When I first became an attending, I was struck by how difficult it was to teach endoscopy effectively. As a fellow, I saw the various teaching styles of my attendings, and it was easy to pick out the best teachers from the group. But when the roles switched, and suddenly I was the supervising faculty member, it was hard to recall exactly what those teachers were doing to create an optimal learning environment in the endoscopy suite. Not only did I lack a framework on how to teach endoscopy, I also was still building confidence in my own endoscopic skills while feeling the pressure to keep my room running on time. All in all, although I loved the opportunity to teach, I found the experience to be quite stressful.

Hoping to find some guidance, I turned to the literature and was fortunate to find some great pieces on how to teach endoscopy effectively. I learned of cognitive load theory – the idea that short-term or “working memory” can manage only a few pieces of information at a time – and how excess feedback or other external distractions (e.g., pagers) during a procedure can overwhelm a learner and lead to declining performance.¹ I also read about the pursuit of “conscious competence,” where an endoscopist can verbalize the steps of a maneuver so that a trainee can remain on the scope and maximize hands-on participation.²

Motivated to bring these key concepts together in an evidence-based framework, I helped lead a Delphi study of GI fellowship program directors and endoscopy education experts to reach consensus on the best practices of teaching endoscopy.³ After two rounds of surveys, the participants identified 10 essential endoscopy teaching practices, which I will summarize in the next sections. What I found most helpful was how these practices were distributed throughout the endoscopy learning experience. By breaking down the complicated task of teaching endoscopy to three discrete parts – prior to the procedure, during the procedure, and after the procedure – I now had a framework to take back to the endoscopy suite.
 

Prior to the procedure

With a busy endoscopy schedule and increasing clinical demands, it is tempting to use the time between cases to complete documentation, address patient messages, and review emails. While this is great for efficiency, make sure to also reserve time to set the stage for your fellow. One of the key practices during this phase is to assess your fellow’s current procedural competency. I start open-ended by asking my fellows how they have been doing with colonoscopy and then ask if they are working on a specific skill. With this information, I have a sense of how much hands-on assistance they will need, what realistic goals to set for them (e.g., navigate out of the sigmoid colon for an early learner vs. efficiently and independently completing the entire case for a later learner), and the areas to focus my observation to provide feedback after the procedure.

During this preparatory time, faculty should also discuss the patient history and indications for the procedure. Reviewing information such as prior sedation requirements and confirming plans for the procedure (e.g., random colon biopsies in a patient with chronic diarrhea and concern for microscopic colitis) helps ensure a proper plan is in place for the patient while also presenting opportunities for learning. Faculty can take this time to review the steps of a more complicated procedure (e.g., PEG placement) and establish ground rules such as when the attending will take the scope from the trainee. Lastly, make sure that the patient understands the role of the fellow and the supervision you will be providing throughout the case.
 

During the procedure

Once the procedure starts, your most important task is to maintain attention throughout the case – if you do, the other best practices generally fall into place. I am most attentive when I am gowned and positioned next to the fellow. From this vantage point, I can see the patient, the fellow’s hands, and the endoscopy screen, which allows me to readily assist if needed while directly observing the fellow’s performance.

If I need to provide feedback in the moment, I often ask the fellows to pause what they are doing and first listen to my feedback. Taking this “timeout” helps manage their cognitive load such that they can actually hear the feedback. As a general rule, however, I try to reserve the bulk of my feedback for when the procedure is complete (see next section). Another way to manage your fellow’s cognitive load is by using standardized endoscopic language throughout the procedure. For example, rather than say “go to the left” during a colonoscopy, try saying “tip left” or “torque counterclockwise” to provide more clear instructions to the fellow. Holding your fellow’s pager during the procedure is a kind gesture that also helps minimize extraneous cognitive load so that the fellow can focus on the procedure.

If your fellows get to a point where they cannot complete the task despite your giving appropriate feedback, or if patient safety concerns arise, then it is time for you to take hands-on control of the scope. In my experience, most fellows welcome the hands-on assistance as they are overloaded by the difficulty of the procedure. Setting this expectation ahead of time, as noted above, makes for a smoother transition. While assuming control of the scope, try to narrate what you are doing differently so that the fellow can still learn while watching. Once you complete the difficult portion of the procedure (e.g., reducing a loop to reach the cecum), return the scope to the fellow to maximize the hands-on participation (if time permits).
 

