The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]

WAIKOLOA, HAWAII – One of the most important steps in treating secondary infections in children with atopic dermatitis (AD) is bringing the eczema under control, according to Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at the University of California, San Diego.

It’s the breach in skin integrity that gives skin flora – most commonly Staphylococcus or Streptococcus – an opening for infection.

Dr. Eichenfield shared his treatment approach in a pearl-filled interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“Many times, anti-inflammatories are going to be the effective therapy,” whether topical steroids or systemic therapies. But with a secondary infection, systemic antibiotics are in order, too, but topical ones aren’t much use, he said.

Dr. Eichenfield gets a lot of questions about steroid-sparing options for very young children, since topical calcineurin inhibitors and the like aren’t approved in children under 2 years old, and insurance coverage can be a problem. He noted, however, that various guidelines support their use even in the very young, “so I tell my physicians to fight for them ... If you need a steroid-sparing agent, push for it, because it may be the right thing for your patient,” he said.

He’s finding in his area that infected eczema often is resistant to clindamycin, which has been used heavily because of concerns about methicillin-resistant Staphylococcus aureus (MRSA). But it often will “respond to what we considered to be wimpier antibiotics in the past, such as cephalosporin ... So I’ll use cephalosporin or an extended-spectrum penicillin as my first-line agent, and then I’ll culture, depending on history, to see if I have to be concerned about methicillin resistance,” he said.

Be on the lookout for cutaneous herpes and show parents pictures of what it looks like so they recognize it and know to come in right away. It is a dangerous infection, but can be shut down quickly with oral acyclovir and similar agents, Dr. Eichenfield added.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – One of the most important steps in treating secondary infections in children with atopic dermatitis (AD) is bringing the eczema under control, according to Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at the University of California, San Diego.

It’s the breach in skin integrity that gives skin flora – most commonly Staphylococcus or Streptococcus – an opening for infection.

Dr. Eichenfield shared his treatment approach in a pearl-filled interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“Many times, anti-inflammatories are going to be the effective therapy,” whether topical steroids or systemic therapies. But with a secondary infection, systemic antibiotics are in order, too, but topical ones aren’t much use, he said.

Dr. Eichenfield gets a lot of questions about steroid-sparing options for very young children, since topical calcineurin inhibitors and the like aren’t approved in children under 2 years old, and insurance coverage can be a problem. He noted, however, that various guidelines support their use even in the very young, “so I tell my physicians to fight for them ... If you need a steroid-sparing agent, push for it, because it may be the right thing for your patient,” he said.

He’s finding in his area that infected eczema often is resistant to clindamycin, which has been used heavily because of concerns about methicillin-resistant Staphylococcus aureus (MRSA). But it often will “respond to what we considered to be wimpier antibiotics in the past, such as cephalosporin ... So I’ll use cephalosporin or an extended-spectrum penicillin as my first-line agent, and then I’ll culture, depending on history, to see if I have to be concerned about methicillin resistance,” he said.

Be on the lookout for cutaneous herpes and show parents pictures of what it looks like so they recognize it and know to come in right away. It is a dangerous infection, but can be shut down quickly with oral acyclovir and similar agents, Dr. Eichenfield added.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – One of the most important steps in treating secondary infections in children with atopic dermatitis (AD) is bringing the eczema under control, according to Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at the University of California, San Diego.

It’s the breach in skin integrity that gives skin flora – most commonly Staphylococcus or Streptococcus – an opening for infection.

Dr. Eichenfield shared his treatment approach in a pearl-filled interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“Many times, anti-inflammatories are going to be the effective therapy,” whether topical steroids or systemic therapies. But with a secondary infection, systemic antibiotics are in order, too, but topical ones aren’t much use, he said.

Dr. Eichenfield gets a lot of questions about steroid-sparing options for very young children, since topical calcineurin inhibitors and the like aren’t approved in children under 2 years old, and insurance coverage can be a problem. He noted, however, that various guidelines support their use even in the very young, “so I tell my physicians to fight for them ... If you need a steroid-sparing agent, push for it, because it may be the right thing for your patient,” he said.

He’s finding in his area that infected eczema often is resistant to clindamycin, which has been used heavily because of concerns about methicillin-resistant Staphylococcus aureus (MRSA). But it often will “respond to what we considered to be wimpier antibiotics in the past, such as cephalosporin ... So I’ll use cephalosporin or an extended-spectrum penicillin as my first-line agent, and then I’ll culture, depending on history, to see if I have to be concerned about methicillin resistance,” he said.

Be on the lookout for cutaneous herpes and show parents pictures of what it looks like so they recognize it and know to come in right away. It is a dangerous infection, but can be shut down quickly with oral acyclovir and similar agents, Dr. Eichenfield added.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.

A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.¹ Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.

Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.^2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”⁴ The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.

Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”⁵ Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.⁶

More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.⁷ The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.

The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.

References

1. https://www.youtube.com/watch?v=MpcUN6XvGmk.

2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.

3. Emerg (Tehran). 2014 Winter;2(1):36-9.

4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.

5. Psychol Med. 1971;1(3):191-6.

6. https://books.google.com/ngrams.

7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.

8. Am J Psychiatry. 2014 Apr;171(4):395-7.

9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.

10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.

11. “The ketamine connection.” BBC News. 2015 Jul 10.

12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.

13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.



*This article was updated 3/25/2019.

What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.

A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.¹ Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.

Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.^2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”⁴ The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.

Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”⁵ Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.⁶

More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.⁷ The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.

The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.

References

1. https://www.youtube.com/watch?v=MpcUN6XvGmk.

2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.

3. Emerg (Tehran). 2014 Winter;2(1):36-9.

4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.

5. Psychol Med. 1971;1(3):191-6.

6. https://books.google.com/ngrams.

7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.

8. Am J Psychiatry. 2014 Apr;171(4):395-7.

9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.

10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.

11. “The ketamine connection.” BBC News. 2015 Jul 10.

12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.

13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.



*This article was updated 3/25/2019.

What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.

A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.¹ Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.

Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.^2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”⁴ The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.

Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”⁵ Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.⁶

More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.⁷ The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.

The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.

References

1. https://www.youtube.com/watch?v=MpcUN6XvGmk.

2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.

3. Emerg (Tehran). 2014 Winter;2(1):36-9.

4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.

5. Psychol Med. 1971;1(3):191-6.

6. https://books.google.com/ngrams.

7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.

8. Am J Psychiatry. 2014 Apr;171(4):395-7.

9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.

10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.

11. “The ketamine connection.” BBC News. 2015 Jul 10.

12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.

13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.



*This article was updated 3/25/2019.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.

In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.

Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.

Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.

“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.

Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.

The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.

“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.

Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.

Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).

ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.

[email protected]

SOURCE: Ledermann J et al. SGO 2019, Abstract 4.

SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The first question is, What happens to the patient’s symptoms upon control of the hypertension?

“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.

An aortic valve area of less than 1.0 cm² is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?

“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm². You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.

These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.

“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.

Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.

This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.

The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm² or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”

Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.

“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.

Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.

“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.

One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).

This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.

When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.

“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
 

[email protected]

SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The first question is, What happens to the patient’s symptoms upon control of the hypertension?

“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.

An aortic valve area of less than 1.0 cm² is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?

“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm². You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.

These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.

“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.

Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.

This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.

The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm² or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”

Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.

“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.

Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.

“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.

One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).

This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.

When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.

“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
 

[email protected]

SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The first question is, What happens to the patient’s symptoms upon control of the hypertension?

“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.

An aortic valve area of less than 1.0 cm² is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?

“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm². You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.

These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.

“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.

Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.

This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.

The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm² or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”

Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.

“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.

Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.

“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.

One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).

This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.

When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.

“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
 

[email protected]

Sanctimonious, self-righteous, discharge saboteurs. These are just a few descriptors I’ve heard hospitalists use to describe my physical therapy (PT) colleagues.

These charged comments come mostly after a hospitalist reads therapy notes and encounters a contradiction to their chosen discharge location for a patient.

I recently met with hospitalists from four different hospitals. They echoed the frustrations of their physician colleagues across the country. The PTs they work with write “the patient requires 24-hour supervision and 3 hours of therapy a day,” or “the patient is unsafe to go home and needs continued therapy at an inpatient rehabilitation center.” The hospitalists in turn want to know “If I discharge the patient home am I liable if the patient falls or has some other negative outcome?” The frustration hospitalists experience is palpable and understandable as their attempts to support a home recovery are often contradicted.
 

Outside the four walls

The transition from fee-for-service to value-based care now calls upon hospitalists to be innovators in managing patients in alternative payment models, such as accountable care organizations, bundled payment programs, and Medicare Advantage plans. Each model looks to support a home recovery whenever possible and prevent readmissions.

Case managers for Medicare Advantage programs routinely review PT notes to inform hospital discharge disposition and post-acute authorization for skilled nursing facility (SNF) admissions and days in SNF. Hospitalists, working with care managers, can follow suit to succeed in alternative payment models. They have the advantage of in-person access to PT colleagues for elaboration and push-back as necessary. For hospitalists, working collaboratively with PTs is crucial to improving the value of care provided as patients transition beyond the four walls of the hospital.
 

The evolution of PT in acute care

Prior to diagnosis-related groups (DRGs), PTs were profit centers for hospitals – rehabilitation departments were well staffed and easily accommodated consults and requests for mobility.

With the advent of DRGs, physical therapy became a cost center, and rehabilitation staffs were reduced. PTs became overextended, were less available for consultations for mobilization, and patients suffered the deleterious effects of immobility. With reduced staffing and a rush to get patients out of the hospital, acute PT practice morphed into evaluating functional status and determining discharge destination.

Now, as members of an aligned health care team, PTs need to facilitate a safe home discharge whenever possible and determine what skilled services a patient needs post-acute stay, not where they should receive them.
 

Discharge disposition and longitudinal recovery

PTs, as experts in function, have a series of “special tests” at their disposal beyond pain, range of motion, and strength assessments. These include: Activity Measure for Post-Acute Care (AM-PAC) or “6-Clicks” Mobility Score, Timed Up and Go, Six-Minute Walk Test, Tinetti, Berg Balance Scale, Modified Barthel Index, Five Times Chair Rise, and Thirty-Second Chair Rise. These are all objective measures of function that can be used to inform discharge disposition and guide longitudinal recovery.

To elaborate on one tool, the 6-Clicks Mobility Score is a validated test that allows PTs to assess basic mobility.^1,2 It rates six functional tasks (hence 6 clicks) that include: turning over in bed, moving from lying to sitting, moving to/from bed to chair, transitioning from sitting to standing from a chair, walking in a hospital room, and climbing three to five steps. These functional tasks are scored based on the amount of assistance needed. The scores, in turn, have been shown to support discharge destination planning.¹ In addition to informing discharge destination decisions, hospitalists and the rest of the health care team can use 6-Clicks to estimate prolonged hospital stays, readmissions, and emergency department (ED) visits.³

Of course, discharge disposition is influenced by many factors in addition to functional status. Hospitalists are the obvious choice to lead the health care team in interpreting relevant data and test results, and to communicate these results to patients and caregivers so together they can decide the most appropriate discharge destination.

I envision a conversation between a fully informed hospitalist and a patient as follows: “Based on your past history, your living situation, all of your test results including labs, x-rays and the functional tests performed by your PT, your potential for a full recovery is good. You have a moderate decline in function with a high likelihood of returning home in the next 7-10 days. I recommend you go to a SNF for high-intensity rehabilitation for 7 days and that the SNF order PT and OT twice a day and walks with nursing every evening.”

This fully informed conversation can only take place if hospitalists are provided clear, concise documentation, including results of objective functional testing, by their physical therapy colleagues.

In conclusion, PTs working in the acute setting need to use validated tests to objectively assess function and educate their hospitalist colleagues on the meaning of these tests. Hospitalists in turn can incorporate these assessments into a discussion of discharge disposition and longitudinal recovery with patients. In this way, hospitalists and physical therapists can work together to achieve patient-centered, high-value care during and following a hospitalization.
 

Ms. Tammany is SVP of clinical strategy & innovation for Remedy Partners, Norwalk, Conn.

References

1. Jette DU et al. AM-PAC “6-Clicks” functional assessment scores predict acute care hospital discharge destination. Phys Ther. 2014 Sep;94(9):1252-61.

2. Jette DU et al. Validity of the AM-PAC “6-Clicks” inpatient daily activity and basic mobility short forms. Phys Ther. 2014 Mar;94(3):379-91.

3. Menendez ME et al. Does “6-Clicks” Day 1 Postoperative Mobility Score Predict Discharge Disposition After Total Hip and Knee Arthroplasties?” J Arthroplasty. 2016 Sep;31(9):1916-20.

Sanctimonious, self-righteous, discharge saboteurs. These are just a few descriptors I’ve heard hospitalists use to describe my physical therapy (PT) colleagues.

