Federal Practitioner

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”¹ Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.

However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.²

Most abortions are performed during the first trimester and can be managed with medications that are very safe.³ In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.⁴ Inability to access an abortion has widely documented negative health effects for women and their children.^5,6

Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.

We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.⁷ The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.

We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.⁸

Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.

A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.

Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.

Specifically, some resources for training can be found at:

• www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
• https://prochoice.org/providers/continuing-medical-education/
• www.reproductiveaccess.org/medicationabortion/

Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.^{8 We have} managed countless other conditions this way, including most recently during the pandemic.

We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.

We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.

Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.

References

1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.

2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.

3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.

4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.

5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.

6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.

7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.

8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.

“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”¹ Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.

However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.²

Most abortions are performed during the first trimester and can be managed with medications that are very safe.³ In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.⁴ Inability to access an abortion has widely documented negative health effects for women and their children.^5,6

Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.

We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.⁷ The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.

We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.⁸

Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.

A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.

Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.

Specifically, some resources for training can be found at:

• www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
• https://prochoice.org/providers/continuing-medical-education/
• www.reproductiveaccess.org/medicationabortion/

Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.^{8 We have} managed countless other conditions this way, including most recently during the pandemic.

We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.

We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.

Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.

References

1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.

2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.

3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.

4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.

5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.

6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.

7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.

8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.

“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”¹ Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.

However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.²

Most abortions are performed during the first trimester and can be managed with medications that are very safe.³ In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.⁴ Inability to access an abortion has widely documented negative health effects for women and their children.^5,6

Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.

We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.⁷ The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.

We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.⁸

Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.

A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.

Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.

Specifically, some resources for training can be found at:

• www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
• https://prochoice.org/providers/continuing-medical-education/
• www.reproductiveaccess.org/medicationabortion/

Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.^{8 We have} managed countless other conditions this way, including most recently during the pandemic.

We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.

We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.

Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.

References

1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.

2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.

3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.

4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.

5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.

6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.

7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.

8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

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

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

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

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

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

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.