User login
Ulcerative Colitis: Presentation and Diagnosis
Treating homeless patients: Book offers key insights
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
As a psychiatrist dedicated to working with people who are experiencing homelessness, I was very impressed with the new book edited by Col. (Ret.) Elspeth Cameron Ritchie, MD, MPH, and Maria D. Llorente, MD, about treating and providing services to this vulnerable population.
The book, “Clinical Management of the Homeless Patient: Social, Psychiatric, and Medical Issues” (Cham, Switzerland: Springer Nature Switzerland, 2021), offers an in-depth review and analysis of the biopsychosocial complexities that affect how medical and behavioral health conditions present in those who are unhoused. Notably, the book recommends with great sensitivity best practices to address these conditions with care, understanding, and love.
This text, invaluable in particular for those of us clinicians who work with people experiencing homelessness (PEH), provides a historical context of homelessness in the United States, an evaluation of the current state, and indispensable guidance for medical and behavioral health practitioners, case managers, housing navigators, and policy makers alike. It also serves as an inspiring source for those who are considering work in the public sector while reminding those of us in the field why we continue to do this challenging and rewarding work.
Tips can provide hope to clinicians
The volume is divided into four clear sections that are easy to navigate depending on your area of expertise and interest. Each chapter consolidates an extensive literature review into an intriguing and thought-provoking analysis. Part I, “The Big Picture – Social and Medical Issues,” focuses on conditions that disproportionately affect those who are unhoused. The authors offer a glimpse into the unique challenges of managing routine health conditions. They also detail the practical knowledge that’s needed to best care for our most vulnerable neighbors; for example, promoting a shared decision-making model; simplifying treatment plans; prescribing, when possible, medications that are dosed daily – instead of multiple times per day; allowing for walk-in appointments; and addressing cultural, linguistic, and educational barriers.
Most chapters highlight informative case examples that bring the text to life. It can be heartbreaking to recognize and witness the inhumane conditions in which PEH live, and these practical tips and suggestions for future policies based on best practices can help prevent burnout and provide hope for those who care for this community.
Part II, “Psychiatric Issues and Treatments,” presents a brief yet comprehensive history on homelessness, beginning with the deep shame that PEH experienced in Colonial times as the result of cultural and religious influences. Sadly, that negative judgment continues to this day.
The authors also explain how deinstitutionalization and transinstitutionalization have shaped the current state of homelessness, including why many PEH receive their care in emergency departments while incarcerated. This section highlights the barriers of care that are created not just by the patient, but also by the clinicians and systems of care – and what’s needed practically to overcome those challenges.
I appreciate the chapter on substance use disorders. It reminds us that the most commonly used substance among PEH is tobacco, which has serious health effects and for which we have treatment; nevertheless, . This section also provides examples of the trauma-informed language to use when addressing difficult and sometimes stigmatizing topics, such as survival sex and trauma history.
The evidence-based discussion continues in Part III with a focus on topics that everyone working with PEH should understand, including food insecurity, the criminal justice system, and sex trafficking. Part IV highlights best practices that should be replicated in every community, including Housing First approaches, medical respite care, and multiple Veterans Administration programs.
Throughout the text, major themes reverberate across the chapters, beginning with empathy. All who work with PEH must understand the conditions and challenges PEH face every day that affect their physical and mental health. The authors offer a stark and pointed reminder that being unhoused amounts to a full-time job just to meet basic needs. In addition, the devastating role of trauma and structural racism in creating and promoting the conditions that lead someone to be unhoused cannot be underestimated.
Fortunately, the primary aim of the book is to highlight solutions, and it’s here that the book shines. While some interventions are well-known, such as the importance of working in multidisciplinary teams, building trust and rapport with our patients, and urging clinicians and institutions to examine their own judgments and biases that might interfere with humane treatment, other suggestions will lead some readers into new territory. The authors, for example, maintain that we need more data and evidence-based research that include PEH. They also make a case for more preventive care and enhanced professional education for all health care workers that centers on trauma-informed care, social determinants of health, and the unique needs of especially vulnerable communities, such as the unhoused LBGTQ+ community and policies that promote best practices, such as Housing First. The book is a stirring read. It offers both inspiration and practical guidance for all who are currently working with or interested in caring for people experiencing homelessness.
Dr. Bird is a psychiatrist with Alameda County Health Care for the Homeless and the TRUST Clinic in Oakland, Calif. She also is a cofounder of StreetHealth, a backpack street medicine team that provides psychiatric and substance use disorder treatment to people experiencing homelessness in downtown Oakland.