These charged comments come mostly after a hospitalist reads therapy notes and encounters a contradiction to their chosen discharge location for a patient.

I recently met with hospitalists from four different hospitals. They echoed the frustrations of their physician colleagues across the country. The PTs they work with write “the patient requires 24-hour supervision and 3 hours of therapy a day,” or “the patient is unsafe to go home and needs continued therapy at an inpatient rehabilitation center.” The hospitalists in turn want to know “If I discharge the patient home am I liable if the patient falls or has some other negative outcome?” The frustration hospitalists experience is palpable and understandable as their attempts to support a home recovery are often contradicted.
 

Outside the four walls

The transition from fee-for-service to value-based care now calls upon hospitalists to be innovators in managing patients in alternative payment models, such as accountable care organizations, bundled payment programs, and Medicare Advantage plans. Each model looks to support a home recovery whenever possible and prevent readmissions.

Case managers for Medicare Advantage programs routinely review PT notes to inform hospital discharge disposition and post-acute authorization for skilled nursing facility (SNF) admissions and days in SNF. Hospitalists, working with care managers, can follow suit to succeed in alternative payment models. They have the advantage of in-person access to PT colleagues for elaboration and push-back as necessary. For hospitalists, working collaboratively with PTs is crucial to improving the value of care provided as patients transition beyond the four walls of the hospital.
 

The evolution of PT in acute care

Prior to diagnosis-related groups (DRGs), PTs were profit centers for hospitals – rehabilitation departments were well staffed and easily accommodated consults and requests for mobility.

With the advent of DRGs, physical therapy became a cost center, and rehabilitation staffs were reduced. PTs became overextended, were less available for consultations for mobilization, and patients suffered the deleterious effects of immobility. With reduced staffing and a rush to get patients out of the hospital, acute PT practice morphed into evaluating functional status and determining discharge destination.

Now, as members of an aligned health care team, PTs need to facilitate a safe home discharge whenever possible and determine what skilled services a patient needs post-acute stay, not where they should receive them.
 

Discharge disposition and longitudinal recovery

PTs, as experts in function, have a series of “special tests” at their disposal beyond pain, range of motion, and strength assessments. These include: Activity Measure for Post-Acute Care (AM-PAC) or “6-Clicks” Mobility Score, Timed Up and Go, Six-Minute Walk Test, Tinetti, Berg Balance Scale, Modified Barthel Index, Five Times Chair Rise, and Thirty-Second Chair Rise. These are all objective measures of function that can be used to inform discharge disposition and guide longitudinal recovery.

To elaborate on one tool, the 6-Clicks Mobility Score is a validated test that allows PTs to assess basic mobility.^1,2 It rates six functional tasks (hence 6 clicks) that include: turning over in bed, moving from lying to sitting, moving to/from bed to chair, transitioning from sitting to standing from a chair, walking in a hospital room, and climbing three to five steps. These functional tasks are scored based on the amount of assistance needed. The scores, in turn, have been shown to support discharge destination planning.¹ In addition to informing discharge destination decisions, hospitalists and the rest of the health care team can use 6-Clicks to estimate prolonged hospital stays, readmissions, and emergency department (ED) visits.³

Of course, discharge disposition is influenced by many factors in addition to functional status. Hospitalists are the obvious choice to lead the health care team in interpreting relevant data and test results, and to communicate these results to patients and caregivers so together they can decide the most appropriate discharge destination.

I envision a conversation between a fully informed hospitalist and a patient as follows: “Based on your past history, your living situation, all of your test results including labs, x-rays and the functional tests performed by your PT, your potential for a full recovery is good. You have a moderate decline in function with a high likelihood of returning home in the next 7-10 days. I recommend you go to a SNF for high-intensity rehabilitation for 7 days and that the SNF order PT and OT twice a day and walks with nursing every evening.”

This fully informed conversation can only take place if hospitalists are provided clear, concise documentation, including results of objective functional testing, by their physical therapy colleagues.

In conclusion, PTs working in the acute setting need to use validated tests to objectively assess function and educate their hospitalist colleagues on the meaning of these tests. Hospitalists in turn can incorporate these assessments into a discussion of discharge disposition and longitudinal recovery with patients. In this way, hospitalists and physical therapists can work together to achieve patient-centered, high-value care during and following a hospitalization.
 

Ms. Tammany is SVP of clinical strategy & innovation for Remedy Partners, Norwalk, Conn.

References

1. Jette DU et al. AM-PAC “6-Clicks” functional assessment scores predict acute care hospital discharge destination. Phys Ther. 2014 Sep;94(9):1252-61.

2. Jette DU et al. Validity of the AM-PAC “6-Clicks” inpatient daily activity and basic mobility short forms. Phys Ther. 2014 Mar;94(3):379-91.

3. Menendez ME et al. Does “6-Clicks” Day 1 Postoperative Mobility Score Predict Discharge Disposition After Total Hip and Knee Arthroplasties?” J Arthroplasty. 2016 Sep;31(9):1916-20.

Sanctimonious, self-righteous, discharge saboteurs. These are just a few descriptors I’ve heard hospitalists use to describe my physical therapy (PT) colleagues.

These charged comments come mostly after a hospitalist reads therapy notes and encounters a contradiction to their chosen discharge location for a patient.

I recently met with hospitalists from four different hospitals. They echoed the frustrations of their physician colleagues across the country. The PTs they work with write “the patient requires 24-hour supervision and 3 hours of therapy a day,” or “the patient is unsafe to go home and needs continued therapy at an inpatient rehabilitation center.” The hospitalists in turn want to know “If I discharge the patient home am I liable if the patient falls or has some other negative outcome?” The frustration hospitalists experience is palpable and understandable as their attempts to support a home recovery are often contradicted.
 

Outside the four walls

The transition from fee-for-service to value-based care now calls upon hospitalists to be innovators in managing patients in alternative payment models, such as accountable care organizations, bundled payment programs, and Medicare Advantage plans. Each model looks to support a home recovery whenever possible and prevent readmissions.

Case managers for Medicare Advantage programs routinely review PT notes to inform hospital discharge disposition and post-acute authorization for skilled nursing facility (SNF) admissions and days in SNF. Hospitalists, working with care managers, can follow suit to succeed in alternative payment models. They have the advantage of in-person access to PT colleagues for elaboration and push-back as necessary. For hospitalists, working collaboratively with PTs is crucial to improving the value of care provided as patients transition beyond the four walls of the hospital.
 

