With coronavirus disease (COVID-19) reaching epidemic proportions, many US children are growing increasingly anxious about what this means for their own health and safety and that of their friends and family.

The constantly changing numbers of people affected by the virus and the evolving situation mean daily life for many children is affected in some way, with school trips, sports tournaments, and family vacations being postponed or canceled.

All children may have a heightened level of worry, and some who are normally anxious might be obsessing more about handwashing or getting sick.

Experts say there are ways to manage this fear to help children feel safe and appropriately informed.

Clinicians and other adults should provide children with honest and accurate information geared to their age and developmental level, said David Fassler, MD, clinical professor of psychiatry, University of Vermont Larner College of Medicine, Burlington, and member of the Consumer Issues Committee of the American Academy of Child and Adolescent Psychiatry.

That said, it’s also acceptable to let children know that some questions can’t be answered, said Fassler.
 

Be truthful, calm

“This is partly because the information keeps changing as we learn more about how the virus spreads, how to best protect communities, and how to treat people who get sick,” he added.

Clinicians and parents should remind children “that there are a lot of adults who are working very hard to keep them safe,” said Eli R. Lebowitz, PhD, associate professor in the Child Study Center, Yale School of Medicine, New Haven, Connecticut, who directs a program for anxiety.

It’s important for adults to pay attention not only to what they say to children but also how they say it, said Lebowitz. He highlighted the importance of talking about the virus “in a calm and matter-of-fact way” rather than in an anxious way.

“If you look scared or tense or your voice is conveying that you’re really scared, the child is going to absorb that and feel anxious as well,” he noted.

This advice also applies when adults are discussing the issue among themselves. They should be aware that “children are listening” and are picking up any anxiety or panic adults are expressing.

Children are soaking up information about this virus from the Internet, the media, friends, teachers, and elsewhere. Lebowitz suggests asking children what they have already heard, which provides an opportunity to correct rumors and inaccurate information.

“A child might have a very inflated sense of what the actual risk is. For example, they may think that anyone who gets the virus dies,” he said.
 

Myth busting

Adults should let children know that not everything they hear from friends or on the Internet “is necessarily correct,” he added.

Some children who have experienced serious illness or losses may be particularly vulnerable to experiencing intense reactions to graphic news reports or images of illness or death and may need extra support, said Fassler.

Adults could use the “framework of knowledge” that children already have, said Lebowitz. He noted that all children are aware of sickness.

“They know people get sick, and they themselves have probably been sick, so you can tell them that this is a sickness like a bad flu,” he said.

Children should be encouraged to approach adults they trust, such as their pediatrician, a parent, or a teacher, with their questions, said Lebowitz. “Those are the people who are able to give them the most accurate information.”

Fassler noted that accurate, up-to-date information is available via fact sheets developed by the Centers for Disease Control and Prevention and the World Health Organization.

Although it’s helpful and appropriate to be reassuring, Fassler advises not to make unrealistic promises.

“It’s fine to tell kids that you’ll deal with whatever happens, even if it means altering travel plans or work schedules, but you can’t promise that no one in your state or community will get sick,” he said.
 

Maintain healthy habits

Physicians and other adults can tell children “in an age-appropriate way” how the virus is transmitted and what the symptoms are, but it’s important to emphasize that most people who are sick don’t have COVID-19, said Lebowitz.

“I would emphasize that the people who are the sickest are the elderly who are already sick, rather than healthy younger people,” he said.

Lebowitz recommends continuing to follow guidelines on staying healthy, including coughing into a sleeve instead of your hand and regular handwashing.

It’s also important at this time for children to maintain healthy habits – getting enough physical activity and sleep, eating well, and being outside – because this regime will go a long way toward reducing anxiety, said Lebowitz. Deep breathing and muscle-relaxing exercises can also help, he said.

Lebowitz also suggests maintaining a supportive attitude and showing “some acceptance and validation of what children are feeling, as well as some confidence that they can cope and tolerate feeling uncomfortable sometimes, that they can handle some anxiety.”

While accepting that the child could be anxious, it’s important not to encourage excessive avoidance or unhealthy coping strategies. Fassler and Lebowitz agree that children who are overly anxious or preoccupied with concerns about the coronavirus should be evaluated by a trained, qualified mental health professional.

Signs that a child may need additional help include ongoing sleep difficulties, intrusive thoughts or worries, obsessive-compulsive behaviors, or reluctance or refusal to go to school, said Fassler.

The good news is that most children are resilient, said Fassler. “They’ll adjust, adapt, and go on with their lives.”

This article first appeared on Medscape.com.

With coronavirus disease (COVID-19) reaching epidemic proportions, many US children are growing increasingly anxious about what this means for their own health and safety and that of their friends and family.

The constantly changing numbers of people affected by the virus and the evolving situation mean daily life for many children is affected in some way, with school trips, sports tournaments, and family vacations being postponed or canceled.

All children may have a heightened level of worry, and some who are normally anxious might be obsessing more about handwashing or getting sick.

Experts say there are ways to manage this fear to help children feel safe and appropriately informed.

Clinicians and other adults should provide children with honest and accurate information geared to their age and developmental level, said David Fassler, MD, clinical professor of psychiatry, University of Vermont Larner College of Medicine, Burlington, and member of the Consumer Issues Committee of the American Academy of Child and Adolescent Psychiatry.

That said, it’s also acceptable to let children know that some questions can’t be answered, said Fassler.
 

Be truthful, calm

“This is partly because the information keeps changing as we learn more about how the virus spreads, how to best protect communities, and how to treat people who get sick,” he added.

Clinicians and parents should remind children “that there are a lot of adults who are working very hard to keep them safe,” said Eli R. Lebowitz, PhD, associate professor in the Child Study Center, Yale School of Medicine, New Haven, Connecticut, who directs a program for anxiety.

It’s important for adults to pay attention not only to what they say to children but also how they say it, said Lebowitz. He highlighted the importance of talking about the virus “in a calm and matter-of-fact way” rather than in an anxious way.

“If you look scared or tense or your voice is conveying that you’re really scared, the child is going to absorb that and feel anxious as well,” he noted.

This advice also applies when adults are discussing the issue among themselves. They should be aware that “children are listening” and are picking up any anxiety or panic adults are expressing.

Children are soaking up information about this virus from the Internet, the media, friends, teachers, and elsewhere. Lebowitz suggests asking children what they have already heard, which provides an opportunity to correct rumors and inaccurate information.

“A child might have a very inflated sense of what the actual risk is. For example, they may think that anyone who gets the virus dies,” he said.
 

Myth busting

Adults should let children know that not everything they hear from friends or on the Internet “is necessarily correct,” he added.

Some children who have experienced serious illness or losses may be particularly vulnerable to experiencing intense reactions to graphic news reports or images of illness or death and may need extra support, said Fassler.

Adults could use the “framework of knowledge” that children already have, said Lebowitz. He noted that all children are aware of sickness.

“They know people get sick, and they themselves have probably been sick, so you can tell them that this is a sickness like a bad flu,” he said.

Children should be encouraged to approach adults they trust, such as their pediatrician, a parent, or a teacher, with their questions, said Lebowitz. “Those are the people who are able to give them the most accurate information.”

Fassler noted that accurate, up-to-date information is available via fact sheets developed by the Centers for Disease Control and Prevention and the World Health Organization.

Although it’s helpful and appropriate to be reassuring, Fassler advises not to make unrealistic promises.

“It’s fine to tell kids that you’ll deal with whatever happens, even if it means altering travel plans or work schedules, but you can’t promise that no one in your state or community will get sick,” he said.
 

Maintain healthy habits

Physicians and other adults can tell children “in an age-appropriate way” how the virus is transmitted and what the symptoms are, but it’s important to emphasize that most people who are sick don’t have COVID-19, said Lebowitz.

“I would emphasize that the people who are the sickest are the elderly who are already sick, rather than healthy younger people,” he said.

Lebowitz recommends continuing to follow guidelines on staying healthy, including coughing into a sleeve instead of your hand and regular handwashing.

It’s also important at this time for children to maintain healthy habits – getting enough physical activity and sleep, eating well, and being outside – because this regime will go a long way toward reducing anxiety, said Lebowitz. Deep breathing and muscle-relaxing exercises can also help, he said.

Lebowitz also suggests maintaining a supportive attitude and showing “some acceptance and validation of what children are feeling, as well as some confidence that they can cope and tolerate feeling uncomfortable sometimes, that they can handle some anxiety.”

While accepting that the child could be anxious, it’s important not to encourage excessive avoidance or unhealthy coping strategies. Fassler and Lebowitz agree that children who are overly anxious or preoccupied with concerns about the coronavirus should be evaluated by a trained, qualified mental health professional.

Signs that a child may need additional help include ongoing sleep difficulties, intrusive thoughts or worries, obsessive-compulsive behaviors, or reluctance or refusal to go to school, said Fassler.

The good news is that most children are resilient, said Fassler. “They’ll adjust, adapt, and go on with their lives.”

This article first appeared on Medscape.com.

With coronavirus disease (COVID-19) reaching epidemic proportions, many US children are growing increasingly anxious about what this means for their own health and safety and that of their friends and family.

The constantly changing numbers of people affected by the virus and the evolving situation mean daily life for many children is affected in some way, with school trips, sports tournaments, and family vacations being postponed or canceled.

All children may have a heightened level of worry, and some who are normally anxious might be obsessing more about handwashing or getting sick.

Experts say there are ways to manage this fear to help children feel safe and appropriately informed.

Clinicians and other adults should provide children with honest and accurate information geared to their age and developmental level, said David Fassler, MD, clinical professor of psychiatry, University of Vermont Larner College of Medicine, Burlington, and member of the Consumer Issues Committee of the American Academy of Child and Adolescent Psychiatry.

That said, it’s also acceptable to let children know that some questions can’t be answered, said Fassler.
 

Be truthful, calm

“This is partly because the information keeps changing as we learn more about how the virus spreads, how to best protect communities, and how to treat people who get sick,” he added.

Clinicians and parents should remind children “that there are a lot of adults who are working very hard to keep them safe,” said Eli R. Lebowitz, PhD, associate professor in the Child Study Center, Yale School of Medicine, New Haven, Connecticut, who directs a program for anxiety.

It’s important for adults to pay attention not only to what they say to children but also how they say it, said Lebowitz. He highlighted the importance of talking about the virus “in a calm and matter-of-fact way” rather than in an anxious way.

“If you look scared or tense or your voice is conveying that you’re really scared, the child is going to absorb that and feel anxious as well,” he noted.

This advice also applies when adults are discussing the issue among themselves. They should be aware that “children are listening” and are picking up any anxiety or panic adults are expressing.

Children are soaking up information about this virus from the Internet, the media, friends, teachers, and elsewhere. Lebowitz suggests asking children what they have already heard, which provides an opportunity to correct rumors and inaccurate information.