Dr. Bird has no disclosures.
Severe Asthma: Eosinophilic Asthma
What causes cancer? There’s a lot we don’t know
People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?
In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.
But what about the remaining 60% of cancers?
The study suggests that, And a small but significant number may simply be caused by chance.
Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
Possibility 1: Known risk factors contribute more than we realize
For certain factors, a straight line can be drawn to cancer.
Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.
In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.
“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.
For other known risk factors, such as obesity and air pollution, many more questions than answers remain.
Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).
Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.
However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”
A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.
On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.
In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.
When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
Possibility 2: Environmental or lifestyle factors remain under the radar
Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.
One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.
“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”
On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.
“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”
In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.
“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.
Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.
“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
Possibility 3: Some cancers occur by chance
When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.
“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”
But what fraction of cancers are attributable to chance?
A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.
That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.
The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”
Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.
But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.
“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.
The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.
“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”
A version of this article first appeared on Medscape.com.
People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?
In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.
But what about the remaining 60% of cancers?
The study suggests that, And a small but significant number may simply be caused by chance.
Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
Possibility 1: Known risk factors contribute more than we realize
For certain factors, a straight line can be drawn to cancer.
Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.
In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.
“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.
For other known risk factors, such as obesity and air pollution, many more questions than answers remain.
Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).
Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.
However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”
A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.
On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.
In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.
When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
Possibility 2: Environmental or lifestyle factors remain under the radar
Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.
One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.
“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”
On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.
“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”
In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.
“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.
Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.
“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
Possibility 3: Some cancers occur by chance
When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.
“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”
But what fraction of cancers are attributable to chance?
A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.
That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.
The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”
Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.
But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.
“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.
The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.
“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”
A version of this article first appeared on Medscape.com.
People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?
In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.
But what about the remaining 60% of cancers?
The study suggests that, And a small but significant number may simply be caused by chance.
Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
Possibility 1: Known risk factors contribute more than we realize
For certain factors, a straight line can be drawn to cancer.
Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.
In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.
“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.
For other known risk factors, such as obesity and air pollution, many more questions than answers remain.
Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).
Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.
However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”
A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.
On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.
In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.
When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
Possibility 2: Environmental or lifestyle factors remain under the radar
Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.
One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.
“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”
On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.
“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”
In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.
“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.
Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.
“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
Possibility 3: Some cancers occur by chance
When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.
“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”
But what fraction of cancers are attributable to chance?
A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.
That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.
The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”
Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.
But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.
“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.
The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.
“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”
A version of this article first appeared on Medscape.com.
Positive phase 3 topline results for early Parkinson’s drug
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Chicago oncologist charged with insider trading
, according to a Dec. 20 press release issued by the U.S. Department of Justice.
Daniel V.T. Catenacci, MD, PhD, a gastrointestinal medical oncologist and associate professor of medicine at the University of Chicago, is alleged to have used confidential information to purchase shares of California-based biotechnology company Five Prime Therapeutics before it publicly announced positive results from a clinical trial of bemarituzumab, an experimental cancer drug.
Dr. Catenacci served as the lead investigator of the clinical trial that evaluated bemarituzumab. The drug, which earned breakthrough therapy designation from the Food and Drug Administration earlier this year, is designed to target fibroblast growth factor receptor 2b (FGFR2b), overexpressed in about 30% of patients with HER2-negative gastric cancer and other solid tumors.
Bemarituzumab is being positioned as a potential frontline therapy for advanced gastric or gastroesophageal junction cancer. A recent phase 2 trial found that adding bemarituzumab to chemotherapy in this patient population improved survival over chemotherapy alone.
According to the criminal information, filed on Dec. 17 in U.S. District Court in Chicago, the charges state that, in November 2020, Dr. Catenacci “used material, non-public information about the trial results to make more than $134,000 in illegal profits from the purchase and sale of securities in the company.”
More specifically, the SEC’s complaint alleges that Dr. Catenacci received confidential information about the company and its positive clinical trial results through his position as principal investigator. Dr. Catenacci then purchased almost 8,800 shares of Five Prime Therapeutics before the company announced the positive results. Dr. Catenacci subsequently sold those shares shortly after the trial results were announced. In the interim, the shares tripled or quadrupled in value.
He has been charged with one count of securities fraud, punishable by up to 20 years in federal prison. Arraignment in federal court in Chicago has yet to be scheduled.
In addition, the federal complaint alleges that Dr. Catenacci violated the antifraud provisions of the federal securities laws. According to a press release, “Catenacci has agreed to be permanently enjoined from violations of these provisions, and to pay a civil penalty in an amount to be determined by the court later.”