After the procedure

In the third and final stage of the endoscopy teaching experience, faculty should take the time to confirm the findings of the procedure with the fellow and discuss next steps in management for the patient. Finding these teachable moments helps solidify the cognitive learning for the fellow while also ensuring the patient receives the appropriate postprocedure recommendations. As part of this process, make sure to review the procedure note drafted by the fellow, and if you need to make any substantive edits, review the changes with the fellow so that he or she can learn for future cases.

To wrap up the session, provide feedback to the fellow on performance based on your direct observation. Make sure to name this process aloud – “Let’s do some feedback” – and start by asking how the fellow felt about the performance, both in terms of what went well and what the fellow would like to improve. Then provide your feedback on the performance and be specific, such as, “I really like how you identified a loop and then reduced around the hepatic flexure.” Conclude by having the fellow set a plan for improvement and make sure to ask for feedback on your own teaching performance.

In conclusion, teaching endoscopy is hard – especially as a junior attending. By breaking down the endoscopy teaching experience into its three components, however, and committing to teaching from start to finish, you can provide high-quality endoscopy education to your fellows while ensuring the best care for your patients.

Dr. Kumar is associate medicine clerkship director at Harvard Medical School, and associate physician in the division of gastroenterology at Brigham and Women’s Hospital, both in Boston. He disclosed having no conflicts of interest. He is on Twitter @NavinKumarMD.

References

1. Dilly CK and Sewell JL. 2017 Sep;153(3):632-36.

2. Waschke KA et al. Best Pract Res Clin Gastroenterol. 2016 Jun;30(3):409-19.

3. Kumar NL et al. Clin Gastroenterol Hepatol. 2020 Mar;18(3):574-79.

When I first became an attending, I was struck by how difficult it was to teach endoscopy effectively. As a fellow, I saw the various teaching styles of my attendings, and it was easy to pick out the best teachers from the group. But when the roles switched, and suddenly I was the supervising faculty member, it was hard to recall exactly what those teachers were doing to create an optimal learning environment in the endoscopy suite. Not only did I lack a framework on how to teach endoscopy, I also was still building confidence in my own endoscopic skills while feeling the pressure to keep my room running on time. All in all, although I loved the opportunity to teach, I found the experience to be quite stressful.

Hoping to find some guidance, I turned to the literature and was fortunate to find some great pieces on how to teach endoscopy effectively. I learned of cognitive load theory – the idea that short-term or “working memory” can manage only a few pieces of information at a time – and how excess feedback or other external distractions (e.g., pagers) during a procedure can overwhelm a learner and lead to declining performance.¹ I also read about the pursuit of “conscious competence,” where an endoscopist can verbalize the steps of a maneuver so that a trainee can remain on the scope and maximize hands-on participation.²

Motivated to bring these key concepts together in an evidence-based framework, I helped lead a Delphi study of GI fellowship program directors and endoscopy education experts to reach consensus on the best practices of teaching endoscopy.³ After two rounds of surveys, the participants identified 10 essential endoscopy teaching practices, which I will summarize in the next sections. What I found most helpful was how these practices were distributed throughout the endoscopy learning experience. By breaking down the complicated task of teaching endoscopy to three discrete parts – prior to the procedure, during the procedure, and after the procedure – I now had a framework to take back to the endoscopy suite.
 

Prior to the procedure

With a busy endoscopy schedule and increasing clinical demands, it is tempting to use the time between cases to complete documentation, address patient messages, and review emails. While this is great for efficiency, make sure to also reserve time to set the stage for your fellow. One of the key practices during this phase is to assess your fellow’s current procedural competency. I start open-ended by asking my fellows how they have been doing with colonoscopy and then ask if they are working on a specific skill. With this information, I have a sense of how much hands-on assistance they will need, what realistic goals to set for them (e.g., navigate out of the sigmoid colon for an early learner vs. efficiently and independently completing the entire case for a later learner), and the areas to focus my observation to provide feedback after the procedure.

During this preparatory time, faculty should also discuss the patient history and indications for the procedure. Reviewing information such as prior sedation requirements and confirming plans for the procedure (e.g., random colon biopsies in a patient with chronic diarrhea and concern for microscopic colitis) helps ensure a proper plan is in place for the patient while also presenting opportunities for learning. Faculty can take this time to review the steps of a more complicated procedure (e.g., PEG placement) and establish ground rules such as when the attending will take the scope from the trainee. Lastly, make sure that the patient understands the role of the fellow and the supervision you will be providing throughout the case.
 

During the procedure

Once the procedure starts, your most important task is to maintain attention throughout the case – if you do, the other best practices generally fall into place. I am most attentive when I am gowned and positioned next to the fellow. From this vantage point, I can see the patient, the fellow’s hands, and the endoscopy screen, which allows me to readily assist if needed while directly observing the fellow’s performance.