“A child might have a very inflated sense of what the actual risk is. For example, they may think that anyone who gets the virus dies,” he said.
 

Myth busting

Adults should let children know that not everything they hear from friends or on the Internet “is necessarily correct,” he added.

Some children who have experienced serious illness or losses may be particularly vulnerable to experiencing intense reactions to graphic news reports or images of illness or death and may need extra support, said Fassler.

Adults could use the “framework of knowledge” that children already have, said Lebowitz. He noted that all children are aware of sickness.

“They know people get sick, and they themselves have probably been sick, so you can tell them that this is a sickness like a bad flu,” he said.

Children should be encouraged to approach adults they trust, such as their pediatrician, a parent, or a teacher, with their questions, said Lebowitz. “Those are the people who are able to give them the most accurate information.”

Fassler noted that accurate, up-to-date information is available via fact sheets developed by the Centers for Disease Control and Prevention and the World Health Organization.

Although it’s helpful and appropriate to be reassuring, Fassler advises not to make unrealistic promises.

“It’s fine to tell kids that you’ll deal with whatever happens, even if it means altering travel plans or work schedules, but you can’t promise that no one in your state or community will get sick,” he said.
 

Maintain healthy habits

Physicians and other adults can tell children “in an age-appropriate way” how the virus is transmitted and what the symptoms are, but it’s important to emphasize that most people who are sick don’t have COVID-19, said Lebowitz.

“I would emphasize that the people who are the sickest are the elderly who are already sick, rather than healthy younger people,” he said.

Lebowitz recommends continuing to follow guidelines on staying healthy, including coughing into a sleeve instead of your hand and regular handwashing.

It’s also important at this time for children to maintain healthy habits – getting enough physical activity and sleep, eating well, and being outside – because this regime will go a long way toward reducing anxiety, said Lebowitz. Deep breathing and muscle-relaxing exercises can also help, he said.

Lebowitz also suggests maintaining a supportive attitude and showing “some acceptance and validation of what children are feeling, as well as some confidence that they can cope and tolerate feeling uncomfortable sometimes, that they can handle some anxiety.”

While accepting that the child could be anxious, it’s important not to encourage excessive avoidance or unhealthy coping strategies. Fassler and Lebowitz agree that children who are overly anxious or preoccupied with concerns about the coronavirus should be evaluated by a trained, qualified mental health professional.

Signs that a child may need additional help include ongoing sleep difficulties, intrusive thoughts or worries, obsessive-compulsive behaviors, or reluctance or refusal to go to school, said Fassler.

The good news is that most children are resilient, said Fassler. “They’ll adjust, adapt, and go on with their lives.”

This article first appeared on Medscape.com.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

WEST PALM BEACH, FLA. – The use of a disease-modifying therapy (DMT) is common among older patients with multiple sclerosis even though DMTs may be less effective in this population, according to a review of clinical trial results and registry data.

MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.

“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.

The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”

In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.

Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.

A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.

Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.

jremaly@mdedge.com

SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Nonmyeloablative haploidentical allo-bone marrow transplantation with posttransplantation cyclophosphamide is a safe and effective treatment option for patients with chronic lymphocytic leukemia (CLL), according to a study published in Biology of Blood and Marrow Transplantation.

The number of patients undergoing haploidentical allo-BMT has increased substantially, with the advent of new graft-versus-host disease (GVHD) prophylaxis strategies, such as posttransplantation cyclophosphamide (PTCy), that reduce the risk of GVHD complications; however there have been few studies assessing the results of this treatment regimen, according to the authors.

The study assessed 64 consecutive patients with CLL between Jan. 2005 and Aug. 2018 who underwent haploidentical allo-BMT. The median age was 59 years; 4 patients (6.2%) underwent allo-BMT after first-line treatment; 20 patients (31.2%) underwent allo-BMT after second-line treatment, and 40 patients (62.5%) underwent allo-BMT after three or more lines of treatment for relapsed and/or refractory disease.

All patients received a nonmyeloablative (NMA) conditioning regimen consisting of fludarabine, cyclophosphamide, and 200 cGy total body irradiation. Patients received PTCy (i.v. 50 mg/kg per day) on days +3 and +4, along with additional GVHD prophylaxis with mycophenolate mofetil between days +5 and +35 and tacrolimus or sirolimus between days +5 and +180.

For all 64 patients, the median duration of follow-up was 4.4 years based on the reverse Kaplan-Meier method. The 4-year overall survival (OS) was 52%, and the 4-year progression-free survival (PFS) was 37%. The 56 patients with less than 20% marrow CLL involvement before undergoing allo-BMT had a 4-year OS of 61%, a 4-year PFS of 43%, and a median OS of 4.8 years, according to the authors.

Regression analysis demonstrated that donor age, stem cell source, IGHV mutation status, or grade II-III acute GVHD did not affect risk of progression or survival.

“The majority of our patients had unfavorable risk factors, and collectively our data show that haploidentical allo-BMT with PTCy in CLL with less than 20% marrow involvement is a safe treatment option carrying a low risk of serious GVHD and other toxicities,” the researchers concluded.

The study was supported by National Institutes of Health, National Cancer Institute grants. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Suman P et al. Biol Blood Marrow Transplant. 2020 Mar 1;26:502-8. doi: 10.1016/j.bbmt.2019.11.008

Nonmyeloablative haploidentical allo-bone marrow transplantation with posttransplantation cyclophosphamide is a safe and effective treatment option for patients with chronic lymphocytic leukemia (CLL), according to a study published in Biology of Blood and Marrow Transplantation.

The number of patients undergoing haploidentical allo-BMT has increased substantially, with the advent of new graft-versus-host disease (GVHD) prophylaxis strategies, such as posttransplantation cyclophosphamide (PTCy), that reduce the risk of GVHD complications; however there have been few studies assessing the results of this treatment regimen, according to the authors.

The study assessed 64 consecutive patients with CLL between Jan. 2005 and Aug. 2018 who underwent haploidentical allo-BMT. The median age was 59 years; 4 patients (6.2%) underwent allo-BMT after first-line treatment; 20 patients (31.2%) underwent allo-BMT after second-line treatment, and 40 patients (62.5%) underwent allo-BMT after three or more lines of treatment for relapsed and/or refractory disease.

All patients received a nonmyeloablative (NMA) conditioning regimen consisting of fludarabine, cyclophosphamide, and 200 cGy total body irradiation. Patients received PTCy (i.v. 50 mg/kg per day) on days +3 and +4, along with additional GVHD prophylaxis with mycophenolate mofetil between days +5 and +35 and tacrolimus or sirolimus between days +5 and +180.

For all 64 patients, the median duration of follow-up was 4.4 years based on the reverse Kaplan-Meier method. The 4-year overall survival (OS) was 52%, and the 4-year progression-free survival (PFS) was 37%. The 56 patients with less than 20% marrow CLL involvement before undergoing allo-BMT had a 4-year OS of 61%, a 4-year PFS of 43%, and a median OS of 4.8 years, according to the authors.

Regression analysis demonstrated that donor age, stem cell source, IGHV mutation status, or grade II-III acute GVHD did not affect risk of progression or survival.

“The majority of our patients had unfavorable risk factors, and collectively our data show that haploidentical allo-BMT with PTCy in CLL with less than 20% marrow involvement is a safe treatment option carrying a low risk of serious GVHD and other toxicities,” the researchers concluded.

The study was supported by National Institutes of Health, National Cancer Institute grants. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Suman P et al. Biol Blood Marrow Transplant. 2020 Mar 1;26:502-8. doi: 10.1016/j.bbmt.2019.11.008

Nonmyeloablative haploidentical allo-bone marrow transplantation with posttransplantation cyclophosphamide is a safe and effective treatment option for patients with chronic lymphocytic leukemia (CLL), according to a study published in Biology of Blood and Marrow Transplantation.

The number of patients undergoing haploidentical allo-BMT has increased substantially, with the advent of new graft-versus-host disease (GVHD) prophylaxis strategies, such as posttransplantation cyclophosphamide (PTCy), that reduce the risk of GVHD complications; however there have been few studies assessing the results of this treatment regimen, according to the authors.

The study assessed 64 consecutive patients with CLL between Jan. 2005 and Aug. 2018 who underwent haploidentical allo-BMT. The median age was 59 years; 4 patients (6.2%) underwent allo-BMT after first-line treatment; 20 patients (31.2%) underwent allo-BMT after second-line treatment, and 40 patients (62.5%) underwent allo-BMT after three or more lines of treatment for relapsed and/or refractory disease.

All patients received a nonmyeloablative (NMA) conditioning regimen consisting of fludarabine, cyclophosphamide, and 200 cGy total body irradiation. Patients received PTCy (i.v. 50 mg/kg per day) on days +3 and +4, along with additional GVHD prophylaxis with mycophenolate mofetil between days +5 and +35 and tacrolimus or sirolimus between days +5 and +180.

For all 64 patients, the median duration of follow-up was 4.4 years based on the reverse Kaplan-Meier method. The 4-year overall survival (OS) was 52%, and the 4-year progression-free survival (PFS) was 37%. The 56 patients with less than 20% marrow CLL involvement before undergoing allo-BMT had a 4-year OS of 61%, a 4-year PFS of 43%, and a median OS of 4.8 years, according to the authors.

Regression analysis demonstrated that donor age, stem cell source, IGHV mutation status, or grade II-III acute GVHD did not affect risk of progression or survival.

“The majority of our patients had unfavorable risk factors, and collectively our data show that haploidentical allo-BMT with PTCy in CLL with less than 20% marrow involvement is a safe treatment option carrying a low risk of serious GVHD and other toxicities,” the researchers concluded.

The study was supported by National Institutes of Health, National Cancer Institute grants. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Suman P et al. Biol Blood Marrow Transplant. 2020 Mar 1;26:502-8. doi: 10.1016/j.bbmt.2019.11.008

Recently, Nicolas Badre, MD, challenged psychiatrists who care for patients involved in the legal system. He encouraged “a resurgence of personal accountability and responsibility.”

Using the chronically disenfranchised patients who are repetitiously shuttled between jails and mental hospitals as examples, he pointed out that we psychiatrists must “step up to the plate” and approach clinical problems with the attitude that “the buck stops with me.” As Dr. Badre pointed out, this is especially true when dealing with large, complex systems in which fragmented care exists without clear leadership. This, in turn, allows for a dissolution of accountability.

Accountability is a natural continuation of our training as physicians. We all remember the transition from medical student to intern, the steep learning curve as well as growth and maturation during this changeover. A dramatic transformation occurs over the course of 1 year, from medical students who tag along learning from patients to interns expected to be on their own for endless hours.

Over the course of those hours, we came to the understanding that people’s lives were in our hands. This causes a shift in our identity. This process continues throughout residency and onward in our careers. At some point, it becomes part of our innate identity as physicians or our professional sense of self – which is hard to describe to nonphysicians.

