Ten tips to help you get a research grant

It’s almost time to submit your application for the American Gastroenterological Association Research Scholar Award, the application deadline is Nov. 13, 2019. Review these tips for writing and preparing your application.

1. Start early. Allow plenty of time to complete your application, give it multiple reviews, and get feedback from others. Most applicants start working on the Specific Aims for the project 6 months in advance of the deadline.

2. Look at examples. Ask your division if there are any templates/prior grant submissions that you can review. There’s no recipe for a successful grant, so the only way to compose one is to have a sense of what has worked in the past. In general, prior awardees are happy to share their applications if you contact them.

3. Request feedback. Ask mentors and colleagues for early feedback on your Specific Aims page. If it makes sense and is interesting to them, reviewers will likely feel the same way.

4. Ask your collaborators for letters of support. In addition to your preceptor, consider including letters of support from prior researchers that you have worked with or any collaborators for the current project, especially if they will help you with a new technique or reagents.

5. Contact the grants staff with questions and concerns early on. If you don’t understand part of the application, aren’t sure if you’re eligible or are having problems with submission, contact the grant staff right away. Don’t wait until the week or day the grant is due when staff may be flooded with calls. They can assist you much better with advance notice, which will allow you to avoid last-minute stress.

6. Each application should be different. Keep in mind the scope of the grant and amount of funding. Don’t just recycle an R01-level application for a 1-year AGA pilot award.

7. More is better than less when it comes to preliminary data. If your expertise in a technique you are proposing is established, you will not need to demonstrate the capability to do the work but will likely need to show preliminary data. If you are looking to build expertise (as a part of your career development), you may need to show that the infrastructure that enables you to do the work is accessible.

8. Don’t take constructive feedback personally. As you share your draft with mentors and colleagues for feedback, you may receive some unanticipated criticism. Try not to take this personally. If you can detach yourself emotionally, you’ll be in a better position to answer critiques and make adjustments.

9. Remember your end goal: To help patients! Even the most basic science proposals are rooted in a clear potential to benefit patients.

10. Stay positive. If you do not succeed on your first application, believe in your work, make it better, and apply again.

Thanks to the following AGA Research Foundation grant recipients for sharing their advice, which resulted in the above 10 tips:

• Arthur Beyder, MD, PhD, 2015 AGA Research Scholar Award
• Barbara Jung, MD, AGAF, 2016 AGA-Elsevier Pilot Research Award
• Benjamin Lebwohl, MD, 2014 AGA Research Scholar Award
• Josephine Ni, MD, 2017 AGA-Takeda Pharmaceuticals Research Scholar Award in Inflammatory Bowel Disease
• Sahar Nissim, MD, PhD, 2017 AGA-Caroline Craig Augustyn and Damian Augustyn Award in Digestive Cancer
• Jatin Roper, MD, 2011 AGA Fellowship-to-Faculty Transition Award
• Christina Twyman-Saint Victor, MD, 2015 AGA Research Scholar Award

Visit www.gastro.org/research-funding to review the AGA Research Foundation research grants now open for applications. If you have questions about the AGA awards program, please contact [email protected].

The importance of getting involved for gastroenterology

On Sept. 20, 2019, I had the opportunity to participate in AGA’s Advocacy Day for the second time, joining 40 of our gastroenterology colleagues from across the United States on Capitol Hill to advocate for our profession and our patients.

The evening before Advocacy Day, we discussed strategies for having a successful meeting on Capitol Hill with AGA staff (including Kathleen Teixeira, AGA vice president of government affairs, and Jonathan Sollish, AGA senior coordinator, public policy). We discussed having our “asks” supported with evidence, and “getting personal” about how these policy issues directly affect us and our patients. We also had the chance to hear from Rep. Jim McGovern (D-Mass.) and Sen. Roy Blunt (R-Mo.), both of whom invited our questions. Both congressmen are friends of AGA, with Rep. McGovern serving as chair of the House Rules Committee, and Sen. Blunt serving as chair of the Senate Labor–Health & Human Services Subcommittee on Appropriations.

AGA Institute

Advocacy Day began with a group breakfast during which we reviewed some of the policy issues of central importance to gastroenterology:

• Removing Barriers to Colorectal Cancer Screening Act (HR1570/S668), which enjoys strong bipartisan support, would correct the “cost-sharing” problem of screening colonoscopies turning therapeutic (with polypectomy) for our Medicare patients, by waiving the coinsurance for screening colonoscopies — regardless of whether we remove polyps during these colonoscopies.
• Safe Step Act, HR2279, legislation introduced in the House, facilitates a common-sense and timely (72 hours or 24 hours if life threatening) appeals process when our patients are subjected to step therapy (“fail first”) by insurers.
• Improving Seniors’ Timely Access to Care Act of 2019, HR3107, legislation in the House, eases onerous prior authorization burdens by promoting an electronic prior authorization process, ensuring requests are approved by qualified medical professionals who have specialty-specific experience, and mandating that plans report their rates of delays and denials.
• National Institutes of Health research funding facilitates innovative research and supports young investigators in our field.

AGA Institute

Full of enthusiasm, our six-strong North Carolina contingent (pictured L-R, Ziad Gellad, MD, MPH, AGAF; David Leiman, MD, MSPH; Animesh Jain, MD; Anne Finefrock Peery, MD; Lisa Gangarosa, MD, AGAF, chair of the AGA Government Affairs Committee; and Amit Patel, MD) met with the offices of Rep. David Price (D-N.C.), and both North Carolina senators, Richard Burr (R) and Thom Tillis (R), on Capitol Hill to convey our “asks.”

At Rep. Price’s office in the stately Rayburn House Office Building, we thanked his team for cosponsorship of H.R. 1570 and H.R. 2279. We also discussed the importance of increasing research funding by the AGA’s goal of $2.5 billion for NIH for fiscal year 2020, noting that a majority of our delegation has received NIH funding for our training and/or research activities. We also encouraged Price’s office to cosponsor H.R. 3107, sharing our personal experiences about the administrative toll of the prior authorization process for obtaining appropriate and recommended medications for our patients – in my case, swallowed topical corticosteroids for patients with eosinophilic esophagitis.

We moved on to Sen. Tillis’s office, where we thanked his office for cosponsorship of S. 668 but encouraged his office to cosponsor upcoming companion Senate legislation for H.R. 2279 and H.R. 3107. Our colleague capably conveyed how an inflammatory bowel disease (IBD) patient he saw recently may require a colectomy because of delays in appropriate treatment stemming from these regulatory processes. We also showed Tillis’s office how NIH funding generates significant economic activity in North Carolina, supporting jobs in our state.

After a quick stop at the U.S. Senate gift shop in the basement to buy souvenirs for our kids, our last meeting was with Sen. Burr’s office. There, we also thanked his office for cosponsorship of S. 668 but encouraged him to sign the “Dear Colleague” letter that Sen. Sherrod Brown (D-Ohio) has circulated asking the Centers for Medicare & Medicaid Services to address the colonoscopy cost-sharing “loophole.” We discussed the importance of cosponsoring upcoming companion Senate legislation for H.R. 2279 and H.R. 3107, sharing stories from our clinical practices about how these regulatory burdens have delayed treatment for our patients.

You can get involved, too.

AGA Advocacy Day was a tremendous experience, but it is not the only way AGA members can get involved and take action. The AGA Advocacy website, gastro.org/advocacy, provides more information on multiple avenues for advocacy. These include an online advocacy tool for sending templated letters on these issues to your elected officials.

Perhaps now more than ever, it is crucial that we get involved to support gastroenterology and advocate for our patients.

Dr. Patel is assistant professor, division of gastroenterology, Duke University, Durham, N.C.; member, AGA Clinical Guidelines Committee.

GI of the week: Arthur Beyder, MD, PhD

Congrats to Arthur Beyder, MD, PhD, who was selected for an NIH Director’s New Innovator Award, part of the NIH director’s high-risk, high-reward research award program. The NIH Director’s New Innovator Award will provide Dr. Beyder with more than $2 million in funding over a 5-year period to continue his project: Does the gut have a sense of touch?

Dr. Beyder’s lab at the Mayo Clinic, Rochester, Minn., recently discovered a novel population of mechanosensitive epithelial sensory cells that are similar to skin’s touch sensors, which prompted a potentially transformative question: “Does the gut have a sense of touch?” We look forward to seeing the results of future research on this topic.

Dr. Beyder – a physician-scientist at the Mayo Clinic – is a 2015 AGA Research Scholar Award recipient and graduate of the 2018 AGA Future Leaders Program. Dr. Beyder currently serves on the AGA Nominating Committee.

Please join us in congratulating Dr. Beyder on Twitter (@BeyderLab) or in the AGA Community.

The NIH director’s high-risk, high-reward research program funds highly innovative, high-impact biomedical research proposed by extraordinarily creative scientists – these awards have one of the lowest funding rates for NIH. Congrats to two additional AGA members who also received a 2019 NIH Director’s New Innovator Award: Maayan Levy, PhD, and Christoph A. Thaiss, PhD, both from the University of Pennsylvania, Philadelphia.
 

Eight new insights about diet and gut health

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is so integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic: Food at the Intersection of Gut Health and Disease.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger – most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg, and soy).

3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are using self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/restrictive food intake disorder is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

6. The general population in the United States has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten, following trends, are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

7. Food can induce symptoms in patients with IBD. It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.
 

17 fellows advancing GI and patient care

Each year during Digestive Disease Week®, AGA hosts a session titled “Advancing Clinical Practice: GI Fellow-Directed Quality-Improvement Projects.” During the 2019 session, 17 quality improvement initiatives were presented — you can review these abstracts in the July issue of Gastroenterology in the “AGA Section” or review a presenter’s abstract by clicking their name or image. Kudos to the promising fellows featured below, who all served as lead authors for their quality improvement projects.

AGA Institute

Manasi Agrawal, MD
Lenox Hill Hospital, New York
@ManasiAgrawalMD

Jessica Breton, MD
Children’s Hospital of Philadelphia

Adam Faye, MD
Columbia University Medical Center, New York
@AdamFaye4

Shelly Gurwara, MD
Wake Forest Baptist Health Medical Center, Winston-Salem, N.C.

Afrin Kamal, MD
Stanford (Calif.) University

Ani Kardashian, MD
University of California, Los Angeles
@AniKardashianMD

Sonali Palchaudhuri, MD
University of Pennsylvania, Philadelphia
@sopalchaudhuri

Nasim Parsa, MD
University of Missouri Health System, Columbia

Sahil Patel, MD
Drexel University, Philadelphia
@sahilr

Vikram Raghu, MD
Children’s Hospital of Pittsburgh

Amit Shah, MD
Children’s Hospital of Philadelphia

Lin Shen, MD
Brigham and Women’s Hospital, Boston
@LinShenMD

Charles Snyder, MD
Icahn School of Medicine at Mount Sinai, New York

Brian Sullivan, MD
Duke University, Durham, N.C.

Ashley Vachon, MD
University of Colorado at Denver, Aurora

Ted Walker, MD
Washington University/Barnes Jewish Hospital, St. Louis

Xiao Jing Wang, MD
Mayo Clinic, Rochester, Minn.
@IrisWangMD

Ten tips to help you get a research grant

It’s almost time to submit your application for the American Gastroenterological Association Research Scholar Award, the application deadline is Nov. 13, 2019. Review these tips for writing and preparing your application.

1. Start early. Allow plenty of time to complete your application, give it multiple reviews, and get feedback from others. Most applicants start working on the Specific Aims for the project 6 months in advance of the deadline.

2. Look at examples. Ask your division if there are any templates/prior grant submissions that you can review. There’s no recipe for a successful grant, so the only way to compose one is to have a sense of what has worked in the past. In general, prior awardees are happy to share their applications if you contact them.

3. Request feedback. Ask mentors and colleagues for early feedback on your Specific Aims page. If it makes sense and is interesting to them, reviewers will likely feel the same way.

4. Ask your collaborators for letters of support. In addition to your preceptor, consider including letters of support from prior researchers that you have worked with or any collaborators for the current project, especially if they will help you with a new technique or reagents.

5. Contact the grants staff with questions and concerns early on. If you don’t understand part of the application, aren’t sure if you’re eligible or are having problems with submission, contact the grant staff right away. Don’t wait until the week or day the grant is due when staff may be flooded with calls. They can assist you much better with advance notice, which will allow you to avoid last-minute stress.

6. Each application should be different. Keep in mind the scope of the grant and amount of funding. Don’t just recycle an R01-level application for a 1-year AGA pilot award.

7. More is better than less when it comes to preliminary data. If your expertise in a technique you are proposing is established, you will not need to demonstrate the capability to do the work but will likely need to show preliminary data. If you are looking to build expertise (as a part of your career development), you may need to show that the infrastructure that enables you to do the work is accessible.

8. Don’t take constructive feedback personally. As you share your draft with mentors and colleagues for feedback, you may receive some unanticipated criticism. Try not to take this personally. If you can detach yourself emotionally, you’ll be in a better position to answer critiques and make adjustments.

9. Remember your end goal: To help patients! Even the most basic science proposals are rooted in a clear potential to benefit patients.

10. Stay positive. If you do not succeed on your first application, believe in your work, make it better, and apply again.

Thanks to the following AGA Research Foundation grant recipients for sharing their advice, which resulted in the above 10 tips:

• Arthur Beyder, MD, PhD, 2015 AGA Research Scholar Award
• Barbara Jung, MD, AGAF, 2016 AGA-Elsevier Pilot Research Award
• Benjamin Lebwohl, MD, 2014 AGA Research Scholar Award
• Josephine Ni, MD, 2017 AGA-Takeda Pharmaceuticals Research Scholar Award in Inflammatory Bowel Disease
• Sahar Nissim, MD, PhD, 2017 AGA-Caroline Craig Augustyn and Damian Augustyn Award in Digestive Cancer
• Jatin Roper, MD, 2011 AGA Fellowship-to-Faculty Transition Award
• Christina Twyman-Saint Victor, MD, 2015 AGA Research Scholar Award

Visit www.gastro.org/research-funding to review the AGA Research Foundation research grants now open for applications. If you have questions about the AGA awards program, please contact [email protected].

The importance of getting involved for gastroenterology

On Sept. 20, 2019, I had the opportunity to participate in AGA’s Advocacy Day for the second time, joining 40 of our gastroenterology colleagues from across the United States on Capitol Hill to advocate for our profession and our patients.

The evening before Advocacy Day, we discussed strategies for having a successful meeting on Capitol Hill with AGA staff (including Kathleen Teixeira, AGA vice president of government affairs, and Jonathan Sollish, AGA senior coordinator, public policy). We discussed having our “asks” supported with evidence, and “getting personal” about how these policy issues directly affect us and our patients. We also had the chance to hear from Rep. Jim McGovern (D-Mass.) and Sen. Roy Blunt (R-Mo.), both of whom invited our questions. Both congressmen are friends of AGA, with Rep. McGovern serving as chair of the House Rules Committee, and Sen. Blunt serving as chair of the Senate Labor–Health & Human Services Subcommittee on Appropriations.

AGA Institute

Advocacy Day began with a group breakfast during which we reviewed some of the policy issues of central importance to gastroenterology:

• Removing Barriers to Colorectal Cancer Screening Act (HR1570/S668), which enjoys strong bipartisan support, would correct the “cost-sharing” problem of screening colonoscopies turning therapeutic (with polypectomy) for our Medicare patients, by waiving the coinsurance for screening colonoscopies — regardless of whether we remove polyps during these colonoscopies.
• Safe Step Act, HR2279, legislation introduced in the House, facilitates a common-sense and timely (72 hours or 24 hours if life threatening) appeals process when our patients are subjected to step therapy (“fail first”) by insurers.
• Improving Seniors’ Timely Access to Care Act of 2019, HR3107, legislation in the House, eases onerous prior authorization burdens by promoting an electronic prior authorization process, ensuring requests are approved by qualified medical professionals who have specialty-specific experience, and mandating that plans report their rates of delays and denials.
• National Institutes of Health research funding facilitates innovative research and supports young investigators in our field.

AGA Institute

Full of enthusiasm, our six-strong North Carolina contingent (pictured L-R, Ziad Gellad, MD, MPH, AGAF; David Leiman, MD, MSPH; Animesh Jain, MD; Anne Finefrock Peery, MD; Lisa Gangarosa, MD, AGAF, chair of the AGA Government Affairs Committee; and Amit Patel, MD) met with the offices of Rep. David Price (D-N.C.), and both North Carolina senators, Richard Burr (R) and Thom Tillis (R), on Capitol Hill to convey our “asks.”

At Rep. Price’s office in the stately Rayburn House Office Building, we thanked his team for cosponsorship of H.R. 1570 and H.R. 2279. We also discussed the importance of increasing research funding by the AGA’s goal of $2.5 billion for NIH for fiscal year 2020, noting that a majority of our delegation has received NIH funding for our training and/or research activities. We also encouraged Price’s office to cosponsor H.R. 3107, sharing our personal experiences about the administrative toll of the prior authorization process for obtaining appropriate and recommended medications for our patients – in my case, swallowed topical corticosteroids for patients with eosinophilic esophagitis.

We moved on to Sen. Tillis’s office, where we thanked his office for cosponsorship of S. 668 but encouraged his office to cosponsor upcoming companion Senate legislation for H.R. 2279 and H.R. 3107. Our colleague capably conveyed how an inflammatory bowel disease (IBD) patient he saw recently may require a colectomy because of delays in appropriate treatment stemming from these regulatory processes. We also showed Tillis’s office how NIH funding generates significant economic activity in North Carolina, supporting jobs in our state.

After a quick stop at the U.S. Senate gift shop in the basement to buy souvenirs for our kids, our last meeting was with Sen. Burr’s office. There, we also thanked his office for cosponsorship of S. 668 but encouraged him to sign the “Dear Colleague” letter that Sen. Sherrod Brown (D-Ohio) has circulated asking the Centers for Medicare & Medicaid Services to address the colonoscopy cost-sharing “loophole.” We discussed the importance of cosponsoring upcoming companion Senate legislation for H.R. 2279 and H.R. 3107, sharing stories from our clinical practices about how these regulatory burdens have delayed treatment for our patients.

You can get involved, too.

AGA Advocacy Day was a tremendous experience, but it is not the only way AGA members can get involved and take action. The AGA Advocacy website, gastro.org/advocacy, provides more information on multiple avenues for advocacy. These include an online advocacy tool for sending templated letters on these issues to your elected officials.

Perhaps now more than ever, it is crucial that we get involved to support gastroenterology and advocate for our patients.

Dr. Patel is assistant professor, division of gastroenterology, Duke University, Durham, N.C.; member, AGA Clinical Guidelines Committee.

GI of the week: Arthur Beyder, MD, PhD

Congrats to Arthur Beyder, MD, PhD, who was selected for an NIH Director’s New Innovator Award, part of the NIH director’s high-risk, high-reward research award program. The NIH Director’s New Innovator Award will provide Dr. Beyder with more than $2 million in funding over a 5-year period to continue his project: Does the gut have a sense of touch?

Dr. Beyder’s lab at the Mayo Clinic, Rochester, Minn., recently discovered a novel population of mechanosensitive epithelial sensory cells that are similar to skin’s touch sensors, which prompted a potentially transformative question: “Does the gut have a sense of touch?” We look forward to seeing the results of future research on this topic.

Dr. Beyder – a physician-scientist at the Mayo Clinic – is a 2015 AGA Research Scholar Award recipient and graduate of the 2018 AGA Future Leaders Program. Dr. Beyder currently serves on the AGA Nominating Committee.

Please join us in congratulating Dr. Beyder on Twitter (@BeyderLab) or in the AGA Community.

The NIH director’s high-risk, high-reward research program funds highly innovative, high-impact biomedical research proposed by extraordinarily creative scientists – these awards have one of the lowest funding rates for NIH. Congrats to two additional AGA members who also received a 2019 NIH Director’s New Innovator Award: Maayan Levy, PhD, and Christoph A. Thaiss, PhD, both from the University of Pennsylvania, Philadelphia.
 

Eight new insights about diet and gut health

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is so integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic: Food at the Intersection of Gut Health and Disease.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger – most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg, and soy).

3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are using self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/restrictive food intake disorder is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

6. The general population in the United States has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten, following trends, are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

7. Food can induce symptoms in patients with IBD. It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.
 

17 fellows advancing GI and patient care

Each year during Digestive Disease Week®, AGA hosts a session titled “Advancing Clinical Practice: GI Fellow-Directed Quality-Improvement Projects.” During the 2019 session, 17 quality improvement initiatives were presented — you can review these abstracts in the July issue of Gastroenterology in the “AGA Section” or review a presenter’s abstract by clicking their name or image. Kudos to the promising fellows featured below, who all served as lead authors for their quality improvement projects.

AGA Institute

Manasi Agrawal, MD
Lenox Hill Hospital, New York
@ManasiAgrawalMD

Jessica Breton, MD
Children’s Hospital of Philadelphia

Adam Faye, MD
Columbia University Medical Center, New York
@AdamFaye4

Shelly Gurwara, MD
Wake Forest Baptist Health Medical Center, Winston-Salem, N.C.

Afrin Kamal, MD
Stanford (Calif.) University

Ani Kardashian, MD
University of California, Los Angeles
@AniKardashianMD

Sonali Palchaudhuri, MD
University of Pennsylvania, Philadelphia
@sopalchaudhuri

Nasim Parsa, MD
University of Missouri Health System, Columbia

Sahil Patel, MD
Drexel University, Philadelphia
@sahilr

Vikram Raghu, MD
Children’s Hospital of Pittsburgh

Amit Shah, MD
Children’s Hospital of Philadelphia

Lin Shen, MD
Brigham and Women’s Hospital, Boston
@LinShenMD

Charles Snyder, MD
Icahn School of Medicine at Mount Sinai, New York

Brian Sullivan, MD
Duke University, Durham, N.C.

Ashley Vachon, MD
University of Colorado at Denver, Aurora

Ted Walker, MD
Washington University/Barnes Jewish Hospital, St. Louis

Xiao Jing Wang, MD
Mayo Clinic, Rochester, Minn.
@IrisWangMD

Ten tips to help you get a research grant

It’s almost time to submit your application for the American Gastroenterological Association Research Scholar Award, the application deadline is Nov. 13, 2019. Review these tips for writing and preparing your application.

1. Start early. Allow plenty of time to complete your application, give it multiple reviews, and get feedback from others. Most applicants start working on the Specific Aims for the project 6 months in advance of the deadline.

2. Look at examples. Ask your division if there are any templates/prior grant submissions that you can review. There’s no recipe for a successful grant, so the only way to compose one is to have a sense of what has worked in the past. In general, prior awardees are happy to share their applications if you contact them.

3. Request feedback. Ask mentors and colleagues for early feedback on your Specific Aims page. If it makes sense and is interesting to them, reviewers will likely feel the same way.

4. Ask your collaborators for letters of support. In addition to your preceptor, consider including letters of support from prior researchers that you have worked with or any collaborators for the current project, especially if they will help you with a new technique or reagents.

5. Contact the grants staff with questions and concerns early on. If you don’t understand part of the application, aren’t sure if you’re eligible or are having problems with submission, contact the grant staff right away. Don’t wait until the week or day the grant is due when staff may be flooded with calls. They can assist you much better with advance notice, which will allow you to avoid last-minute stress.

6. Each application should be different. Keep in mind the scope of the grant and amount of funding. Don’t just recycle an R01-level application for a 1-year AGA pilot award.

7. More is better than less when it comes to preliminary data. If your expertise in a technique you are proposing is established, you will not need to demonstrate the capability to do the work but will likely need to show preliminary data. If you are looking to build expertise (as a part of your career development), you may need to show that the infrastructure that enables you to do the work is accessible.

8. Don’t take constructive feedback personally. As you share your draft with mentors and colleagues for feedback, you may receive some unanticipated criticism. Try not to take this personally. If you can detach yourself emotionally, you’ll be in a better position to answer critiques and make adjustments.

9. Remember your end goal: To help patients! Even the most basic science proposals are rooted in a clear potential to benefit patients.

10. Stay positive. If you do not succeed on your first application, believe in your work, make it better, and apply again.

Thanks to the following AGA Research Foundation grant recipients for sharing their advice, which resulted in the above 10 tips:

• Arthur Beyder, MD, PhD, 2015 AGA Research Scholar Award
• Barbara Jung, MD, AGAF, 2016 AGA-Elsevier Pilot Research Award
• Benjamin Lebwohl, MD, 2014 AGA Research Scholar Award
• Josephine Ni, MD, 2017 AGA-Takeda Pharmaceuticals Research Scholar Award in Inflammatory Bowel Disease
• Sahar Nissim, MD, PhD, 2017 AGA-Caroline Craig Augustyn and Damian Augustyn Award in Digestive Cancer
• Jatin Roper, MD, 2011 AGA Fellowship-to-Faculty Transition Award
• Christina Twyman-Saint Victor, MD, 2015 AGA Research Scholar Award

Visit www.gastro.org/research-funding to review the AGA Research Foundation research grants now open for applications. If you have questions about the AGA awards program, please contact [email protected].

The importance of getting involved for gastroenterology

On Sept. 20, 2019, I had the opportunity to participate in AGA’s Advocacy Day for the second time, joining 40 of our gastroenterology colleagues from across the United States on Capitol Hill to advocate for our profession and our patients.

The evening before Advocacy Day, we discussed strategies for having a successful meeting on Capitol Hill with AGA staff (including Kathleen Teixeira, AGA vice president of government affairs, and Jonathan Sollish, AGA senior coordinator, public policy). We discussed having our “asks” supported with evidence, and “getting personal” about how these policy issues directly affect us and our patients. We also had the chance to hear from Rep. Jim McGovern (D-Mass.) and Sen. Roy Blunt (R-Mo.), both of whom invited our questions. Both congressmen are friends of AGA, with Rep. McGovern serving as chair of the House Rules Committee, and Sen. Blunt serving as chair of the Senate Labor–Health & Human Services Subcommittee on Appropriations.

AGA Institute

Advocacy Day began with a group breakfast during which we reviewed some of the policy issues of central importance to gastroenterology:

• Removing Barriers to Colorectal Cancer Screening Act (HR1570/S668), which enjoys strong bipartisan support, would correct the “cost-sharing” problem of screening colonoscopies turning therapeutic (with polypectomy) for our Medicare patients, by waiving the coinsurance for screening colonoscopies — regardless of whether we remove polyps during these colonoscopies.
• Safe Step Act, HR2279, legislation introduced in the House, facilitates a common-sense and timely (72 hours or 24 hours if life threatening) appeals process when our patients are subjected to step therapy (“fail first”) by insurers.
• Improving Seniors’ Timely Access to Care Act of 2019, HR3107, legislation in the House, eases onerous prior authorization burdens by promoting an electronic prior authorization process, ensuring requests are approved by qualified medical professionals who have specialty-specific experience, and mandating that plans report their rates of delays and denials.
• National Institutes of Health research funding facilitates innovative research and supports young investigators in our field.

AGA Institute

Full of enthusiasm, our six-strong North Carolina contingent (pictured L-R, Ziad Gellad, MD, MPH, AGAF; David Leiman, MD, MSPH; Animesh Jain, MD; Anne Finefrock Peery, MD; Lisa Gangarosa, MD, AGAF, chair of the AGA Government Affairs Committee; and Amit Patel, MD) met with the offices of Rep. David Price (D-N.C.), and both North Carolina senators, Richard Burr (R) and Thom Tillis (R), on Capitol Hill to convey our “asks.”

At Rep. Price’s office in the stately Rayburn House Office Building, we thanked his team for cosponsorship of H.R. 1570 and H.R. 2279. We also discussed the importance of increasing research funding by the AGA’s goal of $2.5 billion for NIH for fiscal year 2020, noting that a majority of our delegation has received NIH funding for our training and/or research activities. We also encouraged Price’s office to cosponsor H.R. 3107, sharing our personal experiences about the administrative toll of the prior authorization process for obtaining appropriate and recommended medications for our patients – in my case, swallowed topical corticosteroids for patients with eosinophilic esophagitis.

We moved on to Sen. Tillis’s office, where we thanked his office for cosponsorship of S. 668 but encouraged his office to cosponsor upcoming companion Senate legislation for H.R. 2279 and H.R. 3107. Our colleague capably conveyed how an inflammatory bowel disease (IBD) patient he saw recently may require a colectomy because of delays in appropriate treatment stemming from these regulatory processes. We also showed Tillis’s office how NIH funding generates significant economic activity in North Carolina, supporting jobs in our state.

After a quick stop at the U.S. Senate gift shop in the basement to buy souvenirs for our kids, our last meeting was with Sen. Burr’s office. There, we also thanked his office for cosponsorship of S. 668 but encouraged him to sign the “Dear Colleague” letter that Sen. Sherrod Brown (D-Ohio) has circulated asking the Centers for Medicare & Medicaid Services to address the colonoscopy cost-sharing “loophole.” We discussed the importance of cosponsoring upcoming companion Senate legislation for H.R. 2279 and H.R. 3107, sharing stories from our clinical practices about how these regulatory burdens have delayed treatment for our patients.

You can get involved, too.

AGA Advocacy Day was a tremendous experience, but it is not the only way AGA members can get involved and take action. The AGA Advocacy website, gastro.org/advocacy, provides more information on multiple avenues for advocacy. These include an online advocacy tool for sending templated letters on these issues to your elected officials.

Perhaps now more than ever, it is crucial that we get involved to support gastroenterology and advocate for our patients.

Dr. Patel is assistant professor, division of gastroenterology, Duke University, Durham, N.C.; member, AGA Clinical Guidelines Committee.

GI of the week: Arthur Beyder, MD, PhD

Congrats to Arthur Beyder, MD, PhD, who was selected for an NIH Director’s New Innovator Award, part of the NIH director’s high-risk, high-reward research award program. The NIH Director’s New Innovator Award will provide Dr. Beyder with more than $2 million in funding over a 5-year period to continue his project: Does the gut have a sense of touch?

Dr. Beyder’s lab at the Mayo Clinic, Rochester, Minn., recently discovered a novel population of mechanosensitive epithelial sensory cells that are similar to skin’s touch sensors, which prompted a potentially transformative question: “Does the gut have a sense of touch?” We look forward to seeing the results of future research on this topic.

Dr. Beyder – a physician-scientist at the Mayo Clinic – is a 2015 AGA Research Scholar Award recipient and graduate of the 2018 AGA Future Leaders Program. Dr. Beyder currently serves on the AGA Nominating Committee.

Please join us in congratulating Dr. Beyder on Twitter (@BeyderLab) or in the AGA Community.

The NIH director’s high-risk, high-reward research program funds highly innovative, high-impact biomedical research proposed by extraordinarily creative scientists – these awards have one of the lowest funding rates for NIH. Congrats to two additional AGA members who also received a 2019 NIH Director’s New Innovator Award: Maayan Levy, PhD, and Christoph A. Thaiss, PhD, both from the University of Pennsylvania, Philadelphia.
 

Eight new insights about diet and gut health

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is so integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic: Food at the Intersection of Gut Health and Disease.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger – most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg, and soy).

3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are using self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/restrictive food intake disorder is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

6. The general population in the United States has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten, following trends, are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

7. Food can induce symptoms in patients with IBD. It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.
 

17 fellows advancing GI and patient care

Each year during Digestive Disease Week®, AGA hosts a session titled “Advancing Clinical Practice: GI Fellow-Directed Quality-Improvement Projects.” During the 2019 session, 17 quality improvement initiatives were presented — you can review these abstracts in the July issue of Gastroenterology in the “AGA Section” or review a presenter’s abstract by clicking their name or image. Kudos to the promising fellows featured below, who all served as lead authors for their quality improvement projects.

AGA Institute

Manasi Agrawal, MD
Lenox Hill Hospital, New York
@ManasiAgrawalMD

Jessica Breton, MD
Children’s Hospital of Philadelphia

Adam Faye, MD
Columbia University Medical Center, New York
@AdamFaye4

Shelly Gurwara, MD
Wake Forest Baptist Health Medical Center, Winston-Salem, N.C.

Afrin Kamal, MD
Stanford (Calif.) University

Ani Kardashian, MD
University of California, Los Angeles
@AniKardashianMD

Sonali Palchaudhuri, MD
University of Pennsylvania, Philadelphia
@sopalchaudhuri

Nasim Parsa, MD
University of Missouri Health System, Columbia

Sahil Patel, MD
Drexel University, Philadelphia
@sahilr

Vikram Raghu, MD
Children’s Hospital of Pittsburgh

Amit Shah, MD
Children’s Hospital of Philadelphia

Lin Shen, MD
Brigham and Women’s Hospital, Boston
@LinShenMD

Charles Snyder, MD
Icahn School of Medicine at Mount Sinai, New York

Brian Sullivan, MD
Duke University, Durham, N.C.

Ashley Vachon, MD
University of Colorado at Denver, Aurora

Ted Walker, MD
Washington University/Barnes Jewish Hospital, St. Louis

Xiao Jing Wang, MD
Mayo Clinic, Rochester, Minn.
@IrisWangMD

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

SAN DIEGO – The Food and Drug Administration has not approved a drug to treat agitation in dementia, and the absence of medication candidates is only part of the picture. As a geriatric psychiatrist explained to colleagues, the FDA has not taken the step of recognizing that the condition exists. But there are still options to treat this dangerous disorder – although none is ideal.

Research into efficacy of potential treatments for agitation is limited, variable, and “have high placebo effects,” said Marc E. Agronin, MD, of the MIND Institute and Miami Jewish Health, at the annual Psych Congress. “There is no one single magic bullet, especially since there are so many manifestations of agitation, and there are side effects of medication. This is a tough area to focus on.”

What can clinicians do? Dr. Agronin recommended starting with the steps in the DICE algorithm.

• Describe: Learn about the aspects of agitation by talking to caregivers and understanding the circumstances when symptoms develop.
• Investigate: Identify contributing factors, such as those related to illness, medication, and the environment.
• Create: Come up with a team strategy to address the contributing factors. Address the most urgent risks first, such as danger to self or others, which can require quick action – such as medication adjustment, an ED visit, or psychiatric hospitalization. Delirium is especially dangerous since it can lead to injury and subacute cognitive decline. And keep in mind, Dr. Agorin said, that it may be risky to do nothing or undertreat.
• Evaluate: Track the results of the strategy while realizing that there’s “not always a quick fix.” Research suggests that therapeutic approaches such as music, aromatherapy, exercise, group activities, hand massage, and thermal baths can be helpful, Dr. Agronin said.

As for medications, he advised starting with lower doses, perhaps 50%, because older people are less tolerant of medication. And beware of oversedation, dizziness, and lowered blood pressure, which can lead to falls. A hip fracture can “spiral down to someone’s demise very quickly,” he said.

Here’s a closer look at Dr. Agronin’s comments regarding specific medications.

• Antipsychotics: “Every antipsychotic has been used for agitation,” he said, “and they probably have the best efficacy,” compared with other drugs. But the risk of side effects is moderate to high, and atypical antipsychotics have a black-box warning about their use in dementia-related psychosis in elderly patients. Also, discontinuation of antipsychotics can trigger worsening symptoms in some patients. There has been tremendous controversy in recent years over the use of antipsychotics in older patients, but other drugs might be less effective than antipsychotics while still having similar side effect profiles, he said. And clinicians might be too cautious about doses even when they do use these drugs.
• Benzodiazepines: They can work quickly but come with a risk of sedation. Trazodone is an “excellent” alternative to reduce agitation in the short-term, he said.
• Antidepressants: These drugs can address underlying depression. Study results have been mixed.
• Mood stabilizers: Study results are mixed. “Unfortunately, in many situations [clinicians] get scared away from antipsychotics and use mood stabilizers, but there is less data for them in terms of efficacy, and there are a lot of side effects that have to be monitored,” he said.

Dr. Agronin is the author of “How We Age” (Da Capo Lifelong Books, 2012) and “The End of Old Age” (Da Capo Lifelong Books, 2018). He has no relevant disclosures.

SAN DIEGO – The Food and Drug Administration has not approved a drug to treat agitation in dementia, and the absence of medication candidates is only part of the picture. As a geriatric psychiatrist explained to colleagues, the FDA has not taken the step of recognizing that the condition exists. But there are still options to treat this dangerous disorder – although none is ideal.

Research into efficacy of potential treatments for agitation is limited, variable, and “have high placebo effects,” said Marc E. Agronin, MD, of the MIND Institute and Miami Jewish Health, at the annual Psych Congress. “There is no one single magic bullet, especially since there are so many manifestations of agitation, and there are side effects of medication. This is a tough area to focus on.”

What can clinicians do? Dr. Agronin recommended starting with the steps in the DICE algorithm.

• Describe: Learn about the aspects of agitation by talking to caregivers and understanding the circumstances when symptoms develop.
• Investigate: Identify contributing factors, such as those related to illness, medication, and the environment.
• Create: Come up with a team strategy to address the contributing factors. Address the most urgent risks first, such as danger to self or others, which can require quick action – such as medication adjustment, an ED visit, or psychiatric hospitalization. Delirium is especially dangerous since it can lead to injury and subacute cognitive decline. And keep in mind, Dr. Agorin said, that it may be risky to do nothing or undertreat.
• Evaluate: Track the results of the strategy while realizing that there’s “not always a quick fix.” Research suggests that therapeutic approaches such as music, aromatherapy, exercise, group activities, hand massage, and thermal baths can be helpful, Dr. Agronin said.

As for medications, he advised starting with lower doses, perhaps 50%, because older people are less tolerant of medication. And beware of oversedation, dizziness, and lowered blood pressure, which can lead to falls. A hip fracture can “spiral down to someone’s demise very quickly,” he said.

Here’s a closer look at Dr. Agronin’s comments regarding specific medications.

• Antipsychotics: “Every antipsychotic has been used for agitation,” he said, “and they probably have the best efficacy,” compared with other drugs. But the risk of side effects is moderate to high, and atypical antipsychotics have a black-box warning about their use in dementia-related psychosis in elderly patients. Also, discontinuation of antipsychotics can trigger worsening symptoms in some patients. There has been tremendous controversy in recent years over the use of antipsychotics in older patients, but other drugs might be less effective than antipsychotics while still having similar side effect profiles, he said. And clinicians might be too cautious about doses even when they do use these drugs.
• Benzodiazepines: They can work quickly but come with a risk of sedation. Trazodone is an “excellent” alternative to reduce agitation in the short-term, he said.
• Antidepressants: These drugs can address underlying depression. Study results have been mixed.
• Mood stabilizers: Study results are mixed. “Unfortunately, in many situations [clinicians] get scared away from antipsychotics and use mood stabilizers, but there is less data for them in terms of efficacy, and there are a lot of side effects that have to be monitored,” he said.

Dr. Agronin is the author of “How We Age” (Da Capo Lifelong Books, 2012) and “The End of Old Age” (Da Capo Lifelong Books, 2018). He has no relevant disclosures.

SAN DIEGO – The Food and Drug Administration has not approved a drug to treat agitation in dementia, and the absence of medication candidates is only part of the picture. As a geriatric psychiatrist explained to colleagues, the FDA has not taken the step of recognizing that the condition exists. But there are still options to treat this dangerous disorder – although none is ideal.

Research into efficacy of potential treatments for agitation is limited, variable, and “have high placebo effects,” said Marc E. Agronin, MD, of the MIND Institute and Miami Jewish Health, at the annual Psych Congress. “There is no one single magic bullet, especially since there are so many manifestations of agitation, and there are side effects of medication. This is a tough area to focus on.”

What can clinicians do? Dr. Agronin recommended starting with the steps in the DICE algorithm.

• Describe: Learn about the aspects of agitation by talking to caregivers and understanding the circumstances when symptoms develop.
• Investigate: Identify contributing factors, such as those related to illness, medication, and the environment.
• Create: Come up with a team strategy to address the contributing factors. Address the most urgent risks first, such as danger to self or others, which can require quick action – such as medication adjustment, an ED visit, or psychiatric hospitalization. Delirium is especially dangerous since it can lead to injury and subacute cognitive decline. And keep in mind, Dr. Agorin said, that it may be risky to do nothing or undertreat.
• Evaluate: Track the results of the strategy while realizing that there’s “not always a quick fix.” Research suggests that therapeutic approaches such as music, aromatherapy, exercise, group activities, hand massage, and thermal baths can be helpful, Dr. Agronin said.

As for medications, he advised starting with lower doses, perhaps 50%, because older people are less tolerant of medication. And beware of oversedation, dizziness, and lowered blood pressure, which can lead to falls. A hip fracture can “spiral down to someone’s demise very quickly,” he said.

Here’s a closer look at Dr. Agronin’s comments regarding specific medications.

• Antipsychotics: “Every antipsychotic has been used for agitation,” he said, “and they probably have the best efficacy,” compared with other drugs. But the risk of side effects is moderate to high, and atypical antipsychotics have a black-box warning about their use in dementia-related psychosis in elderly patients. Also, discontinuation of antipsychotics can trigger worsening symptoms in some patients. There has been tremendous controversy in recent years over the use of antipsychotics in older patients, but other drugs might be less effective than antipsychotics while still having similar side effect profiles, he said. And clinicians might be too cautious about doses even when they do use these drugs.
• Benzodiazepines: They can work quickly but come with a risk of sedation. Trazodone is an “excellent” alternative to reduce agitation in the short-term, he said.
• Antidepressants: These drugs can address underlying depression. Study results have been mixed.
• Mood stabilizers: Study results are mixed. “Unfortunately, in many situations [clinicians] get scared away from antipsychotics and use mood stabilizers, but there is less data for them in terms of efficacy, and there are a lot of side effects that have to be monitored,” he said.

Dr. Agronin is the author of “How We Age” (Da Capo Lifelong Books, 2012) and “The End of Old Age” (Da Capo Lifelong Books, 2018). He has no relevant disclosures.

EDINBURGH – Routine empiric prophylaxis against pneumocystis jiroveci pneumonia (PJP) may be unwarranted in chronic lymphocytic leukemia patients initiating Bruton tyrosine kinase (BTK) inhibitor therapy, a retrospective chart review suggests.

Among 212 patients with chronic lymphocytic leukemia (CLL) who were treated with ibrutinib or acalabrutinib either as monotherapy or as part of a combination regimen for at least 30 days between Jan. 1, 2010, and Feb. 1, 2019, at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, 125 (59%) received PJP prophylaxis, including either trimethoprim-sulfamethoxazole (74%) or atovaquone (26%), Christine Ryan, MD, reported at the International Workshop on CLL.

Two PJP cases occurred in the 120 patients on single-agent ibrutinib, including one in a previously untreated patient and one in a patient with relapsed/refractory CLL. Neither patient had received PJP prophylaxis, said Dr. Ryan, a senior resident at Brigham and Women’s Hospital.

No PJP cases occurred in the 21 patients who received acalabrutinib monotherapy or in the 14 patients who received acalabrutinib combination therapy, and 1 occurred in a trial cohort of 57 patients receiving frontline ibrutinib plus fludarabine-based chemotherapy (FCR). The latter had been prescribed PJP prophylaxis, but “unfortunately self-discontinued the prophylaxis” 2 months prior to the infection, Dr. Ryan said.

“The overall prevalence of PJP in patients not on prophylaxis was 3.4%, there were no cases of PJP in patients on prophylaxis, and the incidence rate in patients not on prophylaxis was 1.9 per 100 person-years, with a number needed to treat to prevent 1 case of PJP calculated to be 42 patients,” she said.

In addition to PJP, three cases of proven or probable invasive fungal infections (IFI) occurred, including one case of pulmonary histoplasmosis in the ibrutinib plus FCR trial cohort and two cases of aspergillosis, including a pulmonary case and a brain abscess, in an ibrutinib plus umbralisib trial cohort.

“The overall prevalence of aspergillosis or histoplasmosis in our entire cohort was 1.4%, and notably there were no cases of IFI in the single-agent therapy cohort, but the prevalence in the ibrutinib-combination therapy patients was 4.2%,” Dr. Ryan said.

Patients included in the review were adults with a median age of 64.8 years, and 64% were men. The median duration of BTK inhibitor therapy was 23.2 months.

“We know that CLL patients treated with fludarabine have an increased risk of PJP,” she said. “As such, it is routinely recommended that patients receiving fludarabine-containing chemotherapy regimens are prescribed PJP prophylaxis.”

Additionally, the increasing use of oral BTK inhibitors has raised concerns about the potential risk of PJP or other IFIs in patients on those agents, Dr. Ryan explained, noting that existing case reports and case series looking at PJP have shown varying prevalence rates, and little is known about the effects of prophylaxis.

“At present, there are no international guidelines regarding the use of antimicrobial prophylaxis in CLL patients treated with BTK inhibitors, and prophylaxis practices vary widely across countries and institutions,” she said.

The findings of the current study demonstrate that such variation exists “even within our own institution,” Dr. Ryan added.

The findings also show an overall low PJP prevalence of 3.4% in patients not receiving prophylaxis, which falls below the “commonly accepted threshold of 5%, above which routine prophylaxis becomes recommended,” she said.

“Overall, our data suggest that routine PJP or IFI prophylaxis in patients receiving BTK inhibitors may not be needed, but this is definitely an area that requires further study, ideally with a prospective trial with a larger sample size and multiple institutions, to support the development of consensus guidelines on this issue,” she said.

Dr. Ryan reported having no financial disclosures.

[email protected]

EDINBURGH – Routine empiric prophylaxis against pneumocystis jiroveci pneumonia (PJP) may be unwarranted in chronic lymphocytic leukemia patients initiating Bruton tyrosine kinase (BTK) inhibitor therapy, a retrospective chart review suggests.

Among 212 patients with chronic lymphocytic leukemia (CLL) who were treated with ibrutinib or acalabrutinib either as monotherapy or as part of a combination regimen for at least 30 days between Jan. 1, 2010, and Feb. 1, 2019, at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, 125 (59%) received PJP prophylaxis, including either trimethoprim-sulfamethoxazole (74%) or atovaquone (26%), Christine Ryan, MD, reported at the International Workshop on CLL.

Two PJP cases occurred in the 120 patients on single-agent ibrutinib, including one in a previously untreated patient and one in a patient with relapsed/refractory CLL. Neither patient had received PJP prophylaxis, said Dr. Ryan, a senior resident at Brigham and Women’s Hospital.

No PJP cases occurred in the 21 patients who received acalabrutinib monotherapy or in the 14 patients who received acalabrutinib combination therapy, and 1 occurred in a trial cohort of 57 patients receiving frontline ibrutinib plus fludarabine-based chemotherapy (FCR). The latter had been prescribed PJP prophylaxis, but “unfortunately self-discontinued the prophylaxis” 2 months prior to the infection, Dr. Ryan said.

“The overall prevalence of PJP in patients not on prophylaxis was 3.4%, there were no cases of PJP in patients on prophylaxis, and the incidence rate in patients not on prophylaxis was 1.9 per 100 person-years, with a number needed to treat to prevent 1 case of PJP calculated to be 42 patients,” she said.

In addition to PJP, three cases of proven or probable invasive fungal infections (IFI) occurred, including one case of pulmonary histoplasmosis in the ibrutinib plus FCR trial cohort and two cases of aspergillosis, including a pulmonary case and a brain abscess, in an ibrutinib plus umbralisib trial cohort.

“The overall prevalence of aspergillosis or histoplasmosis in our entire cohort was 1.4%, and notably there were no cases of IFI in the single-agent therapy cohort, but the prevalence in the ibrutinib-combination therapy patients was 4.2%,” Dr. Ryan said.

Patients included in the review were adults with a median age of 64.8 years, and 64% were men. The median duration of BTK inhibitor therapy was 23.2 months.

“We know that CLL patients treated with fludarabine have an increased risk of PJP,” she said. “As such, it is routinely recommended that patients receiving fludarabine-containing chemotherapy regimens are prescribed PJP prophylaxis.”

Additionally, the increasing use of oral BTK inhibitors has raised concerns about the potential risk of PJP or other IFIs in patients on those agents, Dr. Ryan explained, noting that existing case reports and case series looking at PJP have shown varying prevalence rates, and little is known about the effects of prophylaxis.

“At present, there are no international guidelines regarding the use of antimicrobial prophylaxis in CLL patients treated with BTK inhibitors, and prophylaxis practices vary widely across countries and institutions,” she said.

The findings of the current study demonstrate that such variation exists “even within our own institution,” Dr. Ryan added.

The findings also show an overall low PJP prevalence of 3.4% in patients not receiving prophylaxis, which falls below the “commonly accepted threshold of 5%, above which routine prophylaxis becomes recommended,” she said.

“Overall, our data suggest that routine PJP or IFI prophylaxis in patients receiving BTK inhibitors may not be needed, but this is definitely an area that requires further study, ideally with a prospective trial with a larger sample size and multiple institutions, to support the development of consensus guidelines on this issue,” she said.

Dr. Ryan reported having no financial disclosures.

[email protected]

EDINBURGH – Routine empiric prophylaxis against pneumocystis jiroveci pneumonia (PJP) may be unwarranted in chronic lymphocytic leukemia patients initiating Bruton tyrosine kinase (BTK) inhibitor therapy, a retrospective chart review suggests.

Among 212 patients with chronic lymphocytic leukemia (CLL) who were treated with ibrutinib or acalabrutinib either as monotherapy or as part of a combination regimen for at least 30 days between Jan. 1, 2010, and Feb. 1, 2019, at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, 125 (59%) received PJP prophylaxis, including either trimethoprim-sulfamethoxazole (74%) or atovaquone (26%), Christine Ryan, MD, reported at the International Workshop on CLL.

Two PJP cases occurred in the 120 patients on single-agent ibrutinib, including one in a previously untreated patient and one in a patient with relapsed/refractory CLL. Neither patient had received PJP prophylaxis, said Dr. Ryan, a senior resident at Brigham and Women’s Hospital.

No PJP cases occurred in the 21 patients who received acalabrutinib monotherapy or in the 14 patients who received acalabrutinib combination therapy, and 1 occurred in a trial cohort of 57 patients receiving frontline ibrutinib plus fludarabine-based chemotherapy (FCR). The latter had been prescribed PJP prophylaxis, but “unfortunately self-discontinued the prophylaxis” 2 months prior to the infection, Dr. Ryan said.

“The overall prevalence of PJP in patients not on prophylaxis was 3.4%, there were no cases of PJP in patients on prophylaxis, and the incidence rate in patients not on prophylaxis was 1.9 per 100 person-years, with a number needed to treat to prevent 1 case of PJP calculated to be 42 patients,” she said.

In addition to PJP, three cases of proven or probable invasive fungal infections (IFI) occurred, including one case of pulmonary histoplasmosis in the ibrutinib plus FCR trial cohort and two cases of aspergillosis, including a pulmonary case and a brain abscess, in an ibrutinib plus umbralisib trial cohort.

“The overall prevalence of aspergillosis or histoplasmosis in our entire cohort was 1.4%, and notably there were no cases of IFI in the single-agent therapy cohort, but the prevalence in the ibrutinib-combination therapy patients was 4.2%,” Dr. Ryan said.

Patients included in the review were adults with a median age of 64.8 years, and 64% were men. The median duration of BTK inhibitor therapy was 23.2 months.

“We know that CLL patients treated with fludarabine have an increased risk of PJP,” she said. “As such, it is routinely recommended that patients receiving fludarabine-containing chemotherapy regimens are prescribed PJP prophylaxis.”

Additionally, the increasing use of oral BTK inhibitors has raised concerns about the potential risk of PJP or other IFIs in patients on those agents, Dr. Ryan explained, noting that existing case reports and case series looking at PJP have shown varying prevalence rates, and little is known about the effects of prophylaxis.

“At present, there are no international guidelines regarding the use of antimicrobial prophylaxis in CLL patients treated with BTK inhibitors, and prophylaxis practices vary widely across countries and institutions,” she said.

The findings of the current study demonstrate that such variation exists “even within our own institution,” Dr. Ryan added.

The findings also show an overall low PJP prevalence of 3.4% in patients not receiving prophylaxis, which falls below the “commonly accepted threshold of 5%, above which routine prophylaxis becomes recommended,” she said.

“Overall, our data suggest that routine PJP or IFI prophylaxis in patients receiving BTK inhibitors may not be needed, but this is definitely an area that requires further study, ideally with a prospective trial with a larger sample size and multiple institutions, to support the development of consensus guidelines on this issue,” she said.

Dr. Ryan reported having no financial disclosures.

[email protected]

It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont;  VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.

In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.

Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.

The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.

However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.

Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.

Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.

The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.

The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.

Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.

Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.

It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont;  VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.

In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.

Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.

The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.

However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.

Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.

Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.

The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.

The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.

Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.

Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.

It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont;  VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.

In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.

Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.

The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.

However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.

Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.

Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.

The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.

The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.

Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.

Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.