adolescents, who deserve the best care and treatments possible.

Dr. Ryder is assistant professor of pediatrics and associate director of research, Center for Pediatric Obesity Medicine, at the University of Minnesota, Minneapolis. She reported receiving donations for clinical trials from Boehringer Ingelheim. A version of this article first appeared on Medscape.com.

Pediatric obesity is a serious problem, not only in the United States but worldwide. Unfortunately, the ongoing COVID-19 pandemic has worsened the epidemic of childhood obesity. Solutions for treating the millions of children and adolescents with obesity are desperately needed because prevention efforts over the past several decades have not been sufficient in slowing the steady rise in obesity prevalence.

Lifestyle modification, including dietary changes, increases in activity, and behavioral modification, are the cornerstone of any obesity treatment, but they alone are not powerful enough to treat obesity by itself in the vast majority of children and adolescents. This is because obesity is not a lifestyle choice; rather, it is a disease, and a disease that has a tremendous amount of biology driving individuals toward weight gain and the propensity toward weight regain if weight is lost.

Fortunately, the tools to treat the underlying biology driving obesity are becoming safer, more effective, and more widely used every year. The two most effective biology-based treatments for pediatric obesity are antiobesity medications and bariatric surgery. These two treatments, when accompanied by lifestyle modification, have the potential to reduce not only body weight but also treat many other risk factors, such as prediabetes, diabetes, high blood pressure, poor cholesterol, liver disease, and sleep apnea, as well as others.
 

Rise in antiobesity medications

Antiobesity medications are developing at a rapid pace. Seven medications have been approved by the Food and Drug Administration for adults, and three medications (phentermine, orlistat, and liraglutide) are now approved for children and adolescents.

The number of antiobesity medications for use in children and adolescents is expected to expand to five, with semaglutide and phentermine-topiramate (Qsymia) both completing trials in adolescents in 2022. Each of these medications works by treating the biology that drives weight gain, whether it is decreasing impulsivity, reducing hunger and appetite hormone pathways, or improving energy regulation pathways. Weight loss at 1 year for currently FDA-approved medications in adolescents ranges from 3% to 6% on average, depending on the medications. The newer medications already FDA approved in adults that will soon, hopefully, be available in pediatrics result in 10%-16% weight loss on average.

A common parent and patient question regarding antiobesity medications is: “If I start an antiobesity medication, how long will I need to be on it?” The simple answer is: “Probably for the rest of your life.”

This can be a shock to hear, but obesity treatment is very similar to that of hypertension or diabetes. Using high blood pressure as an example: If a patient has high blood pressure (for example, 160/90 mm Hg), they will be prescribed a medication to treat it. Once blood pressure comes down to near-normal levels (for example, 120/80 mm Hg), a dose will be maintained, not removed, because that is the biological mediator keeping the blood pressure low. Removal of the medication would result in blood pressure going back to homeostasis (160/90 mm Hg in our example) in a short period of time).

The same can be said for obesity. For example, if a 16-year-old girl is prescribed liraglutide, a glucagonlike peptide–1 receptor agonist, and loses 10% of her body weight at 1 year, that is great success. Why would we remove the medication that is treating the underlying biology causing successful weight loss?

In short, we would not want to do that. Even if our example patient only maintained that 10% initial weight loss, that would be very successful, just like someone maintaining their low blood pressure. As medications begin to develop at a rapid pace and become more available to pediatric patients, the messaging and conversation around anti-obesity medications must continue to focus on obesity being a biological disease and not a behavior for treatment to be effective and not stigmatized.
 

Bariatric surgery most effective treatment for pediatric obesity

Currently, the most effective treatment for pediatric obesity is bariatric surgery. The two most commonly used surgical procedures today are the sleeve gastrectomy and gastric bypass. Sleeve gastrectomy works by removing 75%-85% of the stomach and creating a new stomach, called a “sleeve.” Gastric bypass works by separating the stomach into two parts and connecting one part of the new stomach into the intestine.

Both surgeries are very effective at treating obesity in adolescents, with an average weight loss of 30%-35%. Surgery is not just a restrictive means of controlling body weight; it also changes key hormones for appetite and satiety that signal the brain. In fact, many of the same biological signals that are changed by surgery are the same signals being targeted by antiobesity medications. Long-term outcome of bariatric surgery in adolescents, provided by Teen-LABS, show it to be safe and maybe even more effective than in adults for treating diabetes and hypertension, with similar weight loss.
 

Does treatment outweigh the potential risks?

Although obesity surgery and antiobesity medications are more successful at treating obesity in children and adolescents than lifestyle medications, they do have some risks. Surgery, depending on the type of surgery, can cause nutritional deficiencies, reduce body mineral density, and is a life-changing medical procedure. Antiobesity medications, depending on the type, can cause nausea and vomiting and increase heart rate – and because they are relatively new, we do not fully understand the long-term impact of continued use past 1 year.

However, an important question to ask is: “Do the risks of obesity surgery and antiobesity medications outweigh the risk of having lifelong obesity?” The answer to me and many of my colleagues is: “Yes!” Although there are risks associated with the two best treatments for pediatric obesity, those risks under proper supervision of a medical professional far outweigh the risks of not properly treating obesity and allowing it to persist and get worse over many years to come. Obesity is a disease deeply rooted in biology, and we must use biology-based treatments to tackle this problem in children and adolescents, who deserve the best care and treatments possible.

Dr. Ryder is assistant professor of pediatrics and associate director of research, Center for Pediatric Obesity Medicine, at the University of Minnesota, Minneapolis. She reported receiving donations for clinical trials from Boehringer Ingelheim. A version of this article first appeared on Medscape.com.

Acetyl hexapeptide-8 (or -3), better known by its brand name, Argireline (Lubrizol; Wickliffe, Ohio), is a synthetic peptide gaining popularity in cosmeceutical products for its antiaging benefits. Argireline was developed by the company Lipotec in 2001. Media, beauty bloggers, and product claims have likened this product to a “Botox [or other neurotoxin] alternative,” or “Botox mimicker.”

Mechanism of action

Understanding how Argireline works requires a brief refresher on the mechanism of action of botulinum neurotoxin (BoNT). BoNT relaxes facial muscles and smooths expression lines by inhibiting acetylcholine release at the neuromuscular junction.¹ More specifically, the various serotypes of BoNT are single-chain polypeptides that target members of the SNARE complex: SNAP-25, syntaxin, and Vamp. The proteins within the SNARE complex are involved in the docking and fusion of presynaptic vesicles to the presynaptic membrane, necessary steps for acetylcholine release into the neuromuscular junction and muscle contraction. By blocking the action of the SNARE complex proteins, BoNT inhibits release of acetylcholine in the neuromuscular junction and prevents muscle contraction.

Argireline is a synthetic peptide with the sequence Ac-EEMQRR-NH2.² It is patterned after the N-terminal domain of SNAP-25, one of the members of the SNARE complex targeted by BoNT, and functions to interfere with the assembly of the SNARE complex. In this manner, Argireline would theoretically inhibit fusion of presynaptic vesicles and release of acetylcholine into the neuromuscular junction, thus impeding muscle movement. For this reason, it has been likened to topical Botox. Unlike Botox and other neurotoxins, Argireline was developed for topical application rather than injection.
 