Erin E. Schneider, regional director of the SEC’s San Francisco Regional Office, stated in the press release that clinical drug trials typically involve sensitive and valuable information about the viability of an experimental drug.
“As alleged in our complaint, Catenacci was required to safeguard the material nonpublic information he learned about Five Prime’s clinical trial, and not trade on it,” said Mr. Schneider.
A version of this article first appeared on Medscape.com.
, according to a Dec. 20 press release issued by the U.S. Department of Justice.
Daniel V.T. Catenacci, MD, PhD, a gastrointestinal medical oncologist and associate professor of medicine at the University of Chicago, is alleged to have used confidential information to purchase shares of California-based biotechnology company Five Prime Therapeutics before it publicly announced positive results from a clinical trial of bemarituzumab, an experimental cancer drug.
Dr. Catenacci served as the lead investigator of the clinical trial that evaluated bemarituzumab. The drug, which earned breakthrough therapy designation from the Food and Drug Administration earlier this year, is designed to target fibroblast growth factor receptor 2b (FGFR2b), overexpressed in about 30% of patients with HER2-negative gastric cancer and other solid tumors.
Bemarituzumab is being positioned as a potential frontline therapy for advanced gastric or gastroesophageal junction cancer. A recent phase 2 trial found that adding bemarituzumab to chemotherapy in this patient population improved survival over chemotherapy alone.
According to the criminal information, filed on Dec. 17 in U.S. District Court in Chicago, the charges state that, in November 2020, Dr. Catenacci “used material, non-public information about the trial results to make more than $134,000 in illegal profits from the purchase and sale of securities in the company.”
More specifically, the SEC’s complaint alleges that Dr. Catenacci received confidential information about the company and its positive clinical trial results through his position as principal investigator. Dr. Catenacci then purchased almost 8,800 shares of Five Prime Therapeutics before the company announced the positive results. Dr. Catenacci subsequently sold those shares shortly after the trial results were announced. In the interim, the shares tripled or quadrupled in value.
He has been charged with one count of securities fraud, punishable by up to 20 years in federal prison. Arraignment in federal court in Chicago has yet to be scheduled.
In addition, the federal complaint alleges that Dr. Catenacci violated the antifraud provisions of the federal securities laws. According to a press release, “Catenacci has agreed to be permanently enjoined from violations of these provisions, and to pay a civil penalty in an amount to be determined by the court later.”
Erin E. Schneider, regional director of the SEC’s San Francisco Regional Office, stated in the press release that clinical drug trials typically involve sensitive and valuable information about the viability of an experimental drug.
“As alleged in our complaint, Catenacci was required to safeguard the material nonpublic information he learned about Five Prime’s clinical trial, and not trade on it,” said Mr. Schneider.
A version of this article first appeared on Medscape.com.
, according to a Dec. 20 press release issued by the U.S. Department of Justice.
Daniel V.T. Catenacci, MD, PhD, a gastrointestinal medical oncologist and associate professor of medicine at the University of Chicago, is alleged to have used confidential information to purchase shares of California-based biotechnology company Five Prime Therapeutics before it publicly announced positive results from a clinical trial of bemarituzumab, an experimental cancer drug.
Dr. Catenacci served as the lead investigator of the clinical trial that evaluated bemarituzumab. The drug, which earned breakthrough therapy designation from the Food and Drug Administration earlier this year, is designed to target fibroblast growth factor receptor 2b (FGFR2b), overexpressed in about 30% of patients with HER2-negative gastric cancer and other solid tumors.
Bemarituzumab is being positioned as a potential frontline therapy for advanced gastric or gastroesophageal junction cancer. A recent phase 2 trial found that adding bemarituzumab to chemotherapy in this patient population improved survival over chemotherapy alone.
According to the criminal information, filed on Dec. 17 in U.S. District Court in Chicago, the charges state that, in November 2020, Dr. Catenacci “used material, non-public information about the trial results to make more than $134,000 in illegal profits from the purchase and sale of securities in the company.”
More specifically, the SEC’s complaint alleges that Dr. Catenacci received confidential information about the company and its positive clinical trial results through his position as principal investigator. Dr. Catenacci then purchased almost 8,800 shares of Five Prime Therapeutics before the company announced the positive results. Dr. Catenacci subsequently sold those shares shortly after the trial results were announced. In the interim, the shares tripled or quadrupled in value.
He has been charged with one count of securities fraud, punishable by up to 20 years in federal prison. Arraignment in federal court in Chicago has yet to be scheduled.