The evolution of PT in acute care

Prior to diagnosis-related groups (DRGs), PTs were profit centers for hospitals – rehabilitation departments were well staffed and easily accommodated consults and requests for mobility.

With the advent of DRGs, physical therapy became a cost center, and rehabilitation staffs were reduced. PTs became overextended, were less available for consultations for mobilization, and patients suffered the deleterious effects of immobility. With reduced staffing and a rush to get patients out of the hospital, acute PT practice morphed into evaluating functional status and determining discharge destination.

Now, as members of an aligned health care team, PTs need to facilitate a safe home discharge whenever possible and determine what skilled services a patient needs post-acute stay, not where they should receive them.
 

Discharge disposition and longitudinal recovery

PTs, as experts in function, have a series of “special tests” at their disposal beyond pain, range of motion, and strength assessments. These include: Activity Measure for Post-Acute Care (AM-PAC) or “6-Clicks” Mobility Score, Timed Up and Go, Six-Minute Walk Test, Tinetti, Berg Balance Scale, Modified Barthel Index, Five Times Chair Rise, and Thirty-Second Chair Rise. These are all objective measures of function that can be used to inform discharge disposition and guide longitudinal recovery.

To elaborate on one tool, the 6-Clicks Mobility Score is a validated test that allows PTs to assess basic mobility.^1,2 It rates six functional tasks (hence 6 clicks) that include: turning over in bed, moving from lying to sitting, moving to/from bed to chair, transitioning from sitting to standing from a chair, walking in a hospital room, and climbing three to five steps. These functional tasks are scored based on the amount of assistance needed. The scores, in turn, have been shown to support discharge destination planning.¹ In addition to informing discharge destination decisions, hospitalists and the rest of the health care team can use 6-Clicks to estimate prolonged hospital stays, readmissions, and emergency department (ED) visits.³

Of course, discharge disposition is influenced by many factors in addition to functional status. Hospitalists are the obvious choice to lead the health care team in interpreting relevant data and test results, and to communicate these results to patients and caregivers so together they can decide the most appropriate discharge destination.

I envision a conversation between a fully informed hospitalist and a patient as follows: “Based on your past history, your living situation, all of your test results including labs, x-rays and the functional tests performed by your PT, your potential for a full recovery is good. You have a moderate decline in function with a high likelihood of returning home in the next 7-10 days. I recommend you go to a SNF for high-intensity rehabilitation for 7 days and that the SNF order PT and OT twice a day and walks with nursing every evening.”

This fully informed conversation can only take place if hospitalists are provided clear, concise documentation, including results of objective functional testing, by their physical therapy colleagues.

In conclusion, PTs working in the acute setting need to use validated tests to objectively assess function and educate their hospitalist colleagues on the meaning of these tests. Hospitalists in turn can incorporate these assessments into a discussion of discharge disposition and longitudinal recovery with patients. In this way, hospitalists and physical therapists can work together to achieve patient-centered, high-value care during and following a hospitalization.
 

Ms. Tammany is SVP of clinical strategy & innovation for Remedy Partners, Norwalk, Conn.

References

1. Jette DU et al. AM-PAC “6-Clicks” functional assessment scores predict acute care hospital discharge destination. Phys Ther. 2014 Sep;94(9):1252-61.

2. Jette DU et al. Validity of the AM-PAC “6-Clicks” inpatient daily activity and basic mobility short forms. Phys Ther. 2014 Mar;94(3):379-91.

3. Menendez ME et al. Does “6-Clicks” Day 1 Postoperative Mobility Score Predict Discharge Disposition After Total Hip and Knee Arthroplasties?” J Arthroplasty. 2016 Sep;31(9):1916-20.

NEW ORLEANS – Abstinence from alcohol on the part of moderate drinkers with atrial fibrillation resulted in clinically meaningful improvement in their arrhythmia in the randomized controlled Alcohol-AF trial, Aleksandr Voskoboinik, MBBS, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

The benefits of abstinence included significant reductions in the AFib recurrence rate, total AFib burden, and symptom severity. And the payoff extended beyond the arrhythmia: The abstinent group also averaged a 12–mm Hg drop in systolic blood pressure and dropped 3 kg of body weight over the course of the 6-month trial, added Dr. Voskoboinik, a cardiologist at the Baker Heart & Diabetes Institute at the University of Melbourne.

“We would conclude that significant reduction in alcohol intake should be considered as part of the lifestyle intervention in moderate drinkers with AFib,” he said.

Some physicians already advise alcohol abstinence for moderate drinkers with AFib, but until now such recommendations were not evidence based. Instead, the guidance was based on extrapolation from the well-established harmful effects of heavy drinking and binge drinking on AFib as well as epidemiologic studies.

“We wanted to provide some evidence base for physicians to say, ‘If I have motivated patients, here’s what’s potentially achievable,’” he explained.

The key word here is “motivated.” Conducting the Alcohol-AF trial made clear that many moderate drinkers with AFib enjoy their beverages more than they hate having their arrhythmia. Indeed, out of 697 moderate-drinking patients with paroxysmal or persistent AFib who were deemed good candidates and were approached about study participation, more than 500 were excluded because they were flat out unwilling to consider abstinence. After Dr. Voskoboinik and his coinvestigators shortened the planned trial duration from 12 months to 6 because so many recruits were unwilling to abstain for a full year, 140 of the initial 697 patients were randomized to abstinence or continuation of their usual consumption. Thirty percent of them had previously undergone AFib ablation.

Symptom severity, a secondary endpoint, showed an impressive between-group difference at follow-up. Ten percent of patients in the abstinence group had moderate or severe symptoms at follow-up as assessed via the European Heart Rhythm Association score of atrial fibrillation, compared to 32% of controls, for an absolute 22% difference. And 90% of the abstinence group had no or mild symptoms, as did 68% of controls. Nine percent of the abstinence group had an AFib-related hospitalization, as did 20% of controls.

Cardiac MRI, performed in all subjects, showed that the abstinence group experienced a significant reduction in left atrial area, from 29.5 cm² at baseline to 27.1 cm² at follow-up. They also experienced significant improvement in left atrial mechanical function, with their left atrial emptying fraction climbing from 42% to 50%.

The 3-kg weight loss from a baseline of 90 kg in the abstinent group represented a 0.7 kg/m² reduction in body mass index.