Preclinical studies

In vitro work done 20 years ago demonstrated that Argireline can prevent assembly of the SNARE complex and inhibit neurotransmitter release with a potency similar to that of BoNT A (Botox).²

In 2013, Wang et al. evaluated the histologic effects of Argireline in aged mouse skin induced by D-galactose. For 6 weeks, Argireline was applied twice daily, and histological changes were assessed using hematoxylin and eosin (H&E) and picrosirius–polarization (PSP) stains. The researchers found elevated levels of type I collagen (P < .01) and reduced type III collagen (P < .05) with the Argireline treatment. These results demonstrated that Argireline could histologically enhance collagen in a manner consistent with skin rejuvenation.³
 

Clinical studies

In 2002, Blanes et al. assessed the antiwrinkle activity of Argireline by measuring skin topography from silicone implants in the lateral periorbital region of an oil/water (O/W) emulsion containing 10% of the acetyl-hexapeptide in 10 healthy women volunteers. The hexapeptide emulsion was applied twice daily in one lateral periorbital area, and the emulsion vehicle alone was applied twice daily on the contralateral side. Over 30 days of treatment, wrinkle depth was found to have decreased by 30%. The investigators also found that Argireline significantly hindered neurotransmitter release in vitro as robustly as BoNT A, though with notably lower efficacy. No toxicity or irritation was associated with this treatment.² However, it should be noted that this small study conducted 2 decades ago evaluated only silicone implants with confocal microscopy to evaluate wrinkle depth. There was no subjective clinical assessment of dynamic facial wrinkles. As such, their study is an insufficient basis for drawing conclusions that Argireline is a BoNT mimic. Botox and other types of BoNT affect dynamic facial wrinkles mostly (i.e., wrinkles created by moving muscles of facial expression). This study primarily considers static wrinkles on periorbital skin. While static wrinkles may result from longstanding dynamic wrinkles, BoNT mainly targets dynamic wrinkles, again not comparing apples to apples.

At the same time that Wang et al. conducted their experiment on the skin of aged mice as noted above, they performed a multicenter clinical trial in 60 human subjects who received a randomized treatment of Argireline or placebo in a ratio of 3:1 to assess its safety and efficacy. For 4 weeks, the test product or placebo was applied to periorbital wrinkles twice daily. The researchers found the total antiwrinkle efficacy in the Argireline group to be 48.9% based on the subjective evaluation, compared with 0% in the placebo group. The objective evaluation indicated that all parameters of roughness were diminished in the Argireline group (P < .01), with no reduction observed in the placebo group (P < .05).⁴ There was a little more to appreciate from this study compared with the one reported by Blanes et al., insofar as subjective evaluations and objective evaluations with silica replicas were done. However, this study was not blinded, so the 48.9% wrinkle reduction in the Argireline group vs. 0% in the control group seems suspicious. Additionally, there was a greater focus on static rather than dynamic wrinkles.

In 2017, Raikou et al. conducted a prospective, randomized controlled study to assess the effects of acetyl hexapeptide-3 (Argireline) and tripeptide-10 citrulline in 24 healthy female volunteers (aged 30-60 years) and determine if there was any synergistic action between the peptides. Subjects were randomized to receive a combination of the peptides, tripeptide-10 citrulline only, acetyl hexapeptide-3 only, or neither peptide for 60 days. The researchers found a significant reduction in transepidermal water loss (TEWL) in the Argireline group, compared with the placebo group.⁵ The result of this study makes me question if the decrease in depth of the wrinkles measured in the former studies is really just a measure of increased skin hydration from the Argireline, rather than a neurotoxic effect of Argireline.
 

Formulation and penetration: Can Argireline get through your skin?

One of the fundamental questions regarding Argireline is whether it can penetrate through the stratum corneum and find its target – the facial muscles – where it is intended to function. Argireline is a charged, hydrophilic, and large–molecular weight peptide, and each of these factors impairs penetration through the stratum corneum. Therefore, studies assessing penetration are particularly important.

In 2015, Kraeling et al. conducted an in vitro evaluation of the skin penetration of acetyl hexapeptide-8 in hairless guinea pig and human cadaver skin. An oil-in-water (O/W) emulsion containing 10% acetyl hexapeptide-8 was applied (2 mg/cm²) and penetration was quantified in skin layers via hydrophilic interaction liquid chromatography with tandem mass spectrometry. Most of the acetyl hexapeptide-8 was found to have been washed from human cadaver, as well as guinea pig, skin. Less than 1% of the peptide penetrated the guinea pig or human skin. Of this small amount that penetrated the skin, most stayed in the stratum corneum of guinea pigs (0.54%) and human cadavers (0.22%). The levels of acetyl hexapeptide-8 declined further with each layer of tape stripping removal. Epidermal levels of the peptide in tested skin were similar at 0.01%, and none of the peptide was found in the dermis.⁶ These results indicate negligible penetration by this highly touted peptide ingredient.

Some studies have shown that altering the formulation of acetyl hexapeptide-8 can enhance penetration. Hoppel et al. demonstrated that formulations of the peptide, especially in a water-oil-water (W/O/W emulsion [as compared with O/W and W/O emulsions] can increase penetration into the stratum corneum in porcine skin.⁷ Notably, this is still very superficial relative to the dermis and muscles. Irrespective of formulation, studies have shown that Argireline barely penetrates the stratum corneum, let alone the dermis. Therefore, I would give pause to attributing any clinical impact or benefit of Argireline to its neurotoxinlike effects measured in vitro.
 

Conclusion

Despite the growing popularity of this ingredient in cosmeceuticals and the praise it gets in media for acting as a topical neurotoxin, there are no rigorous clinical trials or data demonstrating its efficacy in suppressing dynamic facial wrinkles like BoNT does. Most importantly, without penetration into the stratum corneum and deeper layers of the skin, it seems unlikely that Argireline’s clinical benefit derives from a neurotoxiclike mechanism of action. It seems more likely that the Argireline-containing product enhances hydration or imparts some other quality to the skin surface. While there is certainly great appeal for a neurotoxinlike product without injections, I do not believe this ingredient will replace injections of BoNT in the foreseeable future, or at least until scientists can figure out how to enable these products to penetrate into the deeper layers of the skin.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Dr. Goldman has no relevant disclosures. Write to her at [email protected] or message her on Instagram @DrChloeGoldman.

References

1. Reddy BY et al. Exp Dermatol. 2012 Aug;21(8):569-75.

2. Blanes-Mira C et al. Int J Cosmet Sci. 2002 Oct;24(5):303-10.

3. Wang Y et al. J Cosmet Laser Ther. 2013 Aug;15(4):237-41.

4. Wang Y et al. J Cosmet Laser Ther. 2013;14(2):147-53.

5. Raikou V et al. J Cosmet Dermatol. 2017 Jun;16(2):271-8.

6. Kraeling ME et al. Cutan Ocul Toxicol. 2015 Mar;34(1):46-52.

7. Hoppel M et al. Eur J Pharm Sci. 2015 Feb 20;68:27-35.

Acetyl hexapeptide-8 (or -3), better known by its brand name, Argireline (Lubrizol; Wickliffe, Ohio), is a synthetic peptide gaining popularity in cosmeceutical products for its antiaging benefits. Argireline was developed by the company Lipotec in 2001. Media, beauty bloggers, and product claims have likened this product to a “Botox [or other neurotoxin] alternative,” or “Botox mimicker.”

Mechanism of action

Understanding how Argireline works requires a brief refresher on the mechanism of action of botulinum neurotoxin (BoNT). BoNT relaxes facial muscles and smooths expression lines by inhibiting acetylcholine release at the neuromuscular junction.¹ More specifically, the various serotypes of BoNT are single-chain polypeptides that target members of the SNARE complex: SNAP-25, syntaxin, and Vamp. The proteins within the SNARE complex are involved in the docking and fusion of presynaptic vesicles to the presynaptic membrane, necessary steps for acetylcholine release into the neuromuscular junction and muscle contraction. By blocking the action of the SNARE complex proteins, BoNT inhibits release of acetylcholine in the neuromuscular junction and prevents muscle contraction.

Argireline is a synthetic peptide with the sequence Ac-EEMQRR-NH2.² It is patterned after the N-terminal domain of SNAP-25, one of the members of the SNARE complex targeted by BoNT, and functions to interfere with the assembly of the SNARE complex. In this manner, Argireline would theoretically inhibit fusion of presynaptic vesicles and release of acetylcholine into the neuromuscular junction, thus impeding muscle movement. For this reason, it has been likened to topical Botox. Unlike Botox and other neurotoxins, Argireline was developed for topical application rather than injection.
 

Preclinical studies

In vitro work done 20 years ago demonstrated that Argireline can prevent assembly of the SNARE complex and inhibit neurotransmitter release with a potency similar to that of BoNT A (Botox).²

In 2013, Wang et al. evaluated the histologic effects of Argireline in aged mouse skin induced by D-galactose. For 6 weeks, Argireline was applied twice daily, and histological changes were assessed using hematoxylin and eosin (H&E) and picrosirius–polarization (PSP) stains. The researchers found elevated levels of type I collagen (P < .01) and reduced type III collagen (P < .05) with the Argireline treatment. These results demonstrated that Argireline could histologically enhance collagen in a manner consistent with skin rejuvenation.³
 

Clinical studies

In 2002, Blanes et al. assessed the antiwrinkle activity of Argireline by measuring skin topography from silicone implants in the lateral periorbital region of an oil/water (O/W) emulsion containing 10% of the acetyl-hexapeptide in 10 healthy women volunteers. The hexapeptide emulsion was applied twice daily in one lateral periorbital area, and the emulsion vehicle alone was applied twice daily on the contralateral side. Over 30 days of treatment, wrinkle depth was found to have decreased by 30%. The investigators also found that Argireline significantly hindered neurotransmitter release in vitro as robustly as BoNT A, though with notably lower efficacy. No toxicity or irritation was associated with this treatment.² However, it should be noted that this small study conducted 2 decades ago evaluated only silicone implants with confocal microscopy to evaluate wrinkle depth. There was no subjective clinical assessment of dynamic facial wrinkles. As such, their study is an insufficient basis for drawing conclusions that Argireline is a BoNT mimic. Botox and other types of BoNT affect dynamic facial wrinkles mostly (i.e., wrinkles created by moving muscles of facial expression). This study primarily considers static wrinkles on periorbital skin. While static wrinkles may result from longstanding dynamic wrinkles, BoNT mainly targets dynamic wrinkles, again not comparing apples to apples.

At the same time that Wang et al. conducted their experiment on the skin of aged mice as noted above, they performed a multicenter clinical trial in 60 human subjects who received a randomized treatment of Argireline or placebo in a ratio of 3:1 to assess its safety and efficacy. For 4 weeks, the test product or placebo was applied to periorbital wrinkles twice daily. The researchers found the total antiwrinkle efficacy in the Argireline group to be 48.9% based on the subjective evaluation, compared with 0% in the placebo group. The objective evaluation indicated that all parameters of roughness were diminished in the Argireline group (P < .01), with no reduction observed in the placebo group (P < .05).⁴ There was a little more to appreciate from this study compared with the one reported by Blanes et al., insofar as subjective evaluations and objective evaluations with silica replicas were done. However, this study was not blinded, so the 48.9% wrinkle reduction in the Argireline group vs. 0% in the control group seems suspicious. Additionally, there was a greater focus on static rather than dynamic wrinkles.

In 2017, Raikou et al. conducted a prospective, randomized controlled study to assess the effects of acetyl hexapeptide-3 (Argireline) and tripeptide-10 citrulline in 24 healthy female volunteers (aged 30-60 years) and determine if there was any synergistic action between the peptides. Subjects were randomized to receive a combination of the peptides, tripeptide-10 citrulline only, acetyl hexapeptide-3 only, or neither peptide for 60 days. The researchers found a significant reduction in transepidermal water loss (TEWL) in the Argireline group, compared with the placebo group.⁵ The result of this study makes me question if the decrease in depth of the wrinkles measured in the former studies is really just a measure of increased skin hydration from the Argireline, rather than a neurotoxic effect of Argireline.
 

Formulation and penetration: Can Argireline get through your skin?

One of the fundamental questions regarding Argireline is whether it can penetrate through the stratum corneum and find its target – the facial muscles – where it is intended to function. Argireline is a charged, hydrophilic, and large–molecular weight peptide, and each of these factors impairs penetration through the stratum corneum. Therefore, studies assessing penetration are particularly important.

In 2015, Kraeling et al. conducted an in vitro evaluation of the skin penetration of acetyl hexapeptide-8 in hairless guinea pig and human cadaver skin. An oil-in-water (O/W) emulsion containing 10% acetyl hexapeptide-8 was applied (2 mg/cm²) and penetration was quantified in skin layers via hydrophilic interaction liquid chromatography with tandem mass spectrometry. Most of the acetyl hexapeptide-8 was found to have been washed from human cadaver, as well as guinea pig, skin. Less than 1% of the peptide penetrated the guinea pig or human skin. Of this small amount that penetrated the skin, most stayed in the stratum corneum of guinea pigs (0.54%) and human cadavers (0.22%). The levels of acetyl hexapeptide-8 declined further with each layer of tape stripping removal. Epidermal levels of the peptide in tested skin were similar at 0.01%, and none of the peptide was found in the dermis.⁶ These results indicate negligible penetration by this highly touted peptide ingredient.

Some studies have shown that altering the formulation of acetyl hexapeptide-8 can enhance penetration. Hoppel et al. demonstrated that formulations of the peptide, especially in a water-oil-water (W/O/W emulsion [as compared with O/W and W/O emulsions] can increase penetration into the stratum corneum in porcine skin.⁷ Notably, this is still very superficial relative to the dermis and muscles. Irrespective of formulation, studies have shown that Argireline barely penetrates the stratum corneum, let alone the dermis. Therefore, I would give pause to attributing any clinical impact or benefit of Argireline to its neurotoxinlike effects measured in vitro.
 

Conclusion

Despite the growing popularity of this ingredient in cosmeceuticals and the praise it gets in media for acting as a topical neurotoxin, there are no rigorous clinical trials or data demonstrating its efficacy in suppressing dynamic facial wrinkles like BoNT does. Most importantly, without penetration into the stratum corneum and deeper layers of the skin, it seems unlikely that Argireline’s clinical benefit derives from a neurotoxiclike mechanism of action. It seems more likely that the Argireline-containing product enhances hydration or imparts some other quality to the skin surface. While there is certainly great appeal for a neurotoxinlike product without injections, I do not believe this ingredient will replace injections of BoNT in the foreseeable future, or at least until scientists can figure out how to enable these products to penetrate into the deeper layers of the skin.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Dr. Goldman has no relevant disclosures. Write to her at [email protected] or message her on Instagram @DrChloeGoldman.

References

1. Reddy BY et al. Exp Dermatol. 2012 Aug;21(8):569-75.

2. Blanes-Mira C et al. Int J Cosmet Sci. 2002 Oct;24(5):303-10.

3. Wang Y et al. J Cosmet Laser Ther. 2013 Aug;15(4):237-41.

4. Wang Y et al. J Cosmet Laser Ther. 2013;14(2):147-53.

5. Raikou V et al. J Cosmet Dermatol. 2017 Jun;16(2):271-8.

6. Kraeling ME et al. Cutan Ocul Toxicol. 2015 Mar;34(1):46-52.

7. Hoppel M et al. Eur J Pharm Sci. 2015 Feb 20;68:27-35.

Acetyl hexapeptide-8 (or -3), better known by its brand name, Argireline (Lubrizol; Wickliffe, Ohio), is a synthetic peptide gaining popularity in cosmeceutical products for its antiaging benefits. Argireline was developed by the company Lipotec in 2001. Media, beauty bloggers, and product claims have likened this product to a “Botox [or other neurotoxin] alternative,” or “Botox mimicker.”

Mechanism of action

Understanding how Argireline works requires a brief refresher on the mechanism of action of botulinum neurotoxin (BoNT). BoNT relaxes facial muscles and smooths expression lines by inhibiting acetylcholine release at the neuromuscular junction.¹ More specifically, the various serotypes of BoNT are single-chain polypeptides that target members of the SNARE complex: SNAP-25, syntaxin, and Vamp. The proteins within the SNARE complex are involved in the docking and fusion of presynaptic vesicles to the presynaptic membrane, necessary steps for acetylcholine release into the neuromuscular junction and muscle contraction. By blocking the action of the SNARE complex proteins, BoNT inhibits release of acetylcholine in the neuromuscular junction and prevents muscle contraction.

Argireline is a synthetic peptide with the sequence Ac-EEMQRR-NH2.² It is patterned after the N-terminal domain of SNAP-25, one of the members of the SNARE complex targeted by BoNT, and functions to interfere with the assembly of the SNARE complex. In this manner, Argireline would theoretically inhibit fusion of presynaptic vesicles and release of acetylcholine into the neuromuscular junction, thus impeding muscle movement. For this reason, it has been likened to topical Botox. Unlike Botox and other neurotoxins, Argireline was developed for topical application rather than injection.
 

Preclinical studies

In vitro work done 20 years ago demonstrated that Argireline can prevent assembly of the SNARE complex and inhibit neurotransmitter release with a potency similar to that of BoNT A (Botox).²

In 2013, Wang et al. evaluated the histologic effects of Argireline in aged mouse skin induced by D-galactose. For 6 weeks, Argireline was applied twice daily, and histological changes were assessed using hematoxylin and eosin (H&E) and picrosirius–polarization (PSP) stains. The researchers found elevated levels of type I collagen (P < .01) and reduced type III collagen (P < .05) with the Argireline treatment. These results demonstrated that Argireline could histologically enhance collagen in a manner consistent with skin rejuvenation.³
 

Clinical studies

In 2002, Blanes et al. assessed the antiwrinkle activity of Argireline by measuring skin topography from silicone implants in the lateral periorbital region of an oil/water (O/W) emulsion containing 10% of the acetyl-hexapeptide in 10 healthy women volunteers. The hexapeptide emulsion was applied twice daily in one lateral periorbital area, and the emulsion vehicle alone was applied twice daily on the contralateral side. Over 30 days of treatment, wrinkle depth was found to have decreased by 30%. The investigators also found that Argireline significantly hindered neurotransmitter release in vitro as robustly as BoNT A, though with notably lower efficacy. No toxicity or irritation was associated with this treatment.² However, it should be noted that this small study conducted 2 decades ago evaluated only silicone implants with confocal microscopy to evaluate wrinkle depth. There was no subjective clinical assessment of dynamic facial wrinkles. As such, their study is an insufficient basis for drawing conclusions that Argireline is a BoNT mimic. Botox and other types of BoNT affect dynamic facial wrinkles mostly (i.e., wrinkles created by moving muscles of facial expression). This study primarily considers static wrinkles on periorbital skin. While static wrinkles may result from longstanding dynamic wrinkles, BoNT mainly targets dynamic wrinkles, again not comparing apples to apples.

At the same time that Wang et al. conducted their experiment on the skin of aged mice as noted above, they performed a multicenter clinical trial in 60 human subjects who received a randomized treatment of Argireline or placebo in a ratio of 3:1 to assess its safety and efficacy. For 4 weeks, the test product or placebo was applied to periorbital wrinkles twice daily. The researchers found the total antiwrinkle efficacy in the Argireline group to be 48.9% based on the subjective evaluation, compared with 0% in the placebo group. The objective evaluation indicated that all parameters of roughness were diminished in the Argireline group (P < .01), with no reduction observed in the placebo group (P < .05).⁴ There was a little more to appreciate from this study compared with the one reported by Blanes et al., insofar as subjective evaluations and objective evaluations with silica replicas were done. However, this study was not blinded, so the 48.9% wrinkle reduction in the Argireline group vs. 0% in the control group seems suspicious. Additionally, there was a greater focus on static rather than dynamic wrinkles.

In 2017, Raikou et al. conducted a prospective, randomized controlled study to assess the effects of acetyl hexapeptide-3 (Argireline) and tripeptide-10 citrulline in 24 healthy female volunteers (aged 30-60 years) and determine if there was any synergistic action between the peptides. Subjects were randomized to receive a combination of the peptides, tripeptide-10 citrulline only, acetyl hexapeptide-3 only, or neither peptide for 60 days. The researchers found a significant reduction in transepidermal water loss (TEWL) in the Argireline group, compared with the placebo group.⁵ The result of this study makes me question if the decrease in depth of the wrinkles measured in the former studies is really just a measure of increased skin hydration from the Argireline, rather than a neurotoxic effect of Argireline.
 

Formulation and penetration: Can Argireline get through your skin?

One of the fundamental questions regarding Argireline is whether it can penetrate through the stratum corneum and find its target – the facial muscles – where it is intended to function. Argireline is a charged, hydrophilic, and large–molecular weight peptide, and each of these factors impairs penetration through the stratum corneum. Therefore, studies assessing penetration are particularly important.

In 2015, Kraeling et al. conducted an in vitro evaluation of the skin penetration of acetyl hexapeptide-8 in hairless guinea pig and human cadaver skin. An oil-in-water (O/W) emulsion containing 10% acetyl hexapeptide-8 was applied (2 mg/cm²) and penetration was quantified in skin layers via hydrophilic interaction liquid chromatography with tandem mass spectrometry. Most of the acetyl hexapeptide-8 was found to have been washed from human cadaver, as well as guinea pig, skin. Less than 1% of the peptide penetrated the guinea pig or human skin. Of this small amount that penetrated the skin, most stayed in the stratum corneum of guinea pigs (0.54%) and human cadavers (0.22%). The levels of acetyl hexapeptide-8 declined further with each layer of tape stripping removal. Epidermal levels of the peptide in tested skin were similar at 0.01%, and none of the peptide was found in the dermis.⁶ These results indicate negligible penetration by this highly touted peptide ingredient.

Some studies have shown that altering the formulation of acetyl hexapeptide-8 can enhance penetration. Hoppel et al. demonstrated that formulations of the peptide, especially in a water-oil-water (W/O/W emulsion [as compared with O/W and W/O emulsions] can increase penetration into the stratum corneum in porcine skin.⁷ Notably, this is still very superficial relative to the dermis and muscles. Irrespective of formulation, studies have shown that Argireline barely penetrates the stratum corneum, let alone the dermis. Therefore, I would give pause to attributing any clinical impact or benefit of Argireline to its neurotoxinlike effects measured in vitro.
 

Conclusion

Despite the growing popularity of this ingredient in cosmeceuticals and the praise it gets in media for acting as a topical neurotoxin, there are no rigorous clinical trials or data demonstrating its efficacy in suppressing dynamic facial wrinkles like BoNT does. Most importantly, without penetration into the stratum corneum and deeper layers of the skin, it seems unlikely that Argireline’s clinical benefit derives from a neurotoxiclike mechanism of action. It seems more likely that the Argireline-containing product enhances hydration or imparts some other quality to the skin surface. While there is certainly great appeal for a neurotoxinlike product without injections, I do not believe this ingredient will replace injections of BoNT in the foreseeable future, or at least until scientists can figure out how to enable these products to penetrate into the deeper layers of the skin.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Dr. Goldman has no relevant disclosures. Write to her at [email protected] or message her on Instagram @DrChloeGoldman.

References

1. Reddy BY et al. Exp Dermatol. 2012 Aug;21(8):569-75.

2. Blanes-Mira C et al. Int J Cosmet Sci. 2002 Oct;24(5):303-10.

3. Wang Y et al. J Cosmet Laser Ther. 2013 Aug;15(4):237-41.

4. Wang Y et al. J Cosmet Laser Ther. 2013;14(2):147-53.

5. Raikou V et al. J Cosmet Dermatol. 2017 Jun;16(2):271-8.

6. Kraeling ME et al. Cutan Ocul Toxicol. 2015 Mar;34(1):46-52.

7. Hoppel M et al. Eur J Pharm Sci. 2015 Feb 20;68:27-35.

The number of overdose deaths involving methadone decreased after the implementation of an early-pandemic policy that allowed some patients with opioid use disorder (OUD) to take methadone at home, new research shows.

Overdose deaths both with and without methadone rose sharply in March 2020, when the policy was announced. Of note, methadone-related deaths decreased in the following months, whereas deaths not involving methadone continued to increase.

“Coupled with research demonstrating improved patient satisfaction, treatment access, and engagement from these policies, these findings can inform decisions about permanently expanding take-home methadone,” the investigators wrote.

The study was published online in JAMA Psychiatry.
 

An essential tool

Before the pandemic, patients seeking methadone treatment for OUD in the United States had to visit a federally certified opioid treatment clinic every day to receive the medication.

In response to the pandemic, the Substance Abuse and Mental Health Services Administration instituted a new policy that allowed states to request exceptions to provide take-home methadone for up to 4 weeks for stable patients and up to 2 weeks for those who were less stable.

To determine the effect of this policy change on overdose death rates, researchers analyzed data on overdose deaths from January 2019 to August 2021.

Overall, the percentage of deaths involving methadone decreased from 4.5% in 2019 to 3.2% in 2021.

The investigators found a sharp increase in all overdose deaths in March 2020. Deaths that did not involve methadone increased by an average of 78.12 more each month before March 2020, increased by an average of 1,078.27 during March 2020, and then continued to increase by an average of 69.07 more each month after March 2020.

Overdose deaths involving methadone increased by a similar amount in March 2020, stabilized, and then decreased 0.05% per month.

Researchers attributed the increase in methadone-related deaths in March 2020 with the rise in overall drug overdose deaths driven by illicitly made fentanyl in the early months of the COVID-19 pandemic.

A study published in JAMA Network Open in March 2022 showed that methadone and other medications to treat OUD are widely underutilized.

That research cited concern over misuse as a key reason for clinicians’ reluctance to prescribe the drugs. The researchers of the current study hope that these new findings lay some of these fears to rest.

“Treatment is an essential tool to stop the addiction and overdose crises, but it is vastly underused,” Nora Volkow, MD, coinvestigator, and director of the National Institute on Drug Abuse, said in a press release. “This evidence adds significant weight to the argument that effective treatment for substance use disorders should be offered in an accessible and practical way that works for people who need it.”

The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. The authors reported no relevant disclosures related to the study.

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

The number of overdose deaths involving methadone decreased after the implementation of an early-pandemic policy that allowed some patients with opioid use disorder (OUD) to take methadone at home, new research shows.

Overdose deaths both with and without methadone rose sharply in March 2020, when the policy was announced. Of note, methadone-related deaths decreased in the following months, whereas deaths not involving methadone continued to increase.

“Coupled with research demonstrating improved patient satisfaction, treatment access, and engagement from these policies, these findings can inform decisions about permanently expanding take-home methadone,” the investigators wrote.

The study was published online in JAMA Psychiatry.
 

An essential tool

Before the pandemic, patients seeking methadone treatment for OUD in the United States had to visit a federally certified opioid treatment clinic every day to receive the medication.

In response to the pandemic, the Substance Abuse and Mental Health Services Administration instituted a new policy that allowed states to request exceptions to provide take-home methadone for up to 4 weeks for stable patients and up to 2 weeks for those who were less stable.

To determine the effect of this policy change on overdose death rates, researchers analyzed data on overdose deaths from January 2019 to August 2021.

Overall, the percentage of deaths involving methadone decreased from 4.5% in 2019 to 3.2% in 2021.

The investigators found a sharp increase in all overdose deaths in March 2020. Deaths that did not involve methadone increased by an average of 78.12 more each month before March 2020, increased by an average of 1,078.27 during March 2020, and then continued to increase by an average of 69.07 more each month after March 2020.

Overdose deaths involving methadone increased by a similar amount in March 2020, stabilized, and then decreased 0.05% per month.

Researchers attributed the increase in methadone-related deaths in March 2020 with the rise in overall drug overdose deaths driven by illicitly made fentanyl in the early months of the COVID-19 pandemic.

A study published in JAMA Network Open in March 2022 showed that methadone and other medications to treat OUD are widely underutilized.

That research cited concern over misuse as a key reason for clinicians’ reluctance to prescribe the drugs. The researchers of the current study hope that these new findings lay some of these fears to rest.

“Treatment is an essential tool to stop the addiction and overdose crises, but it is vastly underused,” Nora Volkow, MD, coinvestigator, and director of the National Institute on Drug Abuse, said in a press release. “This evidence adds significant weight to the argument that effective treatment for substance use disorders should be offered in an accessible and practical way that works for people who need it.”

The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. The authors reported no relevant disclosures related to the study.

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

The number of overdose deaths involving methadone decreased after the implementation of an early-pandemic policy that allowed some patients with opioid use disorder (OUD) to take methadone at home, new research shows.

Overdose deaths both with and without methadone rose sharply in March 2020, when the policy was announced. Of note, methadone-related deaths decreased in the following months, whereas deaths not involving methadone continued to increase.

“Coupled with research demonstrating improved patient satisfaction, treatment access, and engagement from these policies, these findings can inform decisions about permanently expanding take-home methadone,” the investigators wrote.

The study was published online in JAMA Psychiatry.
 

An essential tool

Before the pandemic, patients seeking methadone treatment for OUD in the United States had to visit a federally certified opioid treatment clinic every day to receive the medication.

In response to the pandemic, the Substance Abuse and Mental Health Services Administration instituted a new policy that allowed states to request exceptions to provide take-home methadone for up to 4 weeks for stable patients and up to 2 weeks for those who were less stable.

To determine the effect of this policy change on overdose death rates, researchers analyzed data on overdose deaths from January 2019 to August 2021.

Overall, the percentage of deaths involving methadone decreased from 4.5% in 2019 to 3.2% in 2021.

The investigators found a sharp increase in all overdose deaths in March 2020. Deaths that did not involve methadone increased by an average of 78.12 more each month before March 2020, increased by an average of 1,078.27 during March 2020, and then continued to increase by an average of 69.07 more each month after March 2020.

Overdose deaths involving methadone increased by a similar amount in March 2020, stabilized, and then decreased 0.05% per month.

Researchers attributed the increase in methadone-related deaths in March 2020 with the rise in overall drug overdose deaths driven by illicitly made fentanyl in the early months of the COVID-19 pandemic.

A study published in JAMA Network Open in March 2022 showed that methadone and other medications to treat OUD are widely underutilized.

That research cited concern over misuse as a key reason for clinicians’ reluctance to prescribe the drugs. The researchers of the current study hope that these new findings lay some of these fears to rest.

“Treatment is an essential tool to stop the addiction and overdose crises, but it is vastly underused,” Nora Volkow, MD, coinvestigator, and director of the National Institute on Drug Abuse, said in a press release. “This evidence adds significant weight to the argument that effective treatment for substance use disorders should be offered in an accessible and practical way that works for people who need it.”

The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. The authors reported no relevant disclosures related to the study.

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

The shell game is probably the world’s oldest confidence game, going back 2,000-3,000 years. You still see people getting lured into it in cities today.

It’s also played, albeit legally, in physician offices and pharmacies around the country.

The medical equivalent of the shell game involves one of those ubiquitous manufacturer copay coupons. You know, the ones piled up in your sample cabinet. Get a month free of Whateveritscalled to try and/or have your copay reduced to $0 or something reasonably low. All, of course, subject to terms and conditions in the small print and that of your insurance carrier. Your mileage may vary.

In my experience these things often don’t work as well as advertised. Sometimes it’s because the patient doesn’t understand how to use them, other times because their pharmacy doesn’t want to have anything to do with the cards, and still other times because their insurance has some exclusion against them.

But they do sometimes work ... until they don’t. Sometimes, out of the blue, they’ll stop. Maybe there was an insurance change, or the pharmacy policy changed, or the manufacturer’s program changed, or the offer expired. I usually don’t know and rarely find out.

So the shell game begins. The patients call multiple pharmacies, trying to find one that may be able to honor the coupons. Then they call my office and ask me to switch the script. So I do. They they go to the pharmacy. Sometimes they can get the script, sometimes not. If not, they move to another pharmacy and call my office to switch it again. Wash, rinse, repeat.

Other times it’s more complicated. They want a new card for each try, so they show up at my office asking for one (usually they can be downloaded online so some try that. Others do both). Like pebbles under a shell, the prescriptions and cards get switched from pharmacy to pharmacy.

This isn’t exclusive to manufacturers’ copay cards. I see the same phenomenon with GoodRx and similar cost-saving programs. People move scripts around to find the best deal. It may be helping them, but it certainly doesn’t help me and my staff as we try to keep up, or the badly overworked pharmacy staff.

I’ve even had some patients take the audacious step of asking me to write a script in the name of their spouses so they can double their supply. Obviously, such requests are refused. I’m not going to play that game.

I understand new drugs are costly, and often outside the reach of many patients today. I know the manufacturers are trying to get their products tried, or even make them more affordable for those who need it.

But, in many cases, this becomes (unintentionally or intentionally; I’m not sure) a shell game. Legal, perhaps, but still equally frustrating for all of us who are trying to keep up with it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The shell game is probably the world’s oldest confidence game, going back 2,000-3,000 years. You still see people getting lured into it in cities today.

It’s also played, albeit legally, in physician offices and pharmacies around the country.

The medical equivalent of the shell game involves one of those ubiquitous manufacturer copay coupons. You know, the ones piled up in your sample cabinet. Get a month free of Whateveritscalled to try and/or have your copay reduced to $0 or something reasonably low. All, of course, subject to terms and conditions in the small print and that of your insurance carrier. Your mileage may vary.

In my experience these things often don’t work as well as advertised. Sometimes it’s because the patient doesn’t understand how to use them, other times because their pharmacy doesn’t want to have anything to do with the cards, and still other times because their insurance has some exclusion against them.

But they do sometimes work ... until they don’t. Sometimes, out of the blue, they’ll stop. Maybe there was an insurance change, or the pharmacy policy changed, or the manufacturer’s program changed, or the offer expired. I usually don’t know and rarely find out.

So the shell game begins. The patients call multiple pharmacies, trying to find one that may be able to honor the coupons. Then they call my office and ask me to switch the script. So I do. They they go to the pharmacy. Sometimes they can get the script, sometimes not. If not, they move to another pharmacy and call my office to switch it again. Wash, rinse, repeat.

Other times it’s more complicated. They want a new card for each try, so they show up at my office asking for one (usually they can be downloaded online so some try that. Others do both). Like pebbles under a shell, the prescriptions and cards get switched from pharmacy to pharmacy.

This isn’t exclusive to manufacturers’ copay cards. I see the same phenomenon with GoodRx and similar cost-saving programs. People move scripts around to find the best deal. It may be helping them, but it certainly doesn’t help me and my staff as we try to keep up, or the badly overworked pharmacy staff.

I’ve even had some patients take the audacious step of asking me to write a script in the name of their spouses so they can double their supply. Obviously, such requests are refused. I’m not going to play that game.

I understand new drugs are costly, and often outside the reach of many patients today. I know the manufacturers are trying to get their products tried, or even make them more affordable for those who need it.

But, in many cases, this becomes (unintentionally or intentionally; I’m not sure) a shell game. Legal, perhaps, but still equally frustrating for all of us who are trying to keep up with it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The shell game is probably the world’s oldest confidence game, going back 2,000-3,000 years. You still see people getting lured into it in cities today.

It’s also played, albeit legally, in physician offices and pharmacies around the country.

The medical equivalent of the shell game involves one of those ubiquitous manufacturer copay coupons. You know, the ones piled up in your sample cabinet. Get a month free of Whateveritscalled to try and/or have your copay reduced to $0 or something reasonably low. All, of course, subject to terms and conditions in the small print and that of your insurance carrier. Your mileage may vary.

In my experience these things often don’t work as well as advertised. Sometimes it’s because the patient doesn’t understand how to use them, other times because their pharmacy doesn’t want to have anything to do with the cards, and still other times because their insurance has some exclusion against them.

But they do sometimes work ... until they don’t. Sometimes, out of the blue, they’ll stop. Maybe there was an insurance change, or the pharmacy policy changed, or the manufacturer’s program changed, or the offer expired. I usually don’t know and rarely find out.

So the shell game begins. The patients call multiple pharmacies, trying to find one that may be able to honor the coupons. Then they call my office and ask me to switch the script. So I do. They they go to the pharmacy. Sometimes they can get the script, sometimes not. If not, they move to another pharmacy and call my office to switch it again. Wash, rinse, repeat.

Other times it’s more complicated. They want a new card for each try, so they show up at my office asking for one (usually they can be downloaded online so some try that. Others do both). Like pebbles under a shell, the prescriptions and cards get switched from pharmacy to pharmacy.

This isn’t exclusive to manufacturers’ copay cards. I see the same phenomenon with GoodRx and similar cost-saving programs. People move scripts around to find the best deal. It may be helping them, but it certainly doesn’t help me and my staff as we try to keep up, or the badly overworked pharmacy staff.

I’ve even had some patients take the audacious step of asking me to write a script in the name of their spouses so they can double their supply. Obviously, such requests are refused. I’m not going to play that game.

I understand new drugs are costly, and often outside the reach of many patients today. I know the manufacturers are trying to get their products tried, or even make them more affordable for those who need it.

But, in many cases, this becomes (unintentionally or intentionally; I’m not sure) a shell game. Legal, perhaps, but still equally frustrating for all of us who are trying to keep up with it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Children whose mothers have polycystic ovary syndrome (PCOS) have increased rates of hospitalization for various conditions, including asthma, pneumonia, and ear infection, a study of more than 1 million children shows.

The associations were not particularly strong, according to the researchers. But they raise questions about the reasons for the increased risk and whether interventions such as diet, exercise, or medications could lead to healthier outcomes for children whose mothers have PCOS.

“The findings suggest that maternal PCOS may have a negative impact on offspring development, enough to lead to a measurable increase in the risk of childhood hospitalization,” study coauthor Nathalie Auger, MD, associate professor of epidemiology at University of Montreal, and colleagues reported in Human Reproduction.

“They are minor differences, just enough that we can statistically identify them. They’re not something where everyone should be worrying at this point,” Dr. Auger told this news organization.

Still, some of the hospitalizations, such as those related to infection or allergy, could be prevented with earlier ambulatory care, so some degree of greater awareness among parents and clinicians may be warranted, she said.
 

Thirteen years of follow-up

PCOS – a reproductive disorder characterized by irregular periods, increased male hormones, and metabolic complications – affects some 10% of women. People with the condition are at increased risk for obesity, type 2 diabetes, and cardiovascular disease.

Although prior research has shown that maternal PCOS may be associated with higher body mass index and attention deficit disorder in children, data on long-term childhood health outcomes have been limited, Dr. Auger’s group noted.

To examine illness in children exposed to maternal PCOS, the investigators analyzed hospitalization rates for nearly 1.04 million children in Quebec between 2006 and 2020; 7,160 of the children had mothers with PCOS.

In all, 275,354 children were hospitalized during 13 years of follow-up, including 2,314 whose mothers had PCOS.

Children exposed to PCOS were hospitalized at a rate of 68.9 per 1,000 person-years – roughly 50% more often than the rate of 45.3 per 1,000 person-years for children not exposed to maternal PCOS.

In an analysis that adjusted for maternal characteristics, childhood hospitalization for any reason was 1.32 times more likely for children exposed to maternal PCOS.

Hospitalizations linked to infectious diseases – such as for bronchitis, bronchiolitis, pneumonia, nephritis, otitis media, or meningitis – were 1.31 times more likely among children exposed to PCOS. Allergy-related hospitalizations, such as for allergic asthma and anaphylaxis, were 1.47 times more likely, according to the researchers.

Metabolic hospitalizations were 1.59 times more likely. For gastrointestinal hospitalizations, the hazard ratio was 1.72. For central nervous system hospitalizations, it was 1.74.

The associations were stronger in earlier childhood, and results were similar for boys and girls, the investigators reported.

Hospitalizations for cardiovascular disease, musculoskeletal conditions, or malignancy were not increased.
 

‘Surprising’ links

“The findings are surprising in that some of the conditions that they showed increased risk for, like asthma and some infections, are not conditions that we think of as being typically associated with PCOS,” said Andrea E. Dunaif, MD, chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes, and Bone Disease at Mount Sinai Health System, New York, who was not part of the study team.

Earlier studies of offspring of women with PCOS have suggested that children may be at increased risk for insulin resistance and obesity.

Differences in genetics, intrauterine environments, patterns of health care use by women with PCOS, and behavioral factors, such as diet and how children are raised, are variables that could have contributed to the different hospitalization rates among children exposed to maternal PCOS, Dr. Auger said.

“Everything is interconnected,” she said.

The study was supported by a grant from the Canadian Institutes of Health Research. Dr. Auger has received a career award from Fonds de Recherche du Québec-Santé. Dr. Dunaif has consulted for Novo Nordisk and Fractyl Laboratories (now Fractyl Health).

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

Children whose mothers have polycystic ovary syndrome (PCOS) have increased rates of hospitalization for various conditions, including asthma, pneumonia, and ear infection, a study of more than 1 million children shows.

The associations were not particularly strong, according to the researchers. But they raise questions about the reasons for the increased risk and whether interventions such as diet, exercise, or medications could lead to healthier outcomes for children whose mothers have PCOS.

“The findings suggest that maternal PCOS may have a negative impact on offspring development, enough to lead to a measurable increase in the risk of childhood hospitalization,” study coauthor Nathalie Auger, MD, associate professor of epidemiology at University of Montreal, and colleagues reported in Human Reproduction.

“They are minor differences, just enough that we can statistically identify them. They’re not something where everyone should be worrying at this point,” Dr. Auger told this news organization.

Still, some of the hospitalizations, such as those related to infection or allergy, could be prevented with earlier ambulatory care, so some degree of greater awareness among parents and clinicians may be warranted, she said.
 

Thirteen years of follow-up

PCOS – a reproductive disorder characterized by irregular periods, increased male hormones, and metabolic complications – affects some 10% of women. People with the condition are at increased risk for obesity, type 2 diabetes, and cardiovascular disease.

Although prior research has shown that maternal PCOS may be associated with higher body mass index and attention deficit disorder in children, data on long-term childhood health outcomes have been limited, Dr. Auger’s group noted.

To examine illness in children exposed to maternal PCOS, the investigators analyzed hospitalization rates for nearly 1.04 million children in Quebec between 2006 and 2020; 7,160 of the children had mothers with PCOS.

In all, 275,354 children were hospitalized during 13 years of follow-up, including 2,314 whose mothers had PCOS.

Children exposed to PCOS were hospitalized at a rate of 68.9 per 1,000 person-years – roughly 50% more often than the rate of 45.3 per 1,000 person-years for children not exposed to maternal PCOS.

In an analysis that adjusted for maternal characteristics, childhood hospitalization for any reason was 1.32 times more likely for children exposed to maternal PCOS.

Hospitalizations linked to infectious diseases – such as for bronchitis, bronchiolitis, pneumonia, nephritis, otitis media, or meningitis – were 1.31 times more likely among children exposed to PCOS. Allergy-related hospitalizations, such as for allergic asthma and anaphylaxis, were 1.47 times more likely, according to the researchers.

Metabolic hospitalizations were 1.59 times more likely. For gastrointestinal hospitalizations, the hazard ratio was 1.72. For central nervous system hospitalizations, it was 1.74.

The associations were stronger in earlier childhood, and results were similar for boys and girls, the investigators reported.

Hospitalizations for cardiovascular disease, musculoskeletal conditions, or malignancy were not increased.
 

‘Surprising’ links

“The findings are surprising in that some of the conditions that they showed increased risk for, like asthma and some infections, are not conditions that we think of as being typically associated with PCOS,” said Andrea E. Dunaif, MD, chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes, and Bone Disease at Mount Sinai Health System, New York, who was not part of the study team.

Earlier studies of offspring of women with PCOS have suggested that children may be at increased risk for insulin resistance and obesity.

Differences in genetics, intrauterine environments, patterns of health care use by women with PCOS, and behavioral factors, such as diet and how children are raised, are variables that could have contributed to the different hospitalization rates among children exposed to maternal PCOS, Dr. Auger said.

“Everything is interconnected,” she said.

The study was supported by a grant from the Canadian Institutes of Health Research. Dr. Auger has received a career award from Fonds de Recherche du Québec-Santé. Dr. Dunaif has consulted for Novo Nordisk and Fractyl Laboratories (now Fractyl Health).

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

Children whose mothers have polycystic ovary syndrome (PCOS) have increased rates of hospitalization for various conditions, including asthma, pneumonia, and ear infection, a study of more than 1 million children shows.

The associations were not particularly strong, according to the researchers. But they raise questions about the reasons for the increased risk and whether interventions such as diet, exercise, or medications could lead to healthier outcomes for children whose mothers have PCOS.

“The findings suggest that maternal PCOS may have a negative impact on offspring development, enough to lead to a measurable increase in the risk of childhood hospitalization,” study coauthor Nathalie Auger, MD, associate professor of epidemiology at University of Montreal, and colleagues reported in Human Reproduction.

“They are minor differences, just enough that we can statistically identify them. They’re not something where everyone should be worrying at this point,” Dr. Auger told this news organization.

Still, some of the hospitalizations, such as those related to infection or allergy, could be prevented with earlier ambulatory care, so some degree of greater awareness among parents and clinicians may be warranted, she said.
 

Thirteen years of follow-up

PCOS – a reproductive disorder characterized by irregular periods, increased male hormones, and metabolic complications – affects some 10% of women. People with the condition are at increased risk for obesity, type 2 diabetes, and cardiovascular disease.

Although prior research has shown that maternal PCOS may be associated with higher body mass index and attention deficit disorder in children, data on long-term childhood health outcomes have been limited, Dr. Auger’s group noted.

To examine illness in children exposed to maternal PCOS, the investigators analyzed hospitalization rates for nearly 1.04 million children in Quebec between 2006 and 2020; 7,160 of the children had mothers with PCOS.

In all, 275,354 children were hospitalized during 13 years of follow-up, including 2,314 whose mothers had PCOS.

Children exposed to PCOS were hospitalized at a rate of 68.9 per 1,000 person-years – roughly 50% more often than the rate of 45.3 per 1,000 person-years for children not exposed to maternal PCOS.

In an analysis that adjusted for maternal characteristics, childhood hospitalization for any reason was 1.32 times more likely for children exposed to maternal PCOS.

Hospitalizations linked to infectious diseases – such as for bronchitis, bronchiolitis, pneumonia, nephritis, otitis media, or meningitis – were 1.31 times more likely among children exposed to PCOS. Allergy-related hospitalizations, such as for allergic asthma and anaphylaxis, were 1.47 times more likely, according to the researchers.

Metabolic hospitalizations were 1.59 times more likely. For gastrointestinal hospitalizations, the hazard ratio was 1.72. For central nervous system hospitalizations, it was 1.74.

The associations were stronger in earlier childhood, and results were similar for boys and girls, the investigators reported.

Hospitalizations for cardiovascular disease, musculoskeletal conditions, or malignancy were not increased.
 

‘Surprising’ links

“The findings are surprising in that some of the conditions that they showed increased risk for, like asthma and some infections, are not conditions that we think of as being typically associated with PCOS,” said Andrea E. Dunaif, MD, chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes, and Bone Disease at Mount Sinai Health System, New York, who was not part of the study team.

Earlier studies of offspring of women with PCOS have suggested that children may be at increased risk for insulin resistance and obesity.

Differences in genetics, intrauterine environments, patterns of health care use by women with PCOS, and behavioral factors, such as diet and how children are raised, are variables that could have contributed to the different hospitalization rates among children exposed to maternal PCOS, Dr. Auger said.

“Everything is interconnected,” she said.

The study was supported by a grant from the Canadian Institutes of Health Research. Dr. Auger has received a career award from Fonds de Recherche du Québec-Santé. Dr. Dunaif has consulted for Novo Nordisk and Fractyl Laboratories (now Fractyl Health).

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

Tragic, embarrassing, criminal ... Choose your own adjective. The maternal mortality rate in this country is the worst of any developed nation in the world. And the numbers are getting worse with an increase of 14% over the previous year. One-third of these deaths occur weeks or months after the delivery.

In a recent issue of Harvard Public Health, researchers at the T.H. Chan School of Public Health discuss some of the possible remedies for what they describe as a crisis. While some of the solutions they list will require major restructuring of how we deliver health care to mothers, others could take advantage of our current systems by employing a slight shift in emphasis. And here is where those of us on the frontline of care delivery can make a difference.

The researchers point out that “More than 90% of maternal deaths could be prevented if women had access to quality care.” They also observe that most mothers have a single postpartum check with the ob.gyn. facility that delivered the baby and then are often left to navigate the health system because transfer to their primary care and/or mental health professional is haphazard or lacking in follow-up.

As I read through the article it struck me that as pediatricians we could and should be playing a larger role in this critical postpartum period when so many women seem to be falling through the cracks in our health care nonsystem. This is not a great “Ah-ha” moment for which I deserve any credit. In 2010 the American Academy of Pediatrics recommended that mothers be screened for depression at the 1-, 2-, and 4-month visits using either a validated 10-question screening instrument or a more direct 2-question tool (Pediatrics 2010;126[5]:1032-9). However, a periodic survey of AAP members 3 years later revealed that less than a third of the respondents were screening regularly for postpartum depression. In 2019 the academy reemphasized the important role that pediatric primary care givers can play in the detection and early management of the condition.

The reasons for the disappointing response include the list of usual suspects of inadequate training, workload demands, reimbursement, liability concerns, and the difficulty in finding and establishing effective referral networks. Unfortunately, these factors continue to exist, and many cases have multiplied in the wake of the pandemic.

In some states, educational outreach, funding, and changes in the reimbursement structure have resulted in improved outcomes. Not all of us are fortunate enough to live in a state that has made postpartum depression detection and management a priority. However, simply making it our own professional priority can save lives, ease suffering, and improve postpartum outcomes. Here I am talking about first caring and then inquiring about a mother’s mental health. Asking how much sleep she is getting. And then spending the time to give personalized advice on feeding and sleep schedules. Even, if this means ignoring half of the topics on the recommended health maintenance. It doesn’t take but a few minutes to convince yourself that the baby is healthy, and you know that 90% of them are.

However, a new mother who is sleep deprived and already has one foot on the spiral staircase down into postpartum depression represents an emergency. And, you should have the skills to turn it around. But, you have to care about the problem and make it your own priority – high enough on the list to make a follow-up appointment or call in a week instead of waiting a month or 2 until the next visit.

Unfortunately, even with your best efforts there are some families who need services beyond the scope of your practice. Making the necessary referrals can be frustrating and time consuming but not dropping ball until it lands in the appropriate place may save a life.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Tragic, embarrassing, criminal ... Choose your own adjective. The maternal mortality rate in this country is the worst of any developed nation in the world. And the numbers are getting worse with an increase of 14% over the previous year. One-third of these deaths occur weeks or months after the delivery.

In a recent issue of Harvard Public Health, researchers at the T.H. Chan School of Public Health discuss some of the possible remedies for what they describe as a crisis. While some of the solutions they list will require major restructuring of how we deliver health care to mothers, others could take advantage of our current systems by employing a slight shift in emphasis. And here is where those of us on the frontline of care delivery can make a difference.

The researchers point out that “More than 90% of maternal deaths could be prevented if women had access to quality care.” They also observe that most mothers have a single postpartum check with the ob.gyn. facility that delivered the baby and then are often left to navigate the health system because transfer to their primary care and/or mental health professional is haphazard or lacking in follow-up.

As I read through the article it struck me that as pediatricians we could and should be playing a larger role in this critical postpartum period when so many women seem to be falling through the cracks in our health care nonsystem. This is not a great “Ah-ha” moment for which I deserve any credit. In 2010 the American Academy of Pediatrics recommended that mothers be screened for depression at the 1-, 2-, and 4-month visits using either a validated 10-question screening instrument or a more direct 2-question tool (Pediatrics 2010;126[5]:1032-9). However, a periodic survey of AAP members 3 years later revealed that less than a third of the respondents were screening regularly for postpartum depression. In 2019 the academy reemphasized the important role that pediatric primary care givers can play in the detection and early management of the condition.

The reasons for the disappointing response include the list of usual suspects of inadequate training, workload demands, reimbursement, liability concerns, and the difficulty in finding and establishing effective referral networks. Unfortunately, these factors continue to exist, and many cases have multiplied in the wake of the pandemic.

In some states, educational outreach, funding, and changes in the reimbursement structure have resulted in improved outcomes. Not all of us are fortunate enough to live in a state that has made postpartum depression detection and management a priority. However, simply making it our own professional priority can save lives, ease suffering, and improve postpartum outcomes. Here I am talking about first caring and then inquiring about a mother’s mental health. Asking how much sleep she is getting. And then spending the time to give personalized advice on feeding and sleep schedules. Even, if this means ignoring half of the topics on the recommended health maintenance. It doesn’t take but a few minutes to convince yourself that the baby is healthy, and you know that 90% of them are.

However, a new mother who is sleep deprived and already has one foot on the spiral staircase down into postpartum depression represents an emergency. And, you should have the skills to turn it around. But, you have to care about the problem and make it your own priority – high enough on the list to make a follow-up appointment or call in a week instead of waiting a month or 2 until the next visit.

Unfortunately, even with your best efforts there are some families who need services beyond the scope of your practice. Making the necessary referrals can be frustrating and time consuming but not dropping ball until it lands in the appropriate place may save a life.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Tragic, embarrassing, criminal ... Choose your own adjective. The maternal mortality rate in this country is the worst of any developed nation in the world. And the numbers are getting worse with an increase of 14% over the previous year. One-third of these deaths occur weeks or months after the delivery.

In a recent issue of Harvard Public Health, researchers at the T.H. Chan School of Public Health discuss some of the possible remedies for what they describe as a crisis. While some of the solutions they list will require major restructuring of how we deliver health care to mothers, others could take advantage of our current systems by employing a slight shift in emphasis. And here is where those of us on the frontline of care delivery can make a difference.

The researchers point out that “More than 90% of maternal deaths could be prevented if women had access to quality care.” They also observe that most mothers have a single postpartum check with the ob.gyn. facility that delivered the baby and then are often left to navigate the health system because transfer to their primary care and/or mental health professional is haphazard or lacking in follow-up.

As I read through the article it struck me that as pediatricians we could and should be playing a larger role in this critical postpartum period when so many women seem to be falling through the cracks in our health care nonsystem. This is not a great “Ah-ha” moment for which I deserve any credit. In 2010 the American Academy of Pediatrics recommended that mothers be screened for depression at the 1-, 2-, and 4-month visits using either a validated 10-question screening instrument or a more direct 2-question tool (Pediatrics 2010;126[5]:1032-9). However, a periodic survey of AAP members 3 years later revealed that less than a third of the respondents were screening regularly for postpartum depression. In 2019 the academy reemphasized the important role that pediatric primary care givers can play in the detection and early management of the condition.

The reasons for the disappointing response include the list of usual suspects of inadequate training, workload demands, reimbursement, liability concerns, and the difficulty in finding and establishing effective referral networks. Unfortunately, these factors continue to exist, and many cases have multiplied in the wake of the pandemic.

In some states, educational outreach, funding, and changes in the reimbursement structure have resulted in improved outcomes. Not all of us are fortunate enough to live in a state that has made postpartum depression detection and management a priority. However, simply making it our own professional priority can save lives, ease suffering, and improve postpartum outcomes. Here I am talking about first caring and then inquiring about a mother’s mental health. Asking how much sleep she is getting. And then spending the time to give personalized advice on feeding and sleep schedules. Even, if this means ignoring half of the topics on the recommended health maintenance. It doesn’t take but a few minutes to convince yourself that the baby is healthy, and you know that 90% of them are.

However, a new mother who is sleep deprived and already has one foot on the spiral staircase down into postpartum depression represents an emergency. And, you should have the skills to turn it around. But, you have to care about the problem and make it your own priority – high enough on the list to make a follow-up appointment or call in a week instead of waiting a month or 2 until the next visit.

Unfortunately, even with your best efforts there are some families who need services beyond the scope of your practice. Making the necessary referrals can be frustrating and time consuming but not dropping ball until it lands in the appropriate place may save a life.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.