A profound example of a sense of accountability within the medical profession can be found in “How We Live,” a book by National Book Award winner Sherwin B. Nuland, MD. In the book, the late Dr. Nuland recounted how, as a 49-year-old seasoned surgeon working at Yale University, New Haven, Conn., and casually rounding on patients, he heard a frantic message: “Any general surgeon! Any general surgeon! Go immediately to the operating room – immediately – any general surgeon!”

The case involved a 42-year-old wife and mother who had been rushed to the ED after having been found in the community in a profound state of shock. In the ED, it was suspected that the patient was bleeding heavily from a ruptured tubal pregnancy. She was sped rapidly to the operating room with an undetectable blood pressure and a barely palpable pulse. The on-call ob.gyn. had been summoned from home, and he rushed to the operating room along with his department chairman.

Because the woman had lost much of her blood supply, there was no time for crossmatching. The anesthesiologist had placed large-bore intravenous lines and transfused her with O-negative blood (the universal donor blood type) to try maintain some level of blood pressure. Before she could be even fully anesthetized, the ob.gyn had made an incision in her lower abdomen. The bleeding he encountered was profound.

After a quick evaluation, the ob.gyn. realized that the blood was coming from above, not below, leading to the emergency page that Dr. Nuland heard. Dr. Nuland described bounding up the stairs three at a time. He recalled: “[A] very real apprehension had entered my mind. I might encounter a situation that was beyond me, something that I might make even worse, something that would cause me to regret for the rest of my life that I had answered the page’s insistent call instead of simply turning my back on its urgency and slinking off to my car before anyone noticed I was there.”

However, he could not see himself doing such a thing and he rushed up to the operating room because, “walking away from that kind of cry for help would have violated every precept taught me by my life and my training, and every bit of moral sense I had. … . I bear an obsessive preoccupation with accepting responsibility, amounting really to a compulsively neurotic sense of duty.”

And yet in the next few seconds, as he was running to the operating room, he wondered: “Am I about to botch something up? Will I, in one quick stroke of ineptness and fate, bring my career crashing down around my feet and with it my sense of what I am? Am I on my way to destroy an unknown patient and myself at the same time?”

In Dr. Nuland’s thoughts lie the conundrum of responsibility for physicians. Thankfully for Dr. Nuland, he was able to save the day and diagnose a rare case of rupture of an aneurysm of the splenic artery and keep the patient alive. This dramatic story involved a surgical colleague who had to make split-second decisions while a patient’s life hanged in the balance, but the same principles apply to us as psychiatrists.

Sadly, like a ruptured splenic artery, depression and other mental illnesses can end lives in vulnerable patients facing overwhelming life crises. I would note that, in the above example of the surgical patient, the “system” for saving the woman’s life was well organized and resourced to allow for a comprehensive and time-limited intervention into a life-threatening situation. There was an operating room staffed by various professionals who all had a defined role. It required the leader, Dr. Nuland, to step in, make the right diagnosis, and then issue commands to the identified professionals who all recognized his leadership and were skilled in carrying out their assigned duties. Dr. Nuland clearly was the leader once he took charge.

An outpatient psychiatrist facing a suicidal patient must deal with a different set of challenges, often involving various complex systems as well as multiple barriers. Clinical barriers include available interdisciplinary resources/personnel to assist not only with the critical encounter, but also with extended evaluation and treatment in a secure, well-resourced environment. Administrative barriers can include justifying the optimal treatment plan to payors. Our lethal patients often require both outpatient and inpatient services with sometimes-conflicting agendas. In a recent article, I pointed out some of the vexing problems that arise when communication and collaboration are poor between inpatient and outpatient psychiatrists. In such complex environments, it is less clear what is involved in the outpatient psychiatrist stepping up to the plate and asserting leadership.

An emotionally wrenching article about an emergency physician, Matthew E. Seaman, MD, who died by suicide, reminds us of the potential for suicide in a complicated patient (in this case, a medical colleague) involving complex systems. Plagued by a review of his care by the medical board (they had forced him to surrender his medical license and allowed the allegations to go public in lieu of further disciplinary proceedings), a subsequent lawsuit and an ultimate attempt by the plaintiff to obtain Dr. Seaman’s personal assets led to his worsening mental health. According to his wife, also a physician, he was getting “more depressed by the insults and assaults on his integrity and professionalism.”

Just before the investigation, he had received a 30-year pin from the American Board of Emergency Medicine for his “dedication to the specialty.” He fell into a deep depression from which he could not recover despite several psychiatric admissions and several medication trials. Along with his depression, he suffered from severe anxiety, a known risk factor for suicide. Dr. Seaman was feeling overwhelmed by the lengthy legal process targeting him as being negligent. He begged his attorney to settle the case, but his insurance carrier would not allow it. According to his wife: “All sense of human worth had been beaten out of him.”

Dr. Seaman had been known as resilient. He could handle complex ED situations, including simultaneously dealing with multiple traumas. He previously had been named in three malpractice lawsuits and had prevailed in each one. But his resilience had greatly diminished, and he became overwhelmed. He previously had, as a physician, been able to step up to the plate of accountability. But now, because of a confluence of depression and anxiety as well as the “insults and assaults on his integrity and professionalism,” he found life to be unbearable with the resulting tragic end.

So how would we as psychiatrists step up to the plate and be accountable when faced with a struggling fellow physician at risk for suicide such as Dr. Seaman?

Be aware of relevant risk factors

In addition to being aware of the usual risk factors for suicide, it would behoove us to also understand how physician suicides differ from suicides among nonphysicians.¹ For example, physicians who have died by suicide were far more likely to have experienced job-related problems than nonphysicians, but less likely to have experienced the recent death of a loved one. Also noteworthy is that physicians who end their lives were more often married. In addition, Michael F. Myers, MD, a psychiatrist who has studied physician suicides, noted in the article about Dr. Seaman that struggling physicians are likely to suffer from shame and embarrassment.
 

Consider shame, burdensomeness, and secrecy

When suicide risk factors are taught to students and professionals, rarely is shame mentioned. Perhaps it is not a common risk factor in the general population, but shame and its cousin, disgrace, are known risk factors that likely apply more to people – such as physicians – who have built a reputation over their careers. One whole chapter is given to disgrace suicides in a book about suicide notes.² A reputation often is one of the most important factors for professionals, which creates their sense of identity and, by extension, a sense of purpose in life.

When a doctor perceives that his or her reputation is being destroyed, it can produce a profound sense of shame, one of the most powerful of negative emotions.³ Another feature among completed suicides that applies more generally is perceived burdensomeness, according to Thomas E. Joiner Jr., PhD, one of the deep and innovative researchers in the field of suicidology.⁴ Once a doctor starts feeling that he has been a failure in his professional life and starts ruminating about it, the feelings of failure may generalize to other areas of his life, so that he starts feeling that he is a burden to his spouse. This, then, only increases his shame.

The issue of secrecy also is noteworthy. I was struck reading a book by Dr. Myers on physician suicide by the many spouses and family members who were caught completely unaware of problems when their spouse, a doctor, ended their lives by suicide.⁵ The doctors hid their problems well, perhaps not wanting to burden their family members. Also, if feelings of shame are an issue, then concealment tends to occur. This concealment of suicidality runs counter to the current narrative among some in the professional community that suicides are preventable (this despite the continuing increase in rates of suicide at the same time that there are increases in mental health services and suicide prevention programs).⁶

As pointed out in some of the letters quoted in Dr. Myers’s book, those who completed suicide are smart and know how to hide their symptoms well. Although Dr. Seaman’s wife, Linda Seaman, MD, was aware of her husband’s suicidality, when he eventually determined that he was going to end his life, he apparently did not reveal his more serious intention to her. Aside from spouses and family, determined suicide completers often hide their intentions from their clinicians.⁷
 

Attempt to obtain collateral information

By being aware of the usual and less-usual risk factors for suicide that our physician colleagues may present with as explained above, we can use strategies for mitigating risk. If secrecy because of shame and embarrassment prevents our physician patient from being fully candid, include the spouse or another significant family member in sessions. While the physician might hide his suicidal intent from both the clinician and spouse, it remains prudent to include the spouse in the treatment plan. Give the spouse a telephone number with which they can contact you if they notice any worrisome change in functioning or behavior. Collateral information often is helpful. (Example: Is the patient not eating, not sleeping, or giving away valued possessions?)
 

Assess for competency

In Dr. Seaman’s case, it was noted that, with a trial approaching, Dr. Seaman had written in a journal entry that he could not mentally endure a trial. “For me, the stress is overwhelming.” Such a patient, suffering from severe depression, often is unable to properly assist his attorney in his defense. The outpatient psychiatrist can notify the court or one of the attorneys that the competency of the physician patient is questionable (or express a definite opinion of incompetency), and offer the opinion that it would be best to postpone further legal action until the patient is in a more healthy state of mind.
 

Know when hospitalization is needed

Obviously, the process will go smoother if the admission is voluntary. If the patient physician resists and the psychiatrist believes that the risk for self-harm is too high for the physician patient to remain as an outpatient, try to get a spouse or family member to persuade him to be admitted. An involuntary admission opens up a whole new can of worms and may fracture the therapeutic alliance.

In the end, it might be better to take that risk rather than having a dead patient on your hands. If a hospitalization is necessary, contact the admitting psychiatrist and verbally express your concerns and the reasons why a hospitalization is needed. Ask the inpatient psychiatrist to contact you when a discharge is approaching so that you have an opportunity to ask relevant questions.

For example, during his second psychiatric admission, as the time for discharge was approaching, Dr. Seaman wrote: “I am not well enough for discharge. I am still mentally ill.” Ask the inpatient doctor whether the patient has gotten sufficiently better and he feels confident he can function as an outpatient. If there is a conflicting opinion about the readiness of the patient for discharge, notify the medical director of the service or an administrator about your concerns.
 

Ask for consultation

At any stage of the process consider getting consultation for a trusted colleague or senior clinician if you are failing to make progress. Sometimes it helps to get the perspective from a fresh pair of eyes or ears.

Get a reality check

Having recounted the inspiring story of Dr. Nuland’s magnificent efforts and joyous success in preserving a life that was on the verge of being lost in the battle against death at the last possible second, I would note the following: Surgeons will tell you that, despite their most heroic efforts and teamwork, there are times when luck runs out and the patient dies on the operating table. Also, small lapses, which all mortals are prone to despite their best efforts at conscientiousness, sometimes can lead to a bad outcome.

Similarly, in psychiatry, no matter how much effort we put into saving a life, sometimes it is all to no avail. Despite all we have learned about suicide and its risk factors, and no matter how much care we take to contain risk, our patients who are determined will find a way of ending their own lives. The vexing problem of suicide seems intractable. A suicide among our patients humbles us, but also hopefully inspires us to keep trying harder to step up to the plate of accountability.