If I need to provide feedback in the moment, I often ask the fellows to pause what they are doing and first listen to my feedback. Taking this “timeout” helps manage their cognitive load such that they can actually hear the feedback. As a general rule, however, I try to reserve the bulk of my feedback for when the procedure is complete (see next section). Another way to manage your fellow’s cognitive load is by using standardized endoscopic language throughout the procedure. For example, rather than say “go to the left” during a colonoscopy, try saying “tip left” or “torque counterclockwise” to provide more clear instructions to the fellow. Holding your fellow’s pager during the procedure is a kind gesture that also helps minimize extraneous cognitive load so that the fellow can focus on the procedure.

If your fellows get to a point where they cannot complete the task despite your giving appropriate feedback, or if patient safety concerns arise, then it is time for you to take hands-on control of the scope. In my experience, most fellows welcome the hands-on assistance as they are overloaded by the difficulty of the procedure. Setting this expectation ahead of time, as noted above, makes for a smoother transition. While assuming control of the scope, try to narrate what you are doing differently so that the fellow can still learn while watching. Once you complete the difficult portion of the procedure (e.g., reducing a loop to reach the cecum), return the scope to the fellow to maximize the hands-on participation (if time permits).
 

After the procedure

In the third and final stage of the endoscopy teaching experience, faculty should take the time to confirm the findings of the procedure with the fellow and discuss next steps in management for the patient. Finding these teachable moments helps solidify the cognitive learning for the fellow while also ensuring the patient receives the appropriate postprocedure recommendations. As part of this process, make sure to review the procedure note drafted by the fellow, and if you need to make any substantive edits, review the changes with the fellow so that he or she can learn for future cases.

To wrap up the session, provide feedback to the fellow on performance based on your direct observation. Make sure to name this process aloud – “Let’s do some feedback” – and start by asking how the fellow felt about the performance, both in terms of what went well and what the fellow would like to improve. Then provide your feedback on the performance and be specific, such as, “I really like how you identified a loop and then reduced around the hepatic flexure.” Conclude by having the fellow set a plan for improvement and make sure to ask for feedback on your own teaching performance.

In conclusion, teaching endoscopy is hard – especially as a junior attending. By breaking down the endoscopy teaching experience into its three components, however, and committing to teaching from start to finish, you can provide high-quality endoscopy education to your fellows while ensuring the best care for your patients.

Dr. Kumar is associate medicine clerkship director at Harvard Medical School, and associate physician in the division of gastroenterology at Brigham and Women’s Hospital, both in Boston. He disclosed having no conflicts of interest. He is on Twitter @NavinKumarMD.

References

1. Dilly CK and Sewell JL. 2017 Sep;153(3):632-36.

2. Waschke KA et al. Best Pract Res Clin Gastroenterol. 2016 Jun;30(3):409-19.

3. Kumar NL et al. Clin Gastroenterol Hepatol. 2020 Mar;18(3):574-79.

When I first became an attending, I was struck by how difficult it was to teach endoscopy effectively. As a fellow, I saw the various teaching styles of my attendings, and it was easy to pick out the best teachers from the group. But when the roles switched, and suddenly I was the supervising faculty member, it was hard to recall exactly what those teachers were doing to create an optimal learning environment in the endoscopy suite. Not only did I lack a framework on how to teach endoscopy, I also was still building confidence in my own endoscopic skills while feeling the pressure to keep my room running on time. All in all, although I loved the opportunity to teach, I found the experience to be quite stressful.

Hoping to find some guidance, I turned to the literature and was fortunate to find some great pieces on how to teach endoscopy effectively. I learned of cognitive load theory – the idea that short-term or “working memory” can manage only a few pieces of information at a time – and how excess feedback or other external distractions (e.g., pagers) during a procedure can overwhelm a learner and lead to declining performance.¹ I also read about the pursuit of “conscious competence,” where an endoscopist can verbalize the steps of a maneuver so that a trainee can remain on the scope and maximize hands-on participation.²

Motivated to bring these key concepts together in an evidence-based framework, I helped lead a Delphi study of GI fellowship program directors and endoscopy education experts to reach consensus on the best practices of teaching endoscopy.³ After two rounds of surveys, the participants identified 10 essential endoscopy teaching practices, which I will summarize in the next sections. What I found most helpful was how these practices were distributed throughout the endoscopy learning experience. By breaking down the complicated task of teaching endoscopy to three discrete parts – prior to the procedure, during the procedure, and after the procedure – I now had a framework to take back to the endoscopy suite.
 