In terms of the likely mechanism of benefit of alcohol abstinence in moderate drinkers, Dr. Voskoboinik noted that he and his colleagues recently demonstrated that regular moderate alcohol consumption, but not mild intake, is associated with potentially explanatory atrial electrical and structural changes, including conduction slowing, lower global bipolar atrial voltage, and an increase in complex atrial potentials (Heart Rhythm. 2019 Feb;16[2]:251-9).

Alcohol has been shown to be linked with AFib through multiple mechanisms. Alcohol has adverse effects on the atrial substrate, including promotion of left atrial remodeling, dilation, and fibrosis via oxidative stress, and alcohol has a contributory role in hypertension and obstructive sleep apnea. Alcohol can act as an acute trigger of AFib through binge drinking – the holiday heart syndrome – which causes autonomic changes, electrolyte abnormalities, and electrophysiologic effects, he continued.

Epidemiologic evidence in support of the notion that moderate drinking increases the risk of AFib includes a Swedish meta-analysis of seven prospective studies comprising 12,554 patients with AFib. The researchers concluded that the relative risk of AFib rose by about 8% with each drink per day, compared with the risk of a reference group composed of current drinkers at a rate of less than one drink per week (J Am Coll Cardiol. 2014 Jul 22;64[3]:281-9).

Although discussants were wowed by the 61% complete abstinence rate in the trial, Dr. Voskoboinik cautioned that the study participants were a highly motivated subset of the universe of moderate drinkers with AFib. And even so, “It was an incredibly challenging study to run,” he said.

“I think lifestyle change is a challenge, and with alcohol particularly so, because alcohol is so ubiquitous in our society. I think the important key message for us as physicians is to take an alcohol history and have a discussion with the patient. And we now have some data to show them. But at the end of the day, it’s up to the patient in conjunction with the physician,” he observed.

Discussant Annabelle S. Volgman, MD, noted that 85% of study participants were men, and because of important differences in AFib between men and women, she doesn’t consider the findings applicable to women.

Bruce Jancin/MDedge News

“You need to redo the study in women,” advised Dr. Volgman, professor of medicine at Rush University, Chicago, and director of the Rush Heart Center for Women.

She suggested that an interventional trial such as this one is a great opportunity to utilize wearable device technology, such as the Apple Watch, which can detect irregular pulse rhythms as demonstrated in the Apple Heart Study. This technology is especially popular with younger individuals.

“A lot of young men and women drink a lot of alcohol,” Dr. Volgman noted.

“That’s a great idea. It gets around a problem with AliveCor, which can miss episodes while you’re sleeping,” Dr. Voskoboinik replied.

He reported having no financial conflicts regarding the investigator-initiated and -funded Alcohol-AF trial.

[email protected]

SOURCE: Voskoboinik A. ACC 19, Session 413-08.

NEW ORLEANS – Abstinence from alcohol on the part of moderate drinkers with atrial fibrillation resulted in clinically meaningful improvement in their arrhythmia in the randomized controlled Alcohol-AF trial, Aleksandr Voskoboinik, MBBS, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

The benefits of abstinence included significant reductions in the AFib recurrence rate, total AFib burden, and symptom severity. And the payoff extended beyond the arrhythmia: The abstinent group also averaged a 12–mm Hg drop in systolic blood pressure and dropped 3 kg of body weight over the course of the 6-month trial, added Dr. Voskoboinik, a cardiologist at the Baker Heart & Diabetes Institute at the University of Melbourne.

“We would conclude that significant reduction in alcohol intake should be considered as part of the lifestyle intervention in moderate drinkers with AFib,” he said.

Some physicians already advise alcohol abstinence for moderate drinkers with AFib, but until now such recommendations were not evidence based. Instead, the guidance was based on extrapolation from the well-established harmful effects of heavy drinking and binge drinking on AFib as well as epidemiologic studies.

“We wanted to provide some evidence base for physicians to say, ‘If I have motivated patients, here’s what’s potentially achievable,’” he explained.

The key word here is “motivated.” Conducting the Alcohol-AF trial made clear that many moderate drinkers with AFib enjoy their beverages more than they hate having their arrhythmia. Indeed, out of 697 moderate-drinking patients with paroxysmal or persistent AFib who were deemed good candidates and were approached about study participation, more than 500 were excluded because they were flat out unwilling to consider abstinence. After Dr. Voskoboinik and his coinvestigators shortened the planned trial duration from 12 months to 6 because so many recruits were unwilling to abstain for a full year, 140 of the initial 697 patients were randomized to abstinence or continuation of their usual consumption. Thirty percent of them had previously undergone AFib ablation.

Symptom severity, a secondary endpoint, showed an impressive between-group difference at follow-up. Ten percent of patients in the abstinence group had moderate or severe symptoms at follow-up as assessed via the European Heart Rhythm Association score of atrial fibrillation, compared to 32% of controls, for an absolute 22% difference. And 90% of the abstinence group had no or mild symptoms, as did 68% of controls. Nine percent of the abstinence group had an AFib-related hospitalization, as did 20% of controls.

Cardiac MRI, performed in all subjects, showed that the abstinence group experienced a significant reduction in left atrial area, from 29.5 cm² at baseline to 27.1 cm² at follow-up. They also experienced significant improvement in left atrial mechanical function, with their left atrial emptying fraction climbing from 42% to 50%.

The 3-kg weight loss from a baseline of 90 kg in the abstinent group represented a 0.7 kg/m² reduction in body mass index.

In terms of the likely mechanism of benefit of alcohol abstinence in moderate drinkers, Dr. Voskoboinik noted that he and his colleagues recently demonstrated that regular moderate alcohol consumption, but not mild intake, is associated with potentially explanatory atrial electrical and structural changes, including conduction slowing, lower global bipolar atrial voltage, and an increase in complex atrial potentials (Heart Rhythm. 2019 Feb;16[2]:251-9).

Alcohol has been shown to be linked with AFib through multiple mechanisms. Alcohol has adverse effects on the atrial substrate, including promotion of left atrial remodeling, dilation, and fibrosis via oxidative stress, and alcohol has a contributory role in hypertension and obstructive sleep apnea. Alcohol can act as an acute trigger of AFib through binge drinking – the holiday heart syndrome – which causes autonomic changes, electrolyte abnormalities, and electrophysiologic effects, he continued.

Epidemiologic evidence in support of the notion that moderate drinking increases the risk of AFib includes a Swedish meta-analysis of seven prospective studies comprising 12,554 patients with AFib. The researchers concluded that the relative risk of AFib rose by about 8% with each drink per day, compared with the risk of a reference group composed of current drinkers at a rate of less than one drink per week (J Am Coll Cardiol. 2014 Jul 22;64[3]:281-9).

Although discussants were wowed by the 61% complete abstinence rate in the trial, Dr. Voskoboinik cautioned that the study participants were a highly motivated subset of the universe of moderate drinkers with AFib. And even so, “It was an incredibly challenging study to run,” he said.

“I think lifestyle change is a challenge, and with alcohol particularly so, because alcohol is so ubiquitous in our society. I think the important key message for us as physicians is to take an alcohol history and have a discussion with the patient. And we now have some data to show them. But at the end of the day, it’s up to the patient in conjunction with the physician,” he observed.

Discussant Annabelle S. Volgman, MD, noted that 85% of study participants were men, and because of important differences in AFib between men and women, she doesn’t consider the findings applicable to women.

Bruce Jancin/MDedge News

“You need to redo the study in women,” advised Dr. Volgman, professor of medicine at Rush University, Chicago, and director of the Rush Heart Center for Women.

She suggested that an interventional trial such as this one is a great opportunity to utilize wearable device technology, such as the Apple Watch, which can detect irregular pulse rhythms as demonstrated in the Apple Heart Study. This technology is especially popular with younger individuals.

“A lot of young men and women drink a lot of alcohol,” Dr. Volgman noted.

“That’s a great idea. It gets around a problem with AliveCor, which can miss episodes while you’re sleeping,” Dr. Voskoboinik replied.

He reported having no financial conflicts regarding the investigator-initiated and -funded Alcohol-AF trial.

[email protected]

SOURCE: Voskoboinik A. ACC 19, Session 413-08.

NEW ORLEANS – Abstinence from alcohol on the part of moderate drinkers with atrial fibrillation resulted in clinically meaningful improvement in their arrhythmia in the randomized controlled Alcohol-AF trial, Aleksandr Voskoboinik, MBBS, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

The benefits of abstinence included significant reductions in the AFib recurrence rate, total AFib burden, and symptom severity. And the payoff extended beyond the arrhythmia: The abstinent group also averaged a 12–mm Hg drop in systolic blood pressure and dropped 3 kg of body weight over the course of the 6-month trial, added Dr. Voskoboinik, a cardiologist at the Baker Heart & Diabetes Institute at the University of Melbourne.

“We would conclude that significant reduction in alcohol intake should be considered as part of the lifestyle intervention in moderate drinkers with AFib,” he said.

Some physicians already advise alcohol abstinence for moderate drinkers with AFib, but until now such recommendations were not evidence based. Instead, the guidance was based on extrapolation from the well-established harmful effects of heavy drinking and binge drinking on AFib as well as epidemiologic studies.

“We wanted to provide some evidence base for physicians to say, ‘If I have motivated patients, here’s what’s potentially achievable,’” he explained.

The key word here is “motivated.” Conducting the Alcohol-AF trial made clear that many moderate drinkers with AFib enjoy their beverages more than they hate having their arrhythmia. Indeed, out of 697 moderate-drinking patients with paroxysmal or persistent AFib who were deemed good candidates and were approached about study participation, more than 500 were excluded because they were flat out unwilling to consider abstinence. After Dr. Voskoboinik and his coinvestigators shortened the planned trial duration from 12 months to 6 because so many recruits were unwilling to abstain for a full year, 140 of the initial 697 patients were randomized to abstinence or continuation of their usual consumption. Thirty percent of them had previously undergone AFib ablation.

Symptom severity, a secondary endpoint, showed an impressive between-group difference at follow-up. Ten percent of patients in the abstinence group had moderate or severe symptoms at follow-up as assessed via the European Heart Rhythm Association score of atrial fibrillation, compared to 32% of controls, for an absolute 22% difference. And 90% of the abstinence group had no or mild symptoms, as did 68% of controls. Nine percent of the abstinence group had an AFib-related hospitalization, as did 20% of controls.

Cardiac MRI, performed in all subjects, showed that the abstinence group experienced a significant reduction in left atrial area, from 29.5 cm² at baseline to 27.1 cm² at follow-up. They also experienced significant improvement in left atrial mechanical function, with their left atrial emptying fraction climbing from 42% to 50%.

The 3-kg weight loss from a baseline of 90 kg in the abstinent group represented a 0.7 kg/m² reduction in body mass index.

In terms of the likely mechanism of benefit of alcohol abstinence in moderate drinkers, Dr. Voskoboinik noted that he and his colleagues recently demonstrated that regular moderate alcohol consumption, but not mild intake, is associated with potentially explanatory atrial electrical and structural changes, including conduction slowing, lower global bipolar atrial voltage, and an increase in complex atrial potentials (Heart Rhythm. 2019 Feb;16[2]:251-9).

Alcohol has been shown to be linked with AFib through multiple mechanisms. Alcohol has adverse effects on the atrial substrate, including promotion of left atrial remodeling, dilation, and fibrosis via oxidative stress, and alcohol has a contributory role in hypertension and obstructive sleep apnea. Alcohol can act as an acute trigger of AFib through binge drinking – the holiday heart syndrome – which causes autonomic changes, electrolyte abnormalities, and electrophysiologic effects, he continued.

Epidemiologic evidence in support of the notion that moderate drinking increases the risk of AFib includes a Swedish meta-analysis of seven prospective studies comprising 12,554 patients with AFib. The researchers concluded that the relative risk of AFib rose by about 8% with each drink per day, compared with the risk of a reference group composed of current drinkers at a rate of less than one drink per week (J Am Coll Cardiol. 2014 Jul 22;64[3]:281-9).

Although discussants were wowed by the 61% complete abstinence rate in the trial, Dr. Voskoboinik cautioned that the study participants were a highly motivated subset of the universe of moderate drinkers with AFib. And even so, “It was an incredibly challenging study to run,” he said.

“I think lifestyle change is a challenge, and with alcohol particularly so, because alcohol is so ubiquitous in our society. I think the important key message for us as physicians is to take an alcohol history and have a discussion with the patient. And we now have some data to show them. But at the end of the day, it’s up to the patient in conjunction with the physician,” he observed.

Discussant Annabelle S. Volgman, MD, noted that 85% of study participants were men, and because of important differences in AFib between men and women, she doesn’t consider the findings applicable to women.

Bruce Jancin/MDedge News

“You need to redo the study in women,” advised Dr. Volgman, professor of medicine at Rush University, Chicago, and director of the Rush Heart Center for Women.