In conclusion, for us physicians, accountability is not a facet, a trait, or even a pursuit, accountability is at the core of who are and how we define ourselves. Accountability is the reason we leap stairs three at time when we are urgently paged. Accountability is the reason malpractice lawsuits cut at the core of our self-image. Accountability allows us to always have hope for a positive outcome, despite overwhelming barriers, and gives our lives a sense of purpose.

For me, in preparing this article, accountability was reviewing and studying physician suicide and then applying best practices in risk assessment after reading the tragic story of Dr. Seaman. I hope I inspire you to do the same in the pursuit of helping our vulnerable patients.

Learning how to care for our complex patients is a never-ending journey.
 

References

1. Gold KJ. Gen Hosp Psychiatry. 2013 Jan;35(1):45-9.

2. Etkind M. ...Or Not to Be: A Collection of Suicide Notes. New York: Riverhead Books, 1997.

3. Lamia LC. Shame: A concealed, contagious, and dangerous emotion. Psychology Today. 2011 Apr 4.

4. Joiner TE. Why People Die by Suicide. Cambridge: Harvard University Press, 2005.

5. Myers MF. Why Physicians Die by Suicide. 2017.

6. National Institutes of Health. Suicide Prevention. https://www.nimh.nih.gov/health/topics/suicide-prevention/index.shtml.

7. Levy AG et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9277.
 

Dr. Kausch is a clinical and forensic psychiatrist who is on the faculty at Case Western Reserve University, Cleveland, as an assistant clinical professor. He spends most of his time seeing patients through the Akron General/Cleveland Clinic health system. He has published in the area of forensic psychiatry, addictions, pathological gambling, and suicide. He has recently taken an interest in conducting marital therapy and is now publishing in that area as well.

Recently, Nicolas Badre, MD, challenged psychiatrists who care for patients involved in the legal system. He encouraged “a resurgence of personal accountability and responsibility.”

Using the chronically disenfranchised patients who are repetitiously shuttled between jails and mental hospitals as examples, he pointed out that we psychiatrists must “step up to the plate” and approach clinical problems with the attitude that “the buck stops with me.” As Dr. Badre pointed out, this is especially true when dealing with large, complex systems in which fragmented care exists without clear leadership. This, in turn, allows for a dissolution of accountability.

Accountability is a natural continuation of our training as physicians. We all remember the transition from medical student to intern, the steep learning curve as well as growth and maturation during this changeover. A dramatic transformation occurs over the course of 1 year, from medical students who tag along learning from patients to interns expected to be on their own for endless hours.

Over the course of those hours, we came to the understanding that people’s lives were in our hands. This causes a shift in our identity. This process continues throughout residency and onward in our careers. At some point, it becomes part of our innate identity as physicians or our professional sense of self – which is hard to describe to nonphysicians.

A profound example of a sense of accountability within the medical profession can be found in “How We Live,” a book by National Book Award winner Sherwin B. Nuland, MD. In the book, the late Dr. Nuland recounted how, as a 49-year-old seasoned surgeon working at Yale University, New Haven, Conn., and casually rounding on patients, he heard a frantic message: “Any general surgeon! Any general surgeon! Go immediately to the operating room – immediately – any general surgeon!”

The case involved a 42-year-old wife and mother who had been rushed to the ED after having been found in the community in a profound state of shock. In the ED, it was suspected that the patient was bleeding heavily from a ruptured tubal pregnancy. She was sped rapidly to the operating room with an undetectable blood pressure and a barely palpable pulse. The on-call ob.gyn. had been summoned from home, and he rushed to the operating room along with his department chairman.

Because the woman had lost much of her blood supply, there was no time for crossmatching. The anesthesiologist had placed large-bore intravenous lines and transfused her with O-negative blood (the universal donor blood type) to try maintain some level of blood pressure. Before she could be even fully anesthetized, the ob.gyn had made an incision in her lower abdomen. The bleeding he encountered was profound.

After a quick evaluation, the ob.gyn. realized that the blood was coming from above, not below, leading to the emergency page that Dr. Nuland heard. Dr. Nuland described bounding up the stairs three at a time. He recalled: “[A] very real apprehension had entered my mind. I might encounter a situation that was beyond me, something that I might make even worse, something that would cause me to regret for the rest of my life that I had answered the page’s insistent call instead of simply turning my back on its urgency and slinking off to my car before anyone noticed I was there.”

However, he could not see himself doing such a thing and he rushed up to the operating room because, “walking away from that kind of cry for help would have violated every precept taught me by my life and my training, and every bit of moral sense I had. … . I bear an obsessive preoccupation with accepting responsibility, amounting really to a compulsively neurotic sense of duty.”

And yet in the next few seconds, as he was running to the operating room, he wondered: “Am I about to botch something up? Will I, in one quick stroke of ineptness and fate, bring my career crashing down around my feet and with it my sense of what I am? Am I on my way to destroy an unknown patient and myself at the same time?”

In Dr. Nuland’s thoughts lie the conundrum of responsibility for physicians. Thankfully for Dr. Nuland, he was able to save the day and diagnose a rare case of rupture of an aneurysm of the splenic artery and keep the patient alive. This dramatic story involved a surgical colleague who had to make split-second decisions while a patient’s life hanged in the balance, but the same principles apply to us as psychiatrists.

Sadly, like a ruptured splenic artery, depression and other mental illnesses can end lives in vulnerable patients facing overwhelming life crises. I would note that, in the above example of the surgical patient, the “system” for saving the woman’s life was well organized and resourced to allow for a comprehensive and time-limited intervention into a life-threatening situation. There was an operating room staffed by various professionals who all had a defined role. It required the leader, Dr. Nuland, to step in, make the right diagnosis, and then issue commands to the identified professionals who all recognized his leadership and were skilled in carrying out their assigned duties. Dr. Nuland clearly was the leader once he took charge.

An outpatient psychiatrist facing a suicidal patient must deal with a different set of challenges, often involving various complex systems as well as multiple barriers. Clinical barriers include available interdisciplinary resources/personnel to assist not only with the critical encounter, but also with extended evaluation and treatment in a secure, well-resourced environment. Administrative barriers can include justifying the optimal treatment plan to payors. Our lethal patients often require both outpatient and inpatient services with sometimes-conflicting agendas. In a recent article, I pointed out some of the vexing problems that arise when communication and collaboration are poor between inpatient and outpatient psychiatrists. In such complex environments, it is less clear what is involved in the outpatient psychiatrist stepping up to the plate and asserting leadership.

An emotionally wrenching article about an emergency physician, Matthew E. Seaman, MD, who died by suicide, reminds us of the potential for suicide in a complicated patient (in this case, a medical colleague) involving complex systems. Plagued by a review of his care by the medical board (they had forced him to surrender his medical license and allowed the allegations to go public in lieu of further disciplinary proceedings), a subsequent lawsuit and an ultimate attempt by the plaintiff to obtain Dr. Seaman’s personal assets led to his worsening mental health. According to his wife, also a physician, he was getting “more depressed by the insults and assaults on his integrity and professionalism.”

Just before the investigation, he had received a 30-year pin from the American Board of Emergency Medicine for his “dedication to the specialty.” He fell into a deep depression from which he could not recover despite several psychiatric admissions and several medication trials. Along with his depression, he suffered from severe anxiety, a known risk factor for suicide. Dr. Seaman was feeling overwhelmed by the lengthy legal process targeting him as being negligent. He begged his attorney to settle the case, but his insurance carrier would not allow it. According to his wife: “All sense of human worth had been beaten out of him.”

Dr. Seaman had been known as resilient. He could handle complex ED situations, including simultaneously dealing with multiple traumas. He previously had been named in three malpractice lawsuits and had prevailed in each one. But his resilience had greatly diminished, and he became overwhelmed. He previously had, as a physician, been able to step up to the plate of accountability. But now, because of a confluence of depression and anxiety as well as the “insults and assaults on his integrity and professionalism,” he found life to be unbearable with the resulting tragic end.

So how would we as psychiatrists step up to the plate and be accountable when faced with a struggling fellow physician at risk for suicide such as Dr. Seaman?

Be aware of relevant risk factors

In addition to being aware of the usual risk factors for suicide, it would behoove us to also understand how physician suicides differ from suicides among nonphysicians.¹ For example, physicians who have died by suicide were far more likely to have experienced job-related problems than nonphysicians, but less likely to have experienced the recent death of a loved one. Also noteworthy is that physicians who end their lives were more often married. In addition, Michael F. Myers, MD, a psychiatrist who has studied physician suicides, noted in the article about Dr. Seaman that struggling physicians are likely to suffer from shame and embarrassment.
 

Consider shame, burdensomeness, and secrecy

When suicide risk factors are taught to students and professionals, rarely is shame mentioned. Perhaps it is not a common risk factor in the general population, but shame and its cousin, disgrace, are known risk factors that likely apply more to people – such as physicians – who have built a reputation over their careers. One whole chapter is given to disgrace suicides in a book about suicide notes.² A reputation often is one of the most important factors for professionals, which creates their sense of identity and, by extension, a sense of purpose in life.

When a doctor perceives that his or her reputation is being destroyed, it can produce a profound sense of shame, one of the most powerful of negative emotions.³ Another feature among completed suicides that applies more generally is perceived burdensomeness, according to Thomas E. Joiner Jr., PhD, one of the deep and innovative researchers in the field of suicidology.⁴ Once a doctor starts feeling that he has been a failure in his professional life and starts ruminating about it, the feelings of failure may generalize to other areas of his life, so that he starts feeling that he is a burden to his spouse. This, then, only increases his shame.

The issue of secrecy also is noteworthy. I was struck reading a book by Dr. Myers on physician suicide by the many spouses and family members who were caught completely unaware of problems when their spouse, a doctor, ended their lives by suicide.⁵ The doctors hid their problems well, perhaps not wanting to burden their family members. Also, if feelings of shame are an issue, then concealment tends to occur. This concealment of suicidality runs counter to the current narrative among some in the professional community that suicides are preventable (this despite the continuing increase in rates of suicide at the same time that there are increases in mental health services and suicide prevention programs).⁶

As pointed out in some of the letters quoted in Dr. Myers’s book, those who completed suicide are smart and know how to hide their symptoms well. Although Dr. Seaman’s wife, Linda Seaman, MD, was aware of her husband’s suicidality, when he eventually determined that he was going to end his life, he apparently did not reveal his more serious intention to her. Aside from spouses and family, determined suicide completers often hide their intentions from their clinicians.⁷
 

Attempt to obtain collateral information

By being aware of the usual and less-usual risk factors for suicide that our physician colleagues may present with as explained above, we can use strategies for mitigating risk. If secrecy because of shame and embarrassment prevents our physician patient from being fully candid, include the spouse or another significant family member in sessions. While the physician might hide his suicidal intent from both the clinician and spouse, it remains prudent to include the spouse in the treatment plan. Give the spouse a telephone number with which they can contact you if they notice any worrisome change in functioning or behavior. Collateral information often is helpful. (Example: Is the patient not eating, not sleeping, or giving away valued possessions?)
 