In addition, the federal complaint alleges that Dr. Catenacci violated the antifraud provisions of the federal securities laws. According to a press release, “Catenacci has agreed to be permanently enjoined from violations of these provisions, and to pay a civil penalty in an amount to be determined by the court later.”
Erin E. Schneider, regional director of the SEC’s San Francisco Regional Office, stated in the press release that clinical drug trials typically involve sensitive and valuable information about the viability of an experimental drug.
“As alleged in our complaint, Catenacci was required to safeguard the material nonpublic information he learned about Five Prime’s clinical trial, and not trade on it,” said Mr. Schneider.
A version of this article first appeared on Medscape.com.
High-fiber diet may improve melanoma immunotherapy response, outcomes
a new study shows.
Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.
And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.
“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”
Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.
Still, the role diet and probiotic supplements play in treatment response remains poorly understood.
In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.
In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).
Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).
The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.
“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.
When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.
Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”
The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.
According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”
Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.
However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”
While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.
Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.
Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.
This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
a new study shows.
Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.
And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.
“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”
Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.
Still, the role diet and probiotic supplements play in treatment response remains poorly understood.
In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.
In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).
Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).
The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.
“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.
When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.
Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”
The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.
According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”
Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.
However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”
While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.
Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.
Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.
This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
a new study shows.
Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.
And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.
“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”
Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.
Still, the role diet and probiotic supplements play in treatment response remains poorly understood.
In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.
In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).
Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).
The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.
“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.
When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.
Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”
The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.
According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”
Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.
However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”
While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.
Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.
Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.
This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
FROM NATURE
COVID booster protection may wane in about 10 weeks, new data show
, according to new data from Britain.
U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.
“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”
Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.
Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)
Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.
The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.
“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.
The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.
A version of this article first appeared on WebMD.com.
, according to new data from Britain.
U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.
“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”
Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.
Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)
Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.
The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.
“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.
The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.
A version of this article first appeared on WebMD.com.
, according to new data from Britain.
U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.
“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”
Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.
Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)
Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.
The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.
“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.
The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.
A version of this article first appeared on WebMD.com.
SCAMP: Assessing body-focused repetitive behaviors
Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.1
The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation2 describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)
Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al3 described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?
Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors.
Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT.
Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair.
Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.
Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.
1. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
2. The TLC Foundation for Body-Focused Repetitive Behaviors (2016). Expert consensus treatment guidelines. Accessed November 30, 2021. https://www.bfrb.org/storage/documents/Expert_Consensus_Treatment_Guidelines_2016w.pdf
3. Mansueto CS, Vavricheck SM, Golomb RG. Overcoming Body-Focused Repetitive Behaviors: A Comprehensive Behavioral Treatment for Hair Pulling and Skin Picking. New Harbinger Publications; 2019.
Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.1
The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation2 describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)
Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al3 described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?
Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors.
Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT.
Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair.
Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.
Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.
Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.1
The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation2 describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)
Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al3 described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?
Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors.
Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT.
Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair.
Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.
Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.
1. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
2. The TLC Foundation for Body-Focused Repetitive Behaviors (2016). Expert consensus treatment guidelines. Accessed November 30, 2021. https://www.bfrb.org/storage/documents/Expert_Consensus_Treatment_Guidelines_2016w.pdf
3. Mansueto CS, Vavricheck SM, Golomb RG. Overcoming Body-Focused Repetitive Behaviors: A Comprehensive Behavioral Treatment for Hair Pulling and Skin Picking. New Harbinger Publications; 2019.
1. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
2. The TLC Foundation for Body-Focused Repetitive Behaviors (2016). Expert consensus treatment guidelines. Accessed November 30, 2021. https://www.bfrb.org/storage/documents/Expert_Consensus_Treatment_Guidelines_2016w.pdf
3. Mansueto CS, Vavricheck SM, Golomb RG. Overcoming Body-Focused Repetitive Behaviors: A Comprehensive Behavioral Treatment for Hair Pulling and Skin Picking. New Harbinger Publications; 2019.
Spesolimab speeds lesion clearance in generalized pustular psoriasis
GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.
“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.
In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.
The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.
After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).
Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).
In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.
“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.
“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.
The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.
The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.
No FDA-approved therapy
“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”
Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added.
Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”
On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.
The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.
GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.
“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.
In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.
The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.
After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).
Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).
In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.
“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.
“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.
The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.
The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.
No FDA-approved therapy
“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”
Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added.
Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”
On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.
The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.
GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.
“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.
In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.
The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.
After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).
Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).
In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.
“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.
“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.
The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.
The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.
No FDA-approved therapy
“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”
Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added.
Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”
On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.
The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE