Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

We love psychiatry. We love the idea that someone can come to receive care from a physician to alleviate psychological suffering.

Some people experience such severe anguish that they are unable to relate to others. Some are so despondent that they are unable to make decisions. Some are so distressed that their thoughts become inconsistent with reality. We want all those people, and many more, to have access to effective psychiatric care. However, there are reasonable expectations that one should be able to have that a treatment will help, and that appropriate informed consent is given.

One recent article reminded us of this in a particularly poignant way.

The study in question is a recent publication looking at the universal use of psychotherapy for teenagers.¹ At face value, we would have certainly considered this to be a benevolent and well-meaning intervention. Anyone who has been a teenager or has talked to one, is aware of the emotional instability punctuated by episodes of intense anxiety or irritability. It is age appropriate for a teenager to question and explore their identity. Teenagers are notoriously impulsive with a deep desire for validating interpersonal relationships. One could continue to list the symptoms of borderline personality disorder (BPD) and find a lot of similarity with the condition of transitioning from a child to an adult.

It is thus common sense to consider applying the most established therapy for BPD, dialectical behavioral therapy (DBT), to teenagers. The basics of DBT would seem to be helpful to anyone but appear particularly appropriate to this population. Mindfulness, the practice of paying attention to your present experience, allows one to realize that they are trapped in past or hypothetical future moments. Emotional regulation provides the tools that offer a frame for our feelings and involves recognizing feelings and understanding what they mean. Interpersonal work allows one to recognize and adapt to the feelings of others, while learning how to have a healthy voice with others. Distress tolerance is the exercise of learning to experience and contain our feelings.

The study looked at about 1,000 young adolescents, around 13 years old across high schools in Sydney, Australia: 598 adolescents were allocated to the intervention, and 566 to the control. The intervention consisted of eight weekly sessions of DBT lasting about 50 minutes. The results were “contrary to predictions.” Participants who received DBT “reported significantly increased total difficulties,” and “significant increases in depression and anxiety.” The effects were worse in males yet significant in both genders. The study concludes with “a reminder that present enthusiasm for universal dissemination of short-term DBT-based group skills training within schools, specifically in early adolescence, is ahead of the research evidence.”

We can’t help but wonder why the outcomes of the study were this way; here are some ideas:

• Society has natural ways of developing interpersonal skills, emotional regulation, and the ability to appreciate the present. Interpersonal skills are consistently fostered and tested in schools. Navigating high school parties, the process of organizing them, and getting invited to them requires significant social dexterity. Rejection from romantic interest, alienation from peers, rewards for accomplishment, and acceptance by other peers are some of the daily emotional obstacles that teenagers face. Being constantly taught by older individuals and scolded by parents is its own course in mindfulness. Those are few of the many natural processes of interpersonal growth that formalized therapy may impede.

• The universal discussion of psychological terms and psychiatric symptoms may not only destigmatize mental illness, but also normalize and possibly even promote it. While punishing or stigmatizing a child for having mental illness is obviously unacceptable and cruel, we do wonder if the compulsory psychotherapy may provide negative effects. Psychotherapies, especially manualized ones, were developed to alleviate mental suffering. It seems possible that this format normalizes pathology.

In 1961, Erving Goffman described the concept of sane people appearing insane in an asylum as “mortification.” In 2023, we have much improved, but have we done something to internalize patterns of suffering and alienation rather than dispel them? They are given forms that explain what the feeling of depression is when they may have never considered it. They are given tools to handle distress, when distress may not be present.

• Many human beings live on a fairly tight rope of suppression and the less adaptive repression. Suppression is the defense mechanism by which individuals make an effort to put distressing thoughts out of conscious awareness. After a difficult breakup a teenager may ask some friends to go out and watch a movie, making efforts to put negative feelings out of conscious awareness until there is an opportunity to cope adaptively with those stressors.

Repression is the defense mechanism by which individuals make an effort to prevent distressing thoughts from entering conscious awareness in the first place. After a difficult breakup a teenager acts like nothing happened. While not particularly adaptive, many people live with significant repression and without particular anguish. It is possible that uncovering all of those repressed and suppressed feelings through the exploratory work of therapy may destabilize individuals from their tight rope.

• A less problematic explanation could also be what was previously referred to as therapeutic regression. In psychoanalytic theory, patients are generally thought to have a compromise formation, a psychological strategy used to reconcile conflicting drives. The compromise formation is the way a patient balances their desires against moral expectations and the realities of the external world. In therapy, that compromise formation can be challenged, leading to therapeutic regression.

By uncovering and confronting deeply rooted feelings, a patient may find that their symptoms temporarily intensify. This may not be a problem, but a necessary step to growth in some patients. It is possible that a program longer than 8 weeks would have overcome a temporary worsening in outcome measures.

While it’s easy to highlight the darker moments in psychiatric history, psychiatry has grown into a field which offers well-accepted and uncontroversially promoted forms of treatment. This is evolution, exemplified by the mere consideration of the universal use of psychotherapy for teenagers. But this raises important questions about the potential unintended consequences of normalizing and formalizing therapy. It prompted us to reflect on whether psychiatric treatment is always the best solution and if it might, at times, impede natural processes of growth and coping.

In this context, the study on universal DBT-based group skills training for teenagers challenged our assumptions. The unexpected outcomes suggest that societal and educational systems may naturally foster many of the skills that formalized therapy seeks to provide, and may do so with greater efficacy than that which prescriptive psychiatric treatments have to offer. Moreover, the universal discussion of psychiatric symptoms may not only destigmatize mental illness but also normalize it, potentially leading to unnecessary pathology.

Finally, the study prompted us to consider the fine balance that people find themselves in, questioning whether we should be so certain that our interventions can always provide a better outcome than an individual’s current coping mechanisms. These findings serve as a valuable reminder that our enthusiasm for widespread psychiatric interventions should be tempered by rigorous research and a nuanced understanding of human psychology and development.

This study could be an example of the grandiose stance psychiatry has at times taken of late, suggesting the field has an intervention for all that ails you and can serve as a corrective to society’s maladaptive deviations. Rising rates of mental illness in the community are not interpreted as a failing of the field of psychiatry, but as evidence that we need more psychiatrists. Acts of gun violence, ever increasing rates suicides, and even political disagreements are met with the idea that if only we had more mental health capacity, this could be avoided. This study suggests that not only is psychiatry potentially unhelpful in addressing the vicissitudes of mental anguish, but also may in fact, by its very promotion, be exacerbating them.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest. Dr. ZoBell is a fourth-year senior resident at UCSD Psychiatry Residency Program. She is currently serving as the program’s Chief Resident at the VA San Diego on the inpatient psychiatric unit. Dr. ZoBell is interested in outpatient and emergency psychiatry as well as psychotherapy. Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest.

Reference

1. Harvey, LJ, et al. Investigating the efficacy of a Dialectical behaviour therapy-based universal intervention on adolescent social and emotional well-being outcomes. Behav Res Ther. 2023 Oct. doi: 10.1016/j.brat.2023.104408.

We love psychiatry. We love the idea that someone can come to receive care from a physician to alleviate psychological suffering.

Some people experience such severe anguish that they are unable to relate to others. Some are so despondent that they are unable to make decisions. Some are so distressed that their thoughts become inconsistent with reality. We want all those people, and many more, to have access to effective psychiatric care. However, there are reasonable expectations that one should be able to have that a treatment will help, and that appropriate informed consent is given.

One recent article reminded us of this in a particularly poignant way.

The study in question is a recent publication looking at the universal use of psychotherapy for teenagers.¹ At face value, we would have certainly considered this to be a benevolent and well-meaning intervention. Anyone who has been a teenager or has talked to one, is aware of the emotional instability punctuated by episodes of intense anxiety or irritability. It is age appropriate for a teenager to question and explore their identity. Teenagers are notoriously impulsive with a deep desire for validating interpersonal relationships. One could continue to list the symptoms of borderline personality disorder (BPD) and find a lot of similarity with the condition of transitioning from a child to an adult.

It is thus common sense to consider applying the most established therapy for BPD, dialectical behavioral therapy (DBT), to teenagers. The basics of DBT would seem to be helpful to anyone but appear particularly appropriate to this population. Mindfulness, the practice of paying attention to your present experience, allows one to realize that they are trapped in past or hypothetical future moments. Emotional regulation provides the tools that offer a frame for our feelings and involves recognizing feelings and understanding what they mean. Interpersonal work allows one to recognize and adapt to the feelings of others, while learning how to have a healthy voice with others. Distress tolerance is the exercise of learning to experience and contain our feelings.

The study looked at about 1,000 young adolescents, around 13 years old across high schools in Sydney, Australia: 598 adolescents were allocated to the intervention, and 566 to the control. The intervention consisted of eight weekly sessions of DBT lasting about 50 minutes. The results were “contrary to predictions.” Participants who received DBT “reported significantly increased total difficulties,” and “significant increases in depression and anxiety.” The effects were worse in males yet significant in both genders. The study concludes with “a reminder that present enthusiasm for universal dissemination of short-term DBT-based group skills training within schools, specifically in early adolescence, is ahead of the research evidence.”

We can’t help but wonder why the outcomes of the study were this way; here are some ideas:

• Society has natural ways of developing interpersonal skills, emotional regulation, and the ability to appreciate the present. Interpersonal skills are consistently fostered and tested in schools. Navigating high school parties, the process of organizing them, and getting invited to them requires significant social dexterity. Rejection from romantic interest, alienation from peers, rewards for accomplishment, and acceptance by other peers are some of the daily emotional obstacles that teenagers face. Being constantly taught by older individuals and scolded by parents is its own course in mindfulness. Those are few of the many natural processes of interpersonal growth that formalized therapy may impede.

• The universal discussion of psychological terms and psychiatric symptoms may not only destigmatize mental illness, but also normalize and possibly even promote it. While punishing or stigmatizing a child for having mental illness is obviously unacceptable and cruel, we do wonder if the compulsory psychotherapy may provide negative effects. Psychotherapies, especially manualized ones, were developed to alleviate mental suffering. It seems possible that this format normalizes pathology.

In 1961, Erving Goffman described the concept of sane people appearing insane in an asylum as “mortification.” In 2023, we have much improved, but have we done something to internalize patterns of suffering and alienation rather than dispel them? They are given forms that explain what the feeling of depression is when they may have never considered it. They are given tools to handle distress, when distress may not be present.

• Many human beings live on a fairly tight rope of suppression and the less adaptive repression. Suppression is the defense mechanism by which individuals make an effort to put distressing thoughts out of conscious awareness. After a difficult breakup a teenager may ask some friends to go out and watch a movie, making efforts to put negative feelings out of conscious awareness until there is an opportunity to cope adaptively with those stressors.

Repression is the defense mechanism by which individuals make an effort to prevent distressing thoughts from entering conscious awareness in the first place. After a difficult breakup a teenager acts like nothing happened. While not particularly adaptive, many people live with significant repression and without particular anguish. It is possible that uncovering all of those repressed and suppressed feelings through the exploratory work of therapy may destabilize individuals from their tight rope.

• A less problematic explanation could also be what was previously referred to as therapeutic regression. In psychoanalytic theory, patients are generally thought to have a compromise formation, a psychological strategy used to reconcile conflicting drives. The compromise formation is the way a patient balances their desires against moral expectations and the realities of the external world. In therapy, that compromise formation can be challenged, leading to therapeutic regression.

By uncovering and confronting deeply rooted feelings, a patient may find that their symptoms temporarily intensify. This may not be a problem, but a necessary step to growth in some patients. It is possible that a program longer than 8 weeks would have overcome a temporary worsening in outcome measures.

While it’s easy to highlight the darker moments in psychiatric history, psychiatry has grown into a field which offers well-accepted and uncontroversially promoted forms of treatment. This is evolution, exemplified by the mere consideration of the universal use of psychotherapy for teenagers. But this raises important questions about the potential unintended consequences of normalizing and formalizing therapy. It prompted us to reflect on whether psychiatric treatment is always the best solution and if it might, at times, impede natural processes of growth and coping.

In this context, the study on universal DBT-based group skills training for teenagers challenged our assumptions. The unexpected outcomes suggest that societal and educational systems may naturally foster many of the skills that formalized therapy seeks to provide, and may do so with greater efficacy than that which prescriptive psychiatric treatments have to offer. Moreover, the universal discussion of psychiatric symptoms may not only destigmatize mental illness but also normalize it, potentially leading to unnecessary pathology.

Finally, the study prompted us to consider the fine balance that people find themselves in, questioning whether we should be so certain that our interventions can always provide a better outcome than an individual’s current coping mechanisms. These findings serve as a valuable reminder that our enthusiasm for widespread psychiatric interventions should be tempered by rigorous research and a nuanced understanding of human psychology and development.

This study could be an example of the grandiose stance psychiatry has at times taken of late, suggesting the field has an intervention for all that ails you and can serve as a corrective to society’s maladaptive deviations. Rising rates of mental illness in the community are not interpreted as a failing of the field of psychiatry, but as evidence that we need more psychiatrists. Acts of gun violence, ever increasing rates suicides, and even political disagreements are met with the idea that if only we had more mental health capacity, this could be avoided. This study suggests that not only is psychiatry potentially unhelpful in addressing the vicissitudes of mental anguish, but also may in fact, by its very promotion, be exacerbating them.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest. Dr. ZoBell is a fourth-year senior resident at UCSD Psychiatry Residency Program. She is currently serving as the program’s Chief Resident at the VA San Diego on the inpatient psychiatric unit. Dr. ZoBell is interested in outpatient and emergency psychiatry as well as psychotherapy. Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest.

Reference

1. Harvey, LJ, et al. Investigating the efficacy of a Dialectical behaviour therapy-based universal intervention on adolescent social and emotional well-being outcomes. Behav Res Ther. 2023 Oct. doi: 10.1016/j.brat.2023.104408.

We love psychiatry. We love the idea that someone can come to receive care from a physician to alleviate psychological suffering.

Some people experience such severe anguish that they are unable to relate to others. Some are so despondent that they are unable to make decisions. Some are so distressed that their thoughts become inconsistent with reality. We want all those people, and many more, to have access to effective psychiatric care. However, there are reasonable expectations that one should be able to have that a treatment will help, and that appropriate informed consent is given.

One recent article reminded us of this in a particularly poignant way.

The study in question is a recent publication looking at the universal use of psychotherapy for teenagers.¹ At face value, we would have certainly considered this to be a benevolent and well-meaning intervention. Anyone who has been a teenager or has talked to one, is aware of the emotional instability punctuated by episodes of intense anxiety or irritability. It is age appropriate for a teenager to question and explore their identity. Teenagers are notoriously impulsive with a deep desire for validating interpersonal relationships. One could continue to list the symptoms of borderline personality disorder (BPD) and find a lot of similarity with the condition of transitioning from a child to an adult.

It is thus common sense to consider applying the most established therapy for BPD, dialectical behavioral therapy (DBT), to teenagers. The basics of DBT would seem to be helpful to anyone but appear particularly appropriate to this population. Mindfulness, the practice of paying attention to your present experience, allows one to realize that they are trapped in past or hypothetical future moments. Emotional regulation provides the tools that offer a frame for our feelings and involves recognizing feelings and understanding what they mean. Interpersonal work allows one to recognize and adapt to the feelings of others, while learning how to have a healthy voice with others. Distress tolerance is the exercise of learning to experience and contain our feelings.

The study looked at about 1,000 young adolescents, around 13 years old across high schools in Sydney, Australia: 598 adolescents were allocated to the intervention, and 566 to the control. The intervention consisted of eight weekly sessions of DBT lasting about 50 minutes. The results were “contrary to predictions.” Participants who received DBT “reported significantly increased total difficulties,” and “significant increases in depression and anxiety.” The effects were worse in males yet significant in both genders. The study concludes with “a reminder that present enthusiasm for universal dissemination of short-term DBT-based group skills training within schools, specifically in early adolescence, is ahead of the research evidence.”

We can’t help but wonder why the outcomes of the study were this way; here are some ideas:

• Society has natural ways of developing interpersonal skills, emotional regulation, and the ability to appreciate the present. Interpersonal skills are consistently fostered and tested in schools. Navigating high school parties, the process of organizing them, and getting invited to them requires significant social dexterity. Rejection from romantic interest, alienation from peers, rewards for accomplishment, and acceptance by other peers are some of the daily emotional obstacles that teenagers face. Being constantly taught by older individuals and scolded by parents is its own course in mindfulness. Those are few of the many natural processes of interpersonal growth that formalized therapy may impede.

• The universal discussion of psychological terms and psychiatric symptoms may not only destigmatize mental illness, but also normalize and possibly even promote it. While punishing or stigmatizing a child for having mental illness is obviously unacceptable and cruel, we do wonder if the compulsory psychotherapy may provide negative effects. Psychotherapies, especially manualized ones, were developed to alleviate mental suffering. It seems possible that this format normalizes pathology.

In 1961, Erving Goffman described the concept of sane people appearing insane in an asylum as “mortification.” In 2023, we have much improved, but have we done something to internalize patterns of suffering and alienation rather than dispel them? They are given forms that explain what the feeling of depression is when they may have never considered it. They are given tools to handle distress, when distress may not be present.

• Many human beings live on a fairly tight rope of suppression and the less adaptive repression. Suppression is the defense mechanism by which individuals make an effort to put distressing thoughts out of conscious awareness. After a difficult breakup a teenager may ask some friends to go out and watch a movie, making efforts to put negative feelings out of conscious awareness until there is an opportunity to cope adaptively with those stressors.

Repression is the defense mechanism by which individuals make an effort to prevent distressing thoughts from entering conscious awareness in the first place. After a difficult breakup a teenager acts like nothing happened. While not particularly adaptive, many people live with significant repression and without particular anguish. It is possible that uncovering all of those repressed and suppressed feelings through the exploratory work of therapy may destabilize individuals from their tight rope.

• A less problematic explanation could also be what was previously referred to as therapeutic regression. In psychoanalytic theory, patients are generally thought to have a compromise formation, a psychological strategy used to reconcile conflicting drives. The compromise formation is the way a patient balances their desires against moral expectations and the realities of the external world. In therapy, that compromise formation can be challenged, leading to therapeutic regression.

By uncovering and confronting deeply rooted feelings, a patient may find that their symptoms temporarily intensify. This may not be a problem, but a necessary step to growth in some patients. It is possible that a program longer than 8 weeks would have overcome a temporary worsening in outcome measures.

While it’s easy to highlight the darker moments in psychiatric history, psychiatry has grown into a field which offers well-accepted and uncontroversially promoted forms of treatment. This is evolution, exemplified by the mere consideration of the universal use of psychotherapy for teenagers. But this raises important questions about the potential unintended consequences of normalizing and formalizing therapy. It prompted us to reflect on whether psychiatric treatment is always the best solution and if it might, at times, impede natural processes of growth and coping.

In this context, the study on universal DBT-based group skills training for teenagers challenged our assumptions. The unexpected outcomes suggest that societal and educational systems may naturally foster many of the skills that formalized therapy seeks to provide, and may do so with greater efficacy than that which prescriptive psychiatric treatments have to offer. Moreover, the universal discussion of psychiatric symptoms may not only destigmatize mental illness but also normalize it, potentially leading to unnecessary pathology.

Finally, the study prompted us to consider the fine balance that people find themselves in, questioning whether we should be so certain that our interventions can always provide a better outcome than an individual’s current coping mechanisms. These findings serve as a valuable reminder that our enthusiasm for widespread psychiatric interventions should be tempered by rigorous research and a nuanced understanding of human psychology and development.

This study could be an example of the grandiose stance psychiatry has at times taken of late, suggesting the field has an intervention for all that ails you and can serve as a corrective to society’s maladaptive deviations. Rising rates of mental illness in the community are not interpreted as a failing of the field of psychiatry, but as evidence that we need more psychiatrists. Acts of gun violence, ever increasing rates suicides, and even political disagreements are met with the idea that if only we had more mental health capacity, this could be avoided. This study suggests that not only is psychiatry potentially unhelpful in addressing the vicissitudes of mental anguish, but also may in fact, by its very promotion, be exacerbating them.

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest. Dr. ZoBell is a fourth-year senior resident at UCSD Psychiatry Residency Program. She is currently serving as the program’s Chief Resident at the VA San Diego on the inpatient psychiatric unit. Dr. ZoBell is interested in outpatient and emergency psychiatry as well as psychotherapy. Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest.

Reference

1. Harvey, LJ, et al. Investigating the efficacy of a Dialectical behaviour therapy-based universal intervention on adolescent social and emotional well-being outcomes. Behav Res Ther. 2023 Oct. doi: 10.1016/j.brat.2023.104408.

Hypertrophic lichen planus (HLP), also known as LP verrucosus, is a form of lichen planus where lesions are lichenified and thicker than the typical flat, purple, polygonal lesions found in lichen planus. Lesions may have a covering of scale. HLP commonly affects middle aged men and women. Lesions are most commonly located bilaterally on the shins and ankles and can be painful or pruritic. The differential diagnosis for the condition includes lichen simplex chronicus, connective tissue disease, and other skin disorders that cause hyperkeratosis. This wide differential makes histopathological analysis a useful tool in confirming the diagnosis of HLP.

A definitive diagnosis can be made via skin biopsy. Histopathology reveals hyperkeratosis, acanthosis, and a band-like lymphocytic infiltrate in the dermis. An eosinophilic infiltrate may be present. Other common features include saw tooth rete ridges and Civatte bodies, which are apoptotic keratinocytes. The lymphocytic infiltrate may indicate an autoimmune etiology in which the body’s immune system erroneously attacks itself. However, the exact cause is not known and genetic and environmental factors may play a role.

The treatment of HLP includes symptomatic management and control of inflammation. Topical steroids can be prescribed to manage the inflammation and associated pruritus, and emollient creams and moisturizers are helpful in controlling the dryness. Oral steroids, immunosuppressant medications, or retinoids may be necessary in more severe cases. In addition, psoralen plus ultraviolet A (PUVA) light therapy has been found to be beneficial in some cases. Squamous cell carcinoma may arise in lesions.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Arnold DL, Krishnamurthy K. Lichen Planus. [Updated 2023 Jun 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526126/

Jaime TJ et al. An Bras Dermatol. 2011 Jul-Aug;86(4 Suppl 1):S96-9.

Mirchandani S et al. Med Pharm Rep. 2020 Apr;93(2):210-2. .

Whittington CP et al. Arch Pathol Lab Med. 2023 Jun 19. doi: 10.5858/arpa.2022-0515-RA.

Hypertrophic lichen planus (HLP), also known as LP verrucosus, is a form of lichen planus where lesions are lichenified and thicker than the typical flat, purple, polygonal lesions found in lichen planus. Lesions may have a covering of scale. HLP commonly affects middle aged men and women. Lesions are most commonly located bilaterally on the shins and ankles and can be painful or pruritic. The differential diagnosis for the condition includes lichen simplex chronicus, connective tissue disease, and other skin disorders that cause hyperkeratosis. This wide differential makes histopathological analysis a useful tool in confirming the diagnosis of HLP.

A definitive diagnosis can be made via skin biopsy. Histopathology reveals hyperkeratosis, acanthosis, and a band-like lymphocytic infiltrate in the dermis. An eosinophilic infiltrate may be present. Other common features include saw tooth rete ridges and Civatte bodies, which are apoptotic keratinocytes. The lymphocytic infiltrate may indicate an autoimmune etiology in which the body’s immune system erroneously attacks itself. However, the exact cause is not known and genetic and environmental factors may play a role.

The treatment of HLP includes symptomatic management and control of inflammation. Topical steroids can be prescribed to manage the inflammation and associated pruritus, and emollient creams and moisturizers are helpful in controlling the dryness. Oral steroids, immunosuppressant medications, or retinoids may be necessary in more severe cases. In addition, psoralen plus ultraviolet A (PUVA) light therapy has been found to be beneficial in some cases. Squamous cell carcinoma may arise in lesions.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Arnold DL, Krishnamurthy K. Lichen Planus. [Updated 2023 Jun 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526126/

Jaime TJ et al. An Bras Dermatol. 2011 Jul-Aug;86(4 Suppl 1):S96-9.

Mirchandani S et al. Med Pharm Rep. 2020 Apr;93(2):210-2. .

Whittington CP et al. Arch Pathol Lab Med. 2023 Jun 19. doi: 10.5858/arpa.2022-0515-RA.

Hypertrophic lichen planus (HLP), also known as LP verrucosus, is a form of lichen planus where lesions are lichenified and thicker than the typical flat, purple, polygonal lesions found in lichen planus. Lesions may have a covering of scale. HLP commonly affects middle aged men and women. Lesions are most commonly located bilaterally on the shins and ankles and can be painful or pruritic. The differential diagnosis for the condition includes lichen simplex chronicus, connective tissue disease, and other skin disorders that cause hyperkeratosis. This wide differential makes histopathological analysis a useful tool in confirming the diagnosis of HLP.

A definitive diagnosis can be made via skin biopsy. Histopathology reveals hyperkeratosis, acanthosis, and a band-like lymphocytic infiltrate in the dermis. An eosinophilic infiltrate may be present. Other common features include saw tooth rete ridges and Civatte bodies, which are apoptotic keratinocytes. The lymphocytic infiltrate may indicate an autoimmune etiology in which the body’s immune system erroneously attacks itself. However, the exact cause is not known and genetic and environmental factors may play a role.

The treatment of HLP includes symptomatic management and control of inflammation. Topical steroids can be prescribed to manage the inflammation and associated pruritus, and emollient creams and moisturizers are helpful in controlling the dryness. Oral steroids, immunosuppressant medications, or retinoids may be necessary in more severe cases. In addition, psoralen plus ultraviolet A (PUVA) light therapy has been found to be beneficial in some cases. Squamous cell carcinoma may arise in lesions.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Arnold DL, Krishnamurthy K. Lichen Planus. [Updated 2023 Jun 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526126/

Jaime TJ et al. An Bras Dermatol. 2011 Jul-Aug;86(4 Suppl 1):S96-9.

Mirchandani S et al. Med Pharm Rep. 2020 Apr;93(2):210-2. .

Whittington CP et al. Arch Pathol Lab Med. 2023 Jun 19. doi: 10.5858/arpa.2022-0515-RA.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Dr. Chovatiya

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

Depression, constipation, cystitis/urinary tract infections (UTIs), and sexual dysfunction may be early warning signs of multiple sclerosis (MS) 5 years prior to diagnosis, new research shows.

However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.

“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
 

Retracing MS Origins

The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.

Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.

Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.

After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:

• Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
• Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
• Constipation (OR, 1.5; 95% CI, 1.27-1.78)
• Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
• UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)

However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.

“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.

“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.

A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.

It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
 

Preventing Disease Evolution

In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.

“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.

“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.

The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).

I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.

ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.

How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.

What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.

For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.

To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.

So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.

What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.

I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.

In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.

Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.

What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.

“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.

Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.

But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.

Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.

Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

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

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

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

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

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

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.