She suggested that an interventional trial such as this one is a great opportunity to utilize wearable device technology, such as the Apple Watch, which can detect irregular pulse rhythms as demonstrated in the Apple Heart Study. This technology is especially popular with younger individuals.

“A lot of young men and women drink a lot of alcohol,” Dr. Volgman noted.

“That’s a great idea. It gets around a problem with AliveCor, which can miss episodes while you’re sleeping,” Dr. Voskoboinik replied.

He reported having no financial conflicts regarding the investigator-initiated and -funded Alcohol-AF trial.

[email protected]

SOURCE: Voskoboinik A. ACC 19, Session 413-08.

Biogen and Eisai have announced that they are discontinuing the ENGAGE and EMERGE trials, which were designed to test the efficacy and safety of aducanumab in patients with mild cognitive impairment caused by Alzheimer’s disease and mild Alzheimer’s disease dementia.

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trials were canceled not because of safety concerns but because of a futility analysis conducted by an independent data monitoring committee that indicated the drug would not meet the trials’ primary endpoint, which was the slowing of cognitive and functional impairment as measured by changes in Clinical Dementia Rating–Sum of Boxes score, compared with placebo.

In addition to ENGAGE and EMERGE, the phase 2 EVOLVE safety study and the long-term extension of the phase 1b PRIME study have also been canceled. Data from the ENGAGE and EMERGE trials will be presented at future medical meetings.

Aducanumab is a human monoclonal antibody derived from B cells collected from healthy elderly subjects with no cognitive decline or those with unusually slow cognitive decline through Neurimmune’s technology platform called Reverse Translational Medicine. It was granted Fast Track designation by the Food and Drug Administration.

“This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience. We are incredibly grateful to all the Alzheimer’s disease patients, their families, and the investigators who participated in the trials and contributed greatly to this research,” Michel Vounatsos, CEO at Biogen, said in a press release.

[email protected]

Biogen and Eisai have announced that they are discontinuing the ENGAGE and EMERGE trials, which were designed to test the efficacy and safety of aducanumab in patients with mild cognitive impairment caused by Alzheimer’s disease and mild Alzheimer’s disease dementia.

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trials were canceled not because of safety concerns but because of a futility analysis conducted by an independent data monitoring committee that indicated the drug would not meet the trials’ primary endpoint, which was the slowing of cognitive and functional impairment as measured by changes in Clinical Dementia Rating–Sum of Boxes score, compared with placebo.

In addition to ENGAGE and EMERGE, the phase 2 EVOLVE safety study and the long-term extension of the phase 1b PRIME study have also been canceled. Data from the ENGAGE and EMERGE trials will be presented at future medical meetings.

Aducanumab is a human monoclonal antibody derived from B cells collected from healthy elderly subjects with no cognitive decline or those with unusually slow cognitive decline through Neurimmune’s technology platform called Reverse Translational Medicine. It was granted Fast Track designation by the Food and Drug Administration.

“This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience. We are incredibly grateful to all the Alzheimer’s disease patients, their families, and the investigators who participated in the trials and contributed greatly to this research,” Michel Vounatsos, CEO at Biogen, said in a press release.

[email protected]

Biogen and Eisai have announced that they are discontinuing the ENGAGE and EMERGE trials, which were designed to test the efficacy and safety of aducanumab in patients with mild cognitive impairment caused by Alzheimer’s disease and mild Alzheimer’s disease dementia.

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trials were canceled not because of safety concerns but because of a futility analysis conducted by an independent data monitoring committee that indicated the drug would not meet the trials’ primary endpoint, which was the slowing of cognitive and functional impairment as measured by changes in Clinical Dementia Rating–Sum of Boxes score, compared with placebo.

In addition to ENGAGE and EMERGE, the phase 2 EVOLVE safety study and the long-term extension of the phase 1b PRIME study have also been canceled. Data from the ENGAGE and EMERGE trials will be presented at future medical meetings.

Aducanumab is a human monoclonal antibody derived from B cells collected from healthy elderly subjects with no cognitive decline or those with unusually slow cognitive decline through Neurimmune’s technology platform called Reverse Translational Medicine. It was granted Fast Track designation by the Food and Drug Administration.

“This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience. We are incredibly grateful to all the Alzheimer’s disease patients, their families, and the investigators who participated in the trials and contributed greatly to this research,” Michel Vounatsos, CEO at Biogen, said in a press release.

[email protected]

Planning a wedding doesn’t just involve decisions on venues, vows, guests, food, and décor, but also on the betrothed couple’s appearance. Memories and photographs from this day last a lifetime, so it is understandable that people may want to and feel pressured to look their best on this important day – which along with the pressures of planning a wedding, can lead to unnecessary stress, increased cortisol, and unexpected acne and other skin issues.

llhedgehogll/Thinkstock

Because of a complete absence of wedding skin recommendations in the dermatology literature, Winklemann R et al. recently published a paper titled “Wedding Dermatology: A proposed timeline to optimize skin clearance and the avoidance of a true dermatologic emergency” (SKIN The Journal of Cutaneous Medicine 2019 Mar;3[2]:159-60). He focused on acne, using the American Academy of Dermatology acne treatment guidelines and expert opinion, they point out that other than intralesional corticosteroids (which take 0-14 days to have an effect), the majority of acne treatments require at least 3-12 months to achieve clearance or improvement.

This proposed treatment timeline makes sense given that skin cell turnover on the face takes about 6-8 weeks; therefore, it may take that long for acne lesions to resolve or for treatment to have an effect.

Besides acne treatment, cosmetic treatments also have varying healing times and may require multiple sessions with time in between treatments for optimal results. For instance, treatment of photoaging with intense pulsed light or nonablative fractionated resurfacing may require three to six treatments, typically spaced 1 month apart.

Botulinum toxin treatments may take up to 2 weeks to kick in fully, then last 3-4 months. While the lead time for botulinum toxin to kick in is relatively short, I advise people not to get their first botulinum toxin 2 weeks before their wedding. Sometimes, having this treatment 4-6 weeks prior to the wedding date provides enough time for botulinum toxin to kick in – and to start wearing off to the point that the patient has the desired cosmetic effect, but still has some movement for the desired emotional facial expressions on the wedding day. Some patients also may require touch-ups, optimally at the 2-week window, once the botulinum toxin effect has fully kicked in.

With any injectable, there may be bruising and swelling that can take a week or so to heal, even when the bruises are treated with pulse dye laser used to make bruises resolve more quickly. Even a facial may result in blemishes that take a few days to 1-2 weeks to heal, especially with extractions. As such, a facial, especially a hydrafacial, may be beneficial before one’s wedding, but I would recommend having them done at least once or twice to assess an individual’s recovery time (if any) prior to the actual wedding date.

Treatment needs will vary considerably depending on the patient’s baseline skin health. As dermatologists, our patients depend greatly on us to help them look and feel their best, especially during a time when they are about to embark on a new journey like marriage. Patients need to be given realistic treatment options and time frames to achieve their goals. Whether the goal is treating acne or acne scars, starting or fine-tuning cosmetic treatments, or deciding on a skin-care regimen, the bottom line is making an appointment with the dermatologist early – 6-12 months in advance, if possible – to figure out the right plan.
 

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
 

Planning a wedding doesn’t just involve decisions on venues, vows, guests, food, and décor, but also on the betrothed couple’s appearance. Memories and photographs from this day last a lifetime, so it is understandable that people may want to and feel pressured to look their best on this important day – which along with the pressures of planning a wedding, can lead to unnecessary stress, increased cortisol, and unexpected acne and other skin issues.

llhedgehogll/Thinkstock

Because of a complete absence of wedding skin recommendations in the dermatology literature, Winklemann R et al. recently published a paper titled “Wedding Dermatology: A proposed timeline to optimize skin clearance and the avoidance of a true dermatologic emergency” (SKIN The Journal of Cutaneous Medicine 2019 Mar;3[2]:159-60). He focused on acne, using the American Academy of Dermatology acne treatment guidelines and expert opinion, they point out that other than intralesional corticosteroids (which take 0-14 days to have an effect), the majority of acne treatments require at least 3-12 months to achieve clearance or improvement.

This proposed treatment timeline makes sense given that skin cell turnover on the face takes about 6-8 weeks; therefore, it may take that long for acne lesions to resolve or for treatment to have an effect.

Besides acne treatment, cosmetic treatments also have varying healing times and may require multiple sessions with time in between treatments for optimal results. For instance, treatment of photoaging with intense pulsed light or nonablative fractionated resurfacing may require three to six treatments, typically spaced 1 month apart.

Botulinum toxin treatments may take up to 2 weeks to kick in fully, then last 3-4 months. While the lead time for botulinum toxin to kick in is relatively short, I advise people not to get their first botulinum toxin 2 weeks before their wedding. Sometimes, having this treatment 4-6 weeks prior to the wedding date provides enough time for botulinum toxin to kick in – and to start wearing off to the point that the patient has the desired cosmetic effect, but still has some movement for the desired emotional facial expressions on the wedding day. Some patients also may require touch-ups, optimally at the 2-week window, once the botulinum toxin effect has fully kicked in.

With any injectable, there may be bruising and swelling that can take a week or so to heal, even when the bruises are treated with pulse dye laser used to make bruises resolve more quickly. Even a facial may result in blemishes that take a few days to 1-2 weeks to heal, especially with extractions. As such, a facial, especially a hydrafacial, may be beneficial before one’s wedding, but I would recommend having them done at least once or twice to assess an individual’s recovery time (if any) prior to the actual wedding date.

Treatment needs will vary considerably depending on the patient’s baseline skin health. As dermatologists, our patients depend greatly on us to help them look and feel their best, especially during a time when they are about to embark on a new journey like marriage. Patients need to be given realistic treatment options and time frames to achieve their goals. Whether the goal is treating acne or acne scars, starting or fine-tuning cosmetic treatments, or deciding on a skin-care regimen, the bottom line is making an appointment with the dermatologist early – 6-12 months in advance, if possible – to figure out the right plan.
 

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
 

Planning a wedding doesn’t just involve decisions on venues, vows, guests, food, and décor, but also on the betrothed couple’s appearance. Memories and photographs from this day last a lifetime, so it is understandable that people may want to and feel pressured to look their best on this important day – which along with the pressures of planning a wedding, can lead to unnecessary stress, increased cortisol, and unexpected acne and other skin issues.

llhedgehogll/Thinkstock

Because of a complete absence of wedding skin recommendations in the dermatology literature, Winklemann R et al. recently published a paper titled “Wedding Dermatology: A proposed timeline to optimize skin clearance and the avoidance of a true dermatologic emergency” (SKIN The Journal of Cutaneous Medicine 2019 Mar;3[2]:159-60). He focused on acne, using the American Academy of Dermatology acne treatment guidelines and expert opinion, they point out that other than intralesional corticosteroids (which take 0-14 days to have an effect), the majority of acne treatments require at least 3-12 months to achieve clearance or improvement.

This proposed treatment timeline makes sense given that skin cell turnover on the face takes about 6-8 weeks; therefore, it may take that long for acne lesions to resolve or for treatment to have an effect.

Besides acne treatment, cosmetic treatments also have varying healing times and may require multiple sessions with time in between treatments for optimal results. For instance, treatment of photoaging with intense pulsed light or nonablative fractionated resurfacing may require three to six treatments, typically spaced 1 month apart.

Botulinum toxin treatments may take up to 2 weeks to kick in fully, then last 3-4 months. While the lead time for botulinum toxin to kick in is relatively short, I advise people not to get their first botulinum toxin 2 weeks before their wedding. Sometimes, having this treatment 4-6 weeks prior to the wedding date provides enough time for botulinum toxin to kick in – and to start wearing off to the point that the patient has the desired cosmetic effect, but still has some movement for the desired emotional facial expressions on the wedding day. Some patients also may require touch-ups, optimally at the 2-week window, once the botulinum toxin effect has fully kicked in.

With any injectable, there may be bruising and swelling that can take a week or so to heal, even when the bruises are treated with pulse dye laser used to make bruises resolve more quickly. Even a facial may result in blemishes that take a few days to 1-2 weeks to heal, especially with extractions. As such, a facial, especially a hydrafacial, may be beneficial before one’s wedding, but I would recommend having them done at least once or twice to assess an individual’s recovery time (if any) prior to the actual wedding date.

Treatment needs will vary considerably depending on the patient’s baseline skin health. As dermatologists, our patients depend greatly on us to help them look and feel their best, especially during a time when they are about to embark on a new journey like marriage. Patients need to be given realistic treatment options and time frames to achieve their goals. Whether the goal is treating acne or acne scars, starting or fine-tuning cosmetic treatments, or deciding on a skin-care regimen, the bottom line is making an appointment with the dermatologist early – 6-12 months in advance, if possible – to figure out the right plan.
 

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
 

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.