Assess for competency

In Dr. Seaman’s case, it was noted that, with a trial approaching, Dr. Seaman had written in a journal entry that he could not mentally endure a trial. “For me, the stress is overwhelming.” Such a patient, suffering from severe depression, often is unable to properly assist his attorney in his defense. The outpatient psychiatrist can notify the court or one of the attorneys that the competency of the physician patient is questionable (or express a definite opinion of incompetency), and offer the opinion that it would be best to postpone further legal action until the patient is in a more healthy state of mind.
 

Know when hospitalization is needed

Obviously, the process will go smoother if the admission is voluntary. If the patient physician resists and the psychiatrist believes that the risk for self-harm is too high for the physician patient to remain as an outpatient, try to get a spouse or family member to persuade him to be admitted. An involuntary admission opens up a whole new can of worms and may fracture the therapeutic alliance.

In the end, it might be better to take that risk rather than having a dead patient on your hands. If a hospitalization is necessary, contact the admitting psychiatrist and verbally express your concerns and the reasons why a hospitalization is needed. Ask the inpatient psychiatrist to contact you when a discharge is approaching so that you have an opportunity to ask relevant questions.

For example, during his second psychiatric admission, as the time for discharge was approaching, Dr. Seaman wrote: “I am not well enough for discharge. I am still mentally ill.” Ask the inpatient doctor whether the patient has gotten sufficiently better and he feels confident he can function as an outpatient. If there is a conflicting opinion about the readiness of the patient for discharge, notify the medical director of the service or an administrator about your concerns.
 

Ask for consultation

At any stage of the process consider getting consultation for a trusted colleague or senior clinician if you are failing to make progress. Sometimes it helps to get the perspective from a fresh pair of eyes or ears.

Get a reality check

Having recounted the inspiring story of Dr. Nuland’s magnificent efforts and joyous success in preserving a life that was on the verge of being lost in the battle against death at the last possible second, I would note the following: Surgeons will tell you that, despite their most heroic efforts and teamwork, there are times when luck runs out and the patient dies on the operating table. Also, small lapses, which all mortals are prone to despite their best efforts at conscientiousness, sometimes can lead to a bad outcome.

Similarly, in psychiatry, no matter how much effort we put into saving a life, sometimes it is all to no avail. Despite all we have learned about suicide and its risk factors, and no matter how much care we take to contain risk, our patients who are determined will find a way of ending their own lives. The vexing problem of suicide seems intractable. A suicide among our patients humbles us, but also hopefully inspires us to keep trying harder to step up to the plate of accountability.

In conclusion, for us physicians, accountability is not a facet, a trait, or even a pursuit, accountability is at the core of who are and how we define ourselves. Accountability is the reason we leap stairs three at time when we are urgently paged. Accountability is the reason malpractice lawsuits cut at the core of our self-image. Accountability allows us to always have hope for a positive outcome, despite overwhelming barriers, and gives our lives a sense of purpose.

For me, in preparing this article, accountability was reviewing and studying physician suicide and then applying best practices in risk assessment after reading the tragic story of Dr. Seaman. I hope I inspire you to do the same in the pursuit of helping our vulnerable patients.

Learning how to care for our complex patients is a never-ending journey.
 

References

1. Gold KJ. Gen Hosp Psychiatry. 2013 Jan;35(1):45-9.

2. Etkind M. ...Or Not to Be: A Collection of Suicide Notes. New York: Riverhead Books, 1997.

3. Lamia LC. Shame: A concealed, contagious, and dangerous emotion. Psychology Today. 2011 Apr 4.

4. Joiner TE. Why People Die by Suicide. Cambridge: Harvard University Press, 2005.

5. Myers MF. Why Physicians Die by Suicide. 2017.

6. National Institutes of Health. Suicide Prevention. https://www.nimh.nih.gov/health/topics/suicide-prevention/index.shtml.

7. Levy AG et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9277.
 

Dr. Kausch is a clinical and forensic psychiatrist who is on the faculty at Case Western Reserve University, Cleveland, as an assistant clinical professor. He spends most of his time seeing patients through the Akron General/Cleveland Clinic health system. He has published in the area of forensic psychiatry, addictions, pathological gambling, and suicide. He has recently taken an interest in conducting marital therapy and is now publishing in that area as well.

Recently, Nicolas Badre, MD, challenged psychiatrists who care for patients involved in the legal system. He encouraged “a resurgence of personal accountability and responsibility.”

Using the chronically disenfranchised patients who are repetitiously shuttled between jails and mental hospitals as examples, he pointed out that we psychiatrists must “step up to the plate” and approach clinical problems with the attitude that “the buck stops with me.” As Dr. Badre pointed out, this is especially true when dealing with large, complex systems in which fragmented care exists without clear leadership. This, in turn, allows for a dissolution of accountability.

Accountability is a natural continuation of our training as physicians. We all remember the transition from medical student to intern, the steep learning curve as well as growth and maturation during this changeover. A dramatic transformation occurs over the course of 1 year, from medical students who tag along learning from patients to interns expected to be on their own for endless hours.

Over the course of those hours, we came to the understanding that people’s lives were in our hands. This causes a shift in our identity. This process continues throughout residency and onward in our careers. At some point, it becomes part of our innate identity as physicians or our professional sense of self – which is hard to describe to nonphysicians.

A profound example of a sense of accountability within the medical profession can be found in “How We Live,” a book by National Book Award winner Sherwin B. Nuland, MD. In the book, the late Dr. Nuland recounted how, as a 49-year-old seasoned surgeon working at Yale University, New Haven, Conn., and casually rounding on patients, he heard a frantic message: “Any general surgeon! Any general surgeon! Go immediately to the operating room – immediately – any general surgeon!”

The case involved a 42-year-old wife and mother who had been rushed to the ED after having been found in the community in a profound state of shock. In the ED, it was suspected that the patient was bleeding heavily from a ruptured tubal pregnancy. She was sped rapidly to the operating room with an undetectable blood pressure and a barely palpable pulse. The on-call ob.gyn. had been summoned from home, and he rushed to the operating room along with his department chairman.

Because the woman had lost much of her blood supply, there was no time for crossmatching. The anesthesiologist had placed large-bore intravenous lines and transfused her with O-negative blood (the universal donor blood type) to try maintain some level of blood pressure. Before she could be even fully anesthetized, the ob.gyn had made an incision in her lower abdomen. The bleeding he encountered was profound.

After a quick evaluation, the ob.gyn. realized that the blood was coming from above, not below, leading to the emergency page that Dr. Nuland heard. Dr. Nuland described bounding up the stairs three at a time. He recalled: “[A] very real apprehension had entered my mind. I might encounter a situation that was beyond me, something that I might make even worse, something that would cause me to regret for the rest of my life that I had answered the page’s insistent call instead of simply turning my back on its urgency and slinking off to my car before anyone noticed I was there.”

However, he could not see himself doing such a thing and he rushed up to the operating room because, “walking away from that kind of cry for help would have violated every precept taught me by my life and my training, and every bit of moral sense I had. … . I bear an obsessive preoccupation with accepting responsibility, amounting really to a compulsively neurotic sense of duty.”

And yet in the next few seconds, as he was running to the operating room, he wondered: “Am I about to botch something up? Will I, in one quick stroke of ineptness and fate, bring my career crashing down around my feet and with it my sense of what I am? Am I on my way to destroy an unknown patient and myself at the same time?”

In Dr. Nuland’s thoughts lie the conundrum of responsibility for physicians. Thankfully for Dr. Nuland, he was able to save the day and diagnose a rare case of rupture of an aneurysm of the splenic artery and keep the patient alive. This dramatic story involved a surgical colleague who had to make split-second decisions while a patient’s life hanged in the balance, but the same principles apply to us as psychiatrists.

Sadly, like a ruptured splenic artery, depression and other mental illnesses can end lives in vulnerable patients facing overwhelming life crises. I would note that, in the above example of the surgical patient, the “system” for saving the woman’s life was well organized and resourced to allow for a comprehensive and time-limited intervention into a life-threatening situation. There was an operating room staffed by various professionals who all had a defined role. It required the leader, Dr. Nuland, to step in, make the right diagnosis, and then issue commands to the identified professionals who all recognized his leadership and were skilled in carrying out their assigned duties. Dr. Nuland clearly was the leader once he took charge.

An outpatient psychiatrist facing a suicidal patient must deal with a different set of challenges, often involving various complex systems as well as multiple barriers. Clinical barriers include available interdisciplinary resources/personnel to assist not only with the critical encounter, but also with extended evaluation and treatment in a secure, well-resourced environment. Administrative barriers can include justifying the optimal treatment plan to payors. Our lethal patients often require both outpatient and inpatient services with sometimes-conflicting agendas. In a recent article, I pointed out some of the vexing problems that arise when communication and collaboration are poor between inpatient and outpatient psychiatrists. In such complex environments, it is less clear what is involved in the outpatient psychiatrist stepping up to the plate and asserting leadership.

An emotionally wrenching article about an emergency physician, Matthew E. Seaman, MD, who died by suicide, reminds us of the potential for suicide in a complicated patient (in this case, a medical colleague) involving complex systems. Plagued by a review of his care by the medical board (they had forced him to surrender his medical license and allowed the allegations to go public in lieu of further disciplinary proceedings), a subsequent lawsuit and an ultimate attempt by the plaintiff to obtain Dr. Seaman’s personal assets led to his worsening mental health. According to his wife, also a physician, he was getting “more depressed by the insults and assaults on his integrity and professionalism.”

Just before the investigation, he had received a 30-year pin from the American Board of Emergency Medicine for his “dedication to the specialty.” He fell into a deep depression from which he could not recover despite several psychiatric admissions and several medication trials. Along with his depression, he suffered from severe anxiety, a known risk factor for suicide. Dr. Seaman was feeling overwhelmed by the lengthy legal process targeting him as being negligent. He begged his attorney to settle the case, but his insurance carrier would not allow it. According to his wife: “All sense of human worth had been beaten out of him.”

Dr. Seaman had been known as resilient. He could handle complex ED situations, including simultaneously dealing with multiple traumas. He previously had been named in three malpractice lawsuits and had prevailed in each one. But his resilience had greatly diminished, and he became overwhelmed. He previously had, as a physician, been able to step up to the plate of accountability. But now, because of a confluence of depression and anxiety as well as the “insults and assaults on his integrity and professionalism,” he found life to be unbearable with the resulting tragic end.

So how would we as psychiatrists step up to the plate and be accountable when faced with a struggling fellow physician at risk for suicide such as Dr. Seaman?

Be aware of relevant risk factors

In addition to being aware of the usual risk factors for suicide, it would behoove us to also understand how physician suicides differ from suicides among nonphysicians.¹ For example, physicians who have died by suicide were far more likely to have experienced job-related problems than nonphysicians, but less likely to have experienced the recent death of a loved one. Also noteworthy is that physicians who end their lives were more often married. In addition, Michael F. Myers, MD, a psychiatrist who has studied physician suicides, noted in the article about Dr. Seaman that struggling physicians are likely to suffer from shame and embarrassment.
 

Consider shame, burdensomeness, and secrecy

When suicide risk factors are taught to students and professionals, rarely is shame mentioned. Perhaps it is not a common risk factor in the general population, but shame and its cousin, disgrace, are known risk factors that likely apply more to people – such as physicians – who have built a reputation over their careers. One whole chapter is given to disgrace suicides in a book about suicide notes.² A reputation often is one of the most important factors for professionals, which creates their sense of identity and, by extension, a sense of purpose in life.

When a doctor perceives that his or her reputation is being destroyed, it can produce a profound sense of shame, one of the most powerful of negative emotions.³ Another feature among completed suicides that applies more generally is perceived burdensomeness, according to Thomas E. Joiner Jr., PhD, one of the deep and innovative researchers in the field of suicidology.⁴ Once a doctor starts feeling that he has been a failure in his professional life and starts ruminating about it, the feelings of failure may generalize to other areas of his life, so that he starts feeling that he is a burden to his spouse. This, then, only increases his shame.

The issue of secrecy also is noteworthy. I was struck reading a book by Dr. Myers on physician suicide by the many spouses and family members who were caught completely unaware of problems when their spouse, a doctor, ended their lives by suicide.⁵ The doctors hid their problems well, perhaps not wanting to burden their family members. Also, if feelings of shame are an issue, then concealment tends to occur. This concealment of suicidality runs counter to the current narrative among some in the professional community that suicides are preventable (this despite the continuing increase in rates of suicide at the same time that there are increases in mental health services and suicide prevention programs).⁶

As pointed out in some of the letters quoted in Dr. Myers’s book, those who completed suicide are smart and know how to hide their symptoms well. Although Dr. Seaman’s wife, Linda Seaman, MD, was aware of her husband’s suicidality, when he eventually determined that he was going to end his life, he apparently did not reveal his more serious intention to her. Aside from spouses and family, determined suicide completers often hide their intentions from their clinicians.⁷
 

Attempt to obtain collateral information

By being aware of the usual and less-usual risk factors for suicide that our physician colleagues may present with as explained above, we can use strategies for mitigating risk. If secrecy because of shame and embarrassment prevents our physician patient from being fully candid, include the spouse or another significant family member in sessions. While the physician might hide his suicidal intent from both the clinician and spouse, it remains prudent to include the spouse in the treatment plan. Give the spouse a telephone number with which they can contact you if they notice any worrisome change in functioning or behavior. Collateral information often is helpful. (Example: Is the patient not eating, not sleeping, or giving away valued possessions?)
 

Assess for competency

In Dr. Seaman’s case, it was noted that, with a trial approaching, Dr. Seaman had written in a journal entry that he could not mentally endure a trial. “For me, the stress is overwhelming.” Such a patient, suffering from severe depression, often is unable to properly assist his attorney in his defense. The outpatient psychiatrist can notify the court or one of the attorneys that the competency of the physician patient is questionable (or express a definite opinion of incompetency), and offer the opinion that it would be best to postpone further legal action until the patient is in a more healthy state of mind.
 

Know when hospitalization is needed

Obviously, the process will go smoother if the admission is voluntary. If the patient physician resists and the psychiatrist believes that the risk for self-harm is too high for the physician patient to remain as an outpatient, try to get a spouse or family member to persuade him to be admitted. An involuntary admission opens up a whole new can of worms and may fracture the therapeutic alliance.

In the end, it might be better to take that risk rather than having a dead patient on your hands. If a hospitalization is necessary, contact the admitting psychiatrist and verbally express your concerns and the reasons why a hospitalization is needed. Ask the inpatient psychiatrist to contact you when a discharge is approaching so that you have an opportunity to ask relevant questions.

For example, during his second psychiatric admission, as the time for discharge was approaching, Dr. Seaman wrote: “I am not well enough for discharge. I am still mentally ill.” Ask the inpatient doctor whether the patient has gotten sufficiently better and he feels confident he can function as an outpatient. If there is a conflicting opinion about the readiness of the patient for discharge, notify the medical director of the service or an administrator about your concerns.
 

Ask for consultation

At any stage of the process consider getting consultation for a trusted colleague or senior clinician if you are failing to make progress. Sometimes it helps to get the perspective from a fresh pair of eyes or ears.

Get a reality check

Having recounted the inspiring story of Dr. Nuland’s magnificent efforts and joyous success in preserving a life that was on the verge of being lost in the battle against death at the last possible second, I would note the following: Surgeons will tell you that, despite their most heroic efforts and teamwork, there are times when luck runs out and the patient dies on the operating table. Also, small lapses, which all mortals are prone to despite their best efforts at conscientiousness, sometimes can lead to a bad outcome.

Similarly, in psychiatry, no matter how much effort we put into saving a life, sometimes it is all to no avail. Despite all we have learned about suicide and its risk factors, and no matter how much care we take to contain risk, our patients who are determined will find a way of ending their own lives. The vexing problem of suicide seems intractable. A suicide among our patients humbles us, but also hopefully inspires us to keep trying harder to step up to the plate of accountability.

In conclusion, for us physicians, accountability is not a facet, a trait, or even a pursuit, accountability is at the core of who are and how we define ourselves. Accountability is the reason we leap stairs three at time when we are urgently paged. Accountability is the reason malpractice lawsuits cut at the core of our self-image. Accountability allows us to always have hope for a positive outcome, despite overwhelming barriers, and gives our lives a sense of purpose.

For me, in preparing this article, accountability was reviewing and studying physician suicide and then applying best practices in risk assessment after reading the tragic story of Dr. Seaman. I hope I inspire you to do the same in the pursuit of helping our vulnerable patients.

Learning how to care for our complex patients is a never-ending journey.
 

References

1. Gold KJ. Gen Hosp Psychiatry. 2013 Jan;35(1):45-9.

2. Etkind M. ...Or Not to Be: A Collection of Suicide Notes. New York: Riverhead Books, 1997.

3. Lamia LC. Shame: A concealed, contagious, and dangerous emotion. Psychology Today. 2011 Apr 4.

4. Joiner TE. Why People Die by Suicide. Cambridge: Harvard University Press, 2005.

5. Myers MF. Why Physicians Die by Suicide. 2017.

6. National Institutes of Health. Suicide Prevention. https://www.nimh.nih.gov/health/topics/suicide-prevention/index.shtml.

7. Levy AG et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9277.
 

Dr. Kausch is a clinical and forensic psychiatrist who is on the faculty at Case Western Reserve University, Cleveland, as an assistant clinical professor. He spends most of his time seeing patients through the Akron General/Cleveland Clinic health system. He has published in the area of forensic psychiatry, addictions, pathological gambling, and suicide. He has recently taken an interest in conducting marital therapy and is now publishing in that area as well.

Bariatric surgery was associated with a significant reduction in the risk of colorectal cancer among obese adults in a retrospective study of more than 1 million individuals.

Although some studies have suggested that bariatric surgery may reduce the risk of obesity-associated cancers, such as colorectal cancer, other studies have shown an increased colorectal cancer risk after surgery, according to Laurent Bailly, MD, of Université Côte d’Azur in Nice, France, and colleagues.

In a study published in JAMA Surgery, Dr. Bailly and colleagues compared the incidence of colorectal cancer in obese patients who underwent bariatric surgery with the incidence in obese patients who did not have surgery and the incidence in the general population.

Using the French National Health Insurance Information System database, the researchers identified 1,045,348 obese adults aged 50-75 years who had no colorectal cancer at baseline. Of these patients, 74,131 underwent bariatric surgery and 971,217 did not. The mean age was 57.3 years in the surgery group and 63.4 years in the nonsurgery group.

The mean follow-up period was 6.2 years for patients who underwent adjustable gastric banding, 5.5 years for those with sleeve gastrectomy, 5.7 years for those who underwent gastric bypass, and 5.3 years for the nonsurgery group.
 

Results

Overall, the colorectal cancer rate was 0.6% in the surgery group and 1.3% in the nonsurgery group (P < .001).

The researchers calculated standardized incidence ratios (SIRs) to compare the risk of colorectal cancer in the study population with the risk among the French general population; in other words, the number of observed colorectal cancer cases divided by the number of expected cases.

In the surgery group, 423 cases of colorectal cancer were observed and 428 cases were expected, which leads to an SIR of 1.0. In the nonsurgery group, 12,629 cases were observed and 9,417 cases were expected, leading to an SIR of 1.34.

These results suggest patients in the nonsurgery group had a 34% higher risk of colorectal cancer compared with the general population, whereas the risk in the surgery group was similar to that in the general population.

Patients who underwent either gastric bypass or sleeve gastrectomy had fewer new colorectal cancer diagnoses (0.5% for both) compared with patients who had adjustable gastric banding (0.7%).

The researchers noted that this study was limited by several factors, including the retrospective, observational design and potential selection bias among surgery patients. However, the results were strengthened by the large study population and long-term follow-up.
 

Putting results into context

The authors of an invited commentary noted that this study is supported by results from a retrospective, U.S.-based study, which indicated that bariatric surgery has a “protective effect” against colorectal cancer (Ann Surg. 2019 Jan;269[1]:95-101).

However, these results conflict with other retrospective studies. A study of Nordic patients suggested that bariatric surgery is associated with an increased risk of colon cancer but perhaps not rectal cancer (Int J Cancer. 2019. doi: 10.1002/ijc.32770).

And a study of English patients showed an increased risk of colorectal cancer in patients who underwent gastric bypass but not in those who underwent gastric banding or sleeve gastrectomy (Br J Surg. 2018;105(12):1650-7).

These conflicting results “imply that the jury is still out on whether bariatric surgery increases or decreases” the risk of colorectal cancer, the commentators wrote. They added that future studies “must account for differences in study population (i.e., race/ethnicity and national origin), mechanistic variation in bariatric surgical type, and length of follow-up, while also distinguishing between rectal and colon cancer before the case is settled.”

This study had no outside sponsorship, and the researchers and commentators had no financial conflicts to disclose.

SOURCE: Bailly L et al. JAMA Surg. 2020 Mar 11. doi:10.1001/jamasurg.2020.0089; Davidson LE et al. JAMA Surg. 2020 Mar. 11. doi:10.1001/jamasurg.2020.0090.

Bariatric surgery was associated with a significant reduction in the risk of colorectal cancer among obese adults in a retrospective study of more than 1 million individuals.

Although some studies have suggested that bariatric surgery may reduce the risk of obesity-associated cancers, such as colorectal cancer, other studies have shown an increased colorectal cancer risk after surgery, according to Laurent Bailly, MD, of Université Côte d’Azur in Nice, France, and colleagues.

In a study published in JAMA Surgery, Dr. Bailly and colleagues compared the incidence of colorectal cancer in obese patients who underwent bariatric surgery with the incidence in obese patients who did not have surgery and the incidence in the general population.

Using the French National Health Insurance Information System database, the researchers identified 1,045,348 obese adults aged 50-75 years who had no colorectal cancer at baseline. Of these patients, 74,131 underwent bariatric surgery and 971,217 did not. The mean age was 57.3 years in the surgery group and 63.4 years in the nonsurgery group.

The mean follow-up period was 6.2 years for patients who underwent adjustable gastric banding, 5.5 years for those with sleeve gastrectomy, 5.7 years for those who underwent gastric bypass, and 5.3 years for the nonsurgery group.
 

Results

Overall, the colorectal cancer rate was 0.6% in the surgery group and 1.3% in the nonsurgery group (P < .001).

The researchers calculated standardized incidence ratios (SIRs) to compare the risk of colorectal cancer in the study population with the risk among the French general population; in other words, the number of observed colorectal cancer cases divided by the number of expected cases.

In the surgery group, 423 cases of colorectal cancer were observed and 428 cases were expected, which leads to an SIR of 1.0. In the nonsurgery group, 12,629 cases were observed and 9,417 cases were expected, leading to an SIR of 1.34.

These results suggest patients in the nonsurgery group had a 34% higher risk of colorectal cancer compared with the general population, whereas the risk in the surgery group was similar to that in the general population.

Patients who underwent either gastric bypass or sleeve gastrectomy had fewer new colorectal cancer diagnoses (0.5% for both) compared with patients who had adjustable gastric banding (0.7%).

The researchers noted that this study was limited by several factors, including the retrospective, observational design and potential selection bias among surgery patients. However, the results were strengthened by the large study population and long-term follow-up.
 

Putting results into context

The authors of an invited commentary noted that this study is supported by results from a retrospective, U.S.-based study, which indicated that bariatric surgery has a “protective effect” against colorectal cancer (Ann Surg. 2019 Jan;269[1]:95-101).

However, these results conflict with other retrospective studies. A study of Nordic patients suggested that bariatric surgery is associated with an increased risk of colon cancer but perhaps not rectal cancer (Int J Cancer. 2019. doi: 10.1002/ijc.32770).

And a study of English patients showed an increased risk of colorectal cancer in patients who underwent gastric bypass but not in those who underwent gastric banding or sleeve gastrectomy (Br J Surg. 2018;105(12):1650-7).

These conflicting results “imply that the jury is still out on whether bariatric surgery increases or decreases” the risk of colorectal cancer, the commentators wrote. They added that future studies “must account for differences in study population (i.e., race/ethnicity and national origin), mechanistic variation in bariatric surgical type, and length of follow-up, while also distinguishing between rectal and colon cancer before the case is settled.”

This study had no outside sponsorship, and the researchers and commentators had no financial conflicts to disclose.

SOURCE: Bailly L et al. JAMA Surg. 2020 Mar 11. doi:10.1001/jamasurg.2020.0089; Davidson LE et al. JAMA Surg. 2020 Mar. 11. doi:10.1001/jamasurg.2020.0090.

Bariatric surgery was associated with a significant reduction in the risk of colorectal cancer among obese adults in a retrospective study of more than 1 million individuals.

Although some studies have suggested that bariatric surgery may reduce the risk of obesity-associated cancers, such as colorectal cancer, other studies have shown an increased colorectal cancer risk after surgery, according to Laurent Bailly, MD, of Université Côte d’Azur in Nice, France, and colleagues.

In a study published in JAMA Surgery, Dr. Bailly and colleagues compared the incidence of colorectal cancer in obese patients who underwent bariatric surgery with the incidence in obese patients who did not have surgery and the incidence in the general population.

Using the French National Health Insurance Information System database, the researchers identified 1,045,348 obese adults aged 50-75 years who had no colorectal cancer at baseline. Of these patients, 74,131 underwent bariatric surgery and 971,217 did not. The mean age was 57.3 years in the surgery group and 63.4 years in the nonsurgery group.

The mean follow-up period was 6.2 years for patients who underwent adjustable gastric banding, 5.5 years for those with sleeve gastrectomy, 5.7 years for those who underwent gastric bypass, and 5.3 years for the nonsurgery group.
 

Results

Overall, the colorectal cancer rate was 0.6% in the surgery group and 1.3% in the nonsurgery group (P < .001).

The researchers calculated standardized incidence ratios (SIRs) to compare the risk of colorectal cancer in the study population with the risk among the French general population; in other words, the number of observed colorectal cancer cases divided by the number of expected cases.

In the surgery group, 423 cases of colorectal cancer were observed and 428 cases were expected, which leads to an SIR of 1.0. In the nonsurgery group, 12,629 cases were observed and 9,417 cases were expected, leading to an SIR of 1.34.

These results suggest patients in the nonsurgery group had a 34% higher risk of colorectal cancer compared with the general population, whereas the risk in the surgery group was similar to that in the general population.

Patients who underwent either gastric bypass or sleeve gastrectomy had fewer new colorectal cancer diagnoses (0.5% for both) compared with patients who had adjustable gastric banding (0.7%).

The researchers noted that this study was limited by several factors, including the retrospective, observational design and potential selection bias among surgery patients. However, the results were strengthened by the large study population and long-term follow-up.
 

Putting results into context

The authors of an invited commentary noted that this study is supported by results from a retrospective, U.S.-based study, which indicated that bariatric surgery has a “protective effect” against colorectal cancer (Ann Surg. 2019 Jan;269[1]:95-101).

However, these results conflict with other retrospective studies. A study of Nordic patients suggested that bariatric surgery is associated with an increased risk of colon cancer but perhaps not rectal cancer (Int J Cancer. 2019. doi: 10.1002/ijc.32770).

And a study of English patients showed an increased risk of colorectal cancer in patients who underwent gastric bypass but not in those who underwent gastric banding or sleeve gastrectomy (Br J Surg. 2018;105(12):1650-7).

These conflicting results “imply that the jury is still out on whether bariatric surgery increases or decreases” the risk of colorectal cancer, the commentators wrote. They added that future studies “must account for differences in study population (i.e., race/ethnicity and national origin), mechanistic variation in bariatric surgical type, and length of follow-up, while also distinguishing between rectal and colon cancer before the case is settled.”

This study had no outside sponsorship, and the researchers and commentators had no financial conflicts to disclose.

SOURCE: Bailly L et al. JAMA Surg. 2020 Mar 11. doi:10.1001/jamasurg.2020.0089; Davidson LE et al. JAMA Surg. 2020 Mar. 11. doi:10.1001/jamasurg.2020.0090.

Read more

Our sixth annual Rare Neurological Disease Special Report is our biggest issue yet. It is very gratifying to know we are part of the rare disease community and witness to some of the exciting developments that are transforming this field. There are many newly approved therapies highlighted in the articles in this issue, as well as brief profiles of a number of research groups within the NIH’s Rare Diseases Clinical Research Network  and an intriguing profile of how the Netflix show Diagnosis used crowdsourcing to solve medical mysteries, many of which involved rare neurologic conditions. That’s just a sampling of what this issue has to offer. There are too many articles to mention each one, but I hope you take the time to read the entire issue.

—Glenn S. Williams, vice president, group editor, Neurology Reviews

Read more

Read more

Our sixth annual Rare Neurological Disease Special Report is our biggest issue yet. It is very gratifying to know we are part of the rare disease community and witness to some of the exciting developments that are transforming this field. There are many newly approved therapies highlighted in the articles in this issue, as well as brief profiles of a number of research groups within the NIH’s Rare Diseases Clinical Research Network  and an intriguing profile of how the Netflix show Diagnosis used crowdsourcing to solve medical mysteries, many of which involved rare neurologic conditions. That’s just a sampling of what this issue has to offer. There are too many articles to mention each one, but I hope you take the time to read the entire issue.

—Glenn S. Williams, vice president, group editor, Neurology Reviews

Read more

Read more

Our sixth annual Rare Neurological Disease Special Report is our biggest issue yet. It is very gratifying to know we are part of the rare disease community and witness to some of the exciting developments that are transforming this field. There are many newly approved therapies highlighted in the articles in this issue, as well as brief profiles of a number of research groups within the NIH’s Rare Diseases Clinical Research Network  and an intriguing profile of how the Netflix show Diagnosis used crowdsourcing to solve medical mysteries, many of which involved rare neurologic conditions. That’s just a sampling of what this issue has to offer. There are too many articles to mention each one, but I hope you take the time to read the entire issue.

—Glenn S. Williams, vice president, group editor, Neurology Reviews

Read more

Standards and technology are now available for microbiome profiling to take personalized medicine to the next level, but prospective trials are needed to realize this possibility, according to a leading expert.

The need for prospective microbiomics trials is increasing with the incidence of immune disorders, many of which have been linked with disturbances in the gut, reported Jöel Doré, PhD, at the annual Gut Microbiota for Health World Summit.

“In spite of considerable progress in medicine, together with hygiene, antibiotics, and vaccination developments, we are still seeing an increasing incidence – uncontrolled, that started over 60 years ago – of immune-mediated conditions,” said Dr. Doré, research director at the French National Research Institute for Agriculture, Food, and the Environment.

According to the World Health Organization, one out of four people will be affected by such a disorder in their lifetime, and the incidence rate of some conditions is accelerating faster than others, with geographical distributions that suggest environmental risk factors.

“The rate of incidence of autism in the U.S.A. is a quite scary exponential curve, where less than 1 birth per 5,000 was [affected] in the 1970s, where today it is 1 birth out of 50,” Dr. Doré said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “Prevention is an urgent need, and possibly if we do not manage to understand what’s going on, human longevity might be at stake.”

Multiple studies have shown that transferring microbiota from humans with immune disorders to healthy mice can induce clinical signs of immune disorders, he said. And between humans, fecal transplants from healthy donors have reduced symptoms in patients with conditions such as inflammatory bowel disease.

While these studies support the link between microbe-host relationships and immune function, most of the underlying mechanisms remain unknown, Dr. Doré said. He highlighted the fact that the complex network of interactions involved separates microbiomics research from conventional approaches to disease.

“I want to stress the fact that clinical trials [in the past] have been designed in the situation where infection was the problem, [but] infection is essentially a linear thing; one agent, one risk, one disease,” Dr. Doré said. “What we are dealing with – with the increasing incidence of immune disorders – is host-microbe interaction at the center of everything, and alteration of host-microbe leading to risk, which may lead to disease. But host-microbe interaction is under the control of a vast number of environmental aspects ... so tools to deal with innovation and translation in a totally different or systemic configuration have yet to be invented.”

According to Dr. Doré, to develop clinical applications, research procedures must first be standardized.

“To be of use for the clinician and general practitioner, microbiome profiling will have to rely on pipelines of standardized preanalytical and analytical procedures,” he said. “This starts from sample collection and shipment.”

For the past 5 years, Dr. Doré and colleagues have been working to standardize procedures with a number of organizations around the world, and progress has been made.

“Today we have very good standards for shotgun sequencing,” he said.

With standards solidifying, microbiomics may lead to new clinical strategies for a range of conditions, even beyond immune disorders, Dr. Doré said. He noted that, as a relatively simple measure, gene richness in the microbiome may be used as a health stratifier. Studies have shown that low gene count has been associated with more severe metabolic and inflammatory traits among overweight patients, a lack of response to low-calorie diets among overweight and obese patients, severity of related conditions and risk of mortality among patients with liver cirrhosis, and poorer responses to immunotherapy among patients with cancer.

Certain patterns of flora may be prognostic, Dr. Doré said, citing a study by Gopalakrishnan et al. that involved 112 melanoma patients, in which those with a high abundance of Faecalibacterium had significantly longer progression-free survival than patients with a low abundance of the same bacteria. Further, a multivariate model showed that a high abundance of Faecalibacterium was the strongest predictor of response to immunotherapy, (hazard ratio, 2.95; P = .03), followed closely by prior immunotherapy (HR, 2.87; P = .03). In contrast, patients with a high abundance of Bacteroidales had shorter progression-free survival than patients with a low abundance of the same bacteria.

Dr. Doré also referred to one of the first interventional microbiomics studies in oncology. Mohty et al. conducted the ODYSSEE phase 1b/2a trial involving 25 patients with acute myeloid leukemia, in which patients were given autologous fecal microbiota transplants after induction chemotherapy and antibiotics. The treatment recovered 90% of original microbiota, and the estimated 1-year overall survival rate was 84%, compared with a historical rate of 70%.

The ODYSSEE study serves as proof of concept that microbiomics may eventually offer the next level of personalized medicine, Dr. Doré said. And now, with standards and technology available, researchers can move forward.

Dr. Doré disclosed relationships with BioFortis, Janssen, Sanofi, and other pharmaceutical companies.

Standards and technology are now available for microbiome profiling to take personalized medicine to the next level, but prospective trials are needed to realize this possibility, according to a leading expert.

The need for prospective microbiomics trials is increasing with the incidence of immune disorders, many of which have been linked with disturbances in the gut, reported Jöel Doré, PhD, at the annual Gut Microbiota for Health World Summit.

“In spite of considerable progress in medicine, together with hygiene, antibiotics, and vaccination developments, we are still seeing an increasing incidence – uncontrolled, that started over 60 years ago – of immune-mediated conditions,” said Dr. Doré, research director at the French National Research Institute for Agriculture, Food, and the Environment.

According to the World Health Organization, one out of four people will be affected by such a disorder in their lifetime, and the incidence rate of some conditions is accelerating faster than others, with geographical distributions that suggest environmental risk factors.

“The rate of incidence of autism in the U.S.A. is a quite scary exponential curve, where less than 1 birth per 5,000 was [affected] in the 1970s, where today it is 1 birth out of 50,” Dr. Doré said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “Prevention is an urgent need, and possibly if we do not manage to understand what’s going on, human longevity might be at stake.”

Multiple studies have shown that transferring microbiota from humans with immune disorders to healthy mice can induce clinical signs of immune disorders, he said. And between humans, fecal transplants from healthy donors have reduced symptoms in patients with conditions such as inflammatory bowel disease.

While these studies support the link between microbe-host relationships and immune function, most of the underlying mechanisms remain unknown, Dr. Doré said. He highlighted the fact that the complex network of interactions involved separates microbiomics research from conventional approaches to disease.

“I want to stress the fact that clinical trials [in the past] have been designed in the situation where infection was the problem, [but] infection is essentially a linear thing; one agent, one risk, one disease,” Dr. Doré said. “What we are dealing with – with the increasing incidence of immune disorders – is host-microbe interaction at the center of everything, and alteration of host-microbe leading to risk, which may lead to disease. But host-microbe interaction is under the control of a vast number of environmental aspects ... so tools to deal with innovation and translation in a totally different or systemic configuration have yet to be invented.”

According to Dr. Doré, to develop clinical applications, research procedures must first be standardized.

“To be of use for the clinician and general practitioner, microbiome profiling will have to rely on pipelines of standardized preanalytical and analytical procedures,” he said. “This starts from sample collection and shipment.”

For the past 5 years, Dr. Doré and colleagues have been working to standardize procedures with a number of organizations around the world, and progress has been made.

“Today we have very good standards for shotgun sequencing,” he said.

With standards solidifying, microbiomics may lead to new clinical strategies for a range of conditions, even beyond immune disorders, Dr. Doré said. He noted that, as a relatively simple measure, gene richness in the microbiome may be used as a health stratifier. Studies have shown that low gene count has been associated with more severe metabolic and inflammatory traits among overweight patients, a lack of response to low-calorie diets among overweight and obese patients, severity of related conditions and risk of mortality among patients with liver cirrhosis, and poorer responses to immunotherapy among patients with cancer.

Certain patterns of flora may be prognostic, Dr. Doré said, citing a study by Gopalakrishnan et al. that involved 112 melanoma patients, in which those with a high abundance of Faecalibacterium had significantly longer progression-free survival than patients with a low abundance of the same bacteria. Further, a multivariate model showed that a high abundance of Faecalibacterium was the strongest predictor of response to immunotherapy, (hazard ratio, 2.95; P = .03), followed closely by prior immunotherapy (HR, 2.87; P = .03). In contrast, patients with a high abundance of Bacteroidales had shorter progression-free survival than patients with a low abundance of the same bacteria.

Dr. Doré also referred to one of the first interventional microbiomics studies in oncology. Mohty et al. conducted the ODYSSEE phase 1b/2a trial involving 25 patients with acute myeloid leukemia, in which patients were given autologous fecal microbiota transplants after induction chemotherapy and antibiotics. The treatment recovered 90% of original microbiota, and the estimated 1-year overall survival rate was 84%, compared with a historical rate of 70%.

The ODYSSEE study serves as proof of concept that microbiomics may eventually offer the next level of personalized medicine, Dr. Doré said. And now, with standards and technology available, researchers can move forward.

Dr. Doré disclosed relationships with BioFortis, Janssen, Sanofi, and other pharmaceutical companies.

Standards and technology are now available for microbiome profiling to take personalized medicine to the next level, but prospective trials are needed to realize this possibility, according to a leading expert.

The need for prospective microbiomics trials is increasing with the incidence of immune disorders, many of which have been linked with disturbances in the gut, reported Jöel Doré, PhD, at the annual Gut Microbiota for Health World Summit.

“In spite of considerable progress in medicine, together with hygiene, antibiotics, and vaccination developments, we are still seeing an increasing incidence – uncontrolled, that started over 60 years ago – of immune-mediated conditions,” said Dr. Doré, research director at the French National Research Institute for Agriculture, Food, and the Environment.

According to the World Health Organization, one out of four people will be affected by such a disorder in their lifetime, and the incidence rate of some conditions is accelerating faster than others, with geographical distributions that suggest environmental risk factors.

“The rate of incidence of autism in the U.S.A. is a quite scary exponential curve, where less than 1 birth per 5,000 was [affected] in the 1970s, where today it is 1 birth out of 50,” Dr. Doré said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “Prevention is an urgent need, and possibly if we do not manage to understand what’s going on, human longevity might be at stake.”

Multiple studies have shown that transferring microbiota from humans with immune disorders to healthy mice can induce clinical signs of immune disorders, he said. And between humans, fecal transplants from healthy donors have reduced symptoms in patients with conditions such as inflammatory bowel disease.

While these studies support the link between microbe-host relationships and immune function, most of the underlying mechanisms remain unknown, Dr. Doré said. He highlighted the fact that the complex network of interactions involved separates microbiomics research from conventional approaches to disease.

“I want to stress the fact that clinical trials [in the past] have been designed in the situation where infection was the problem, [but] infection is essentially a linear thing; one agent, one risk, one disease,” Dr. Doré said. “What we are dealing with – with the increasing incidence of immune disorders – is host-microbe interaction at the center of everything, and alteration of host-microbe leading to risk, which may lead to disease. But host-microbe interaction is under the control of a vast number of environmental aspects ... so tools to deal with innovation and translation in a totally different or systemic configuration have yet to be invented.”

According to Dr. Doré, to develop clinical applications, research procedures must first be standardized.

“To be of use for the clinician and general practitioner, microbiome profiling will have to rely on pipelines of standardized preanalytical and analytical procedures,” he said. “This starts from sample collection and shipment.”

For the past 5 years, Dr. Doré and colleagues have been working to standardize procedures with a number of organizations around the world, and progress has been made.

“Today we have very good standards for shotgun sequencing,” he said.

With standards solidifying, microbiomics may lead to new clinical strategies for a range of conditions, even beyond immune disorders, Dr. Doré said. He noted that, as a relatively simple measure, gene richness in the microbiome may be used as a health stratifier. Studies have shown that low gene count has been associated with more severe metabolic and inflammatory traits among overweight patients, a lack of response to low-calorie diets among overweight and obese patients, severity of related conditions and risk of mortality among patients with liver cirrhosis, and poorer responses to immunotherapy among patients with cancer.

Certain patterns of flora may be prognostic, Dr. Doré said, citing a study by Gopalakrishnan et al. that involved 112 melanoma patients, in which those with a high abundance of Faecalibacterium had significantly longer progression-free survival than patients with a low abundance of the same bacteria. Further, a multivariate model showed that a high abundance of Faecalibacterium was the strongest predictor of response to immunotherapy, (hazard ratio, 2.95; P = .03), followed closely by prior immunotherapy (HR, 2.87; P = .03). In contrast, patients with a high abundance of Bacteroidales had shorter progression-free survival than patients with a low abundance of the same bacteria.

Dr. Doré also referred to one of the first interventional microbiomics studies in oncology. Mohty et al. conducted the ODYSSEE phase 1b/2a trial involving 25 patients with acute myeloid leukemia, in which patients were given autologous fecal microbiota transplants after induction chemotherapy and antibiotics. The treatment recovered 90% of original microbiota, and the estimated 1-year overall survival rate was 84%, compared with a historical rate of 70%.

The ODYSSEE study serves as proof of concept that microbiomics may eventually offer the next level of personalized medicine, Dr. Doré said. And now, with standards and technology available, researchers can move forward.

Dr. Doré disclosed relationships with BioFortis, Janssen, Sanofi, and other pharmaceutical companies.