Prior to the procedure

With a busy endoscopy schedule and increasing clinical demands, it is tempting to use the time between cases to complete documentation, address patient messages, and review emails. While this is great for efficiency, make sure to also reserve time to set the stage for your fellow. One of the key practices during this phase is to assess your fellow’s current procedural competency. I start open-ended by asking my fellows how they have been doing with colonoscopy and then ask if they are working on a specific skill. With this information, I have a sense of how much hands-on assistance they will need, what realistic goals to set for them (e.g., navigate out of the sigmoid colon for an early learner vs. efficiently and independently completing the entire case for a later learner), and the areas to focus my observation to provide feedback after the procedure.

During this preparatory time, faculty should also discuss the patient history and indications for the procedure. Reviewing information such as prior sedation requirements and confirming plans for the procedure (e.g., random colon biopsies in a patient with chronic diarrhea and concern for microscopic colitis) helps ensure a proper plan is in place for the patient while also presenting opportunities for learning. Faculty can take this time to review the steps of a more complicated procedure (e.g., PEG placement) and establish ground rules such as when the attending will take the scope from the trainee. Lastly, make sure that the patient understands the role of the fellow and the supervision you will be providing throughout the case.
 

During the procedure

Once the procedure starts, your most important task is to maintain attention throughout the case – if you do, the other best practices generally fall into place. I am most attentive when I am gowned and positioned next to the fellow. From this vantage point, I can see the patient, the fellow’s hands, and the endoscopy screen, which allows me to readily assist if needed while directly observing the fellow’s performance.

If I need to provide feedback in the moment, I often ask the fellows to pause what they are doing and first listen to my feedback. Taking this “timeout” helps manage their cognitive load such that they can actually hear the feedback. As a general rule, however, I try to reserve the bulk of my feedback for when the procedure is complete (see next section). Another way to manage your fellow’s cognitive load is by using standardized endoscopic language throughout the procedure. For example, rather than say “go to the left” during a colonoscopy, try saying “tip left” or “torque counterclockwise” to provide more clear instructions to the fellow. Holding your fellow’s pager during the procedure is a kind gesture that also helps minimize extraneous cognitive load so that the fellow can focus on the procedure.

If your fellows get to a point where they cannot complete the task despite your giving appropriate feedback, or if patient safety concerns arise, then it is time for you to take hands-on control of the scope. In my experience, most fellows welcome the hands-on assistance as they are overloaded by the difficulty of the procedure. Setting this expectation ahead of time, as noted above, makes for a smoother transition. While assuming control of the scope, try to narrate what you are doing differently so that the fellow can still learn while watching. Once you complete the difficult portion of the procedure (e.g., reducing a loop to reach the cecum), return the scope to the fellow to maximize the hands-on participation (if time permits).
 

After the procedure

In the third and final stage of the endoscopy teaching experience, faculty should take the time to confirm the findings of the procedure with the fellow and discuss next steps in management for the patient. Finding these teachable moments helps solidify the cognitive learning for the fellow while also ensuring the patient receives the appropriate postprocedure recommendations. As part of this process, make sure to review the procedure note drafted by the fellow, and if you need to make any substantive edits, review the changes with the fellow so that he or she can learn for future cases.

To wrap up the session, provide feedback to the fellow on performance based on your direct observation. Make sure to name this process aloud – “Let’s do some feedback” – and start by asking how the fellow felt about the performance, both in terms of what went well and what the fellow would like to improve. Then provide your feedback on the performance and be specific, such as, “I really like how you identified a loop and then reduced around the hepatic flexure.” Conclude by having the fellow set a plan for improvement and make sure to ask for feedback on your own teaching performance.

In conclusion, teaching endoscopy is hard – especially as a junior attending. By breaking down the endoscopy teaching experience into its three components, however, and committing to teaching from start to finish, you can provide high-quality endoscopy education to your fellows while ensuring the best care for your patients.

Dr. Kumar is associate medicine clerkship director at Harvard Medical School, and associate physician in the division of gastroenterology at Brigham and Women’s Hospital, both in Boston. He disclosed having no conflicts of interest. He is on Twitter @NavinKumarMD.

References

1. Dilly CK and Sewell JL. 2017 Sep;153(3):632-36.

2. Waschke KA et al. Best Pract Res Clin Gastroenterol. 2016 Jun;30(3):409-19.

3. Kumar NL et al. Clin Gastroenterol Hepatol. 2020 Mar;18(3):574-79.

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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