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Screening for adolescent substance use; Changing routines during COVID-19
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Love in the time of coronavirus
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Multigene panel testing for colorectal cancer
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Let’s learn from our experience
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief
TERAVOLT data suggest high death rate in lung cancer patients with COVID-19
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM AACR 2020
Reproductive psychiatry during the COVID-19 pandemic
When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.
It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.
For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.
While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.
For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
Planned pregnancy and contraception during the COVID-19 pandemic
Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.
A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
Telemedicine: telepsychiatry and obstetrics virtual visits
While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.
The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.
Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
Recognition and treatment of anxiety in perinatal patients
Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.
These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.
During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.
Miscarriage and infertility
A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.
Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
Sustaining emotional well-being across pregnancy
Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.
Preservation of sleep
Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.
During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.
Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder
Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.
While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).
As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
Virtual rounds in reproductive psychiatry and women’s mental health
The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.
Changes in the postpartum experience
The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.
There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.
I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.
Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.
The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email him at [email protected].
When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.
It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.
For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.
While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.
For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
Planned pregnancy and contraception during the COVID-19 pandemic
Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.
A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
Telemedicine: telepsychiatry and obstetrics virtual visits
While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.
The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.
Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
Recognition and treatment of anxiety in perinatal patients
Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.
These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.
During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.
Miscarriage and infertility
A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.
Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
Sustaining emotional well-being across pregnancy
Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.
Preservation of sleep
Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.
During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.
Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder
Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.
While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).
As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
Virtual rounds in reproductive psychiatry and women’s mental health
The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.
Changes in the postpartum experience
The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.
There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.
I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.
Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.
The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email him at [email protected].
When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.
It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.
For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.
While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.
For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
Planned pregnancy and contraception during the COVID-19 pandemic
Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.
A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
Telemedicine: telepsychiatry and obstetrics virtual visits
While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.
The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.
Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
Recognition and treatment of anxiety in perinatal patients
Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.
These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.
During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.
Miscarriage and infertility
A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.
Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
Sustaining emotional well-being across pregnancy
Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.
Preservation of sleep
Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.
During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.
Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder
Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.
While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).
As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
Virtual rounds in reproductive psychiatry and women’s mental health
The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.
Changes in the postpartum experience
The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.
There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.
I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.
Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.
The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email him at [email protected].
A pandemic of pediatric panic
Seventy-three. That is the average number of questions asked daily by preschool-aged children.
Children ask questions to make sense of their world, to learn how things work, to verify their safety, and to interact with others. As a physician, a child and adolescent psychiatrist, and a father to 6-year-old twin daughters, I too am asking more questions these days. Both professionally and personally, these questions are prompted by shifts in routines, uncertainty, and anxiety brought on by the ongoing coronavirus disease 2019 (COVID-19) pandemic. In parallel, I find myself reflecting on my twin daughters’ questions; their questions reverberate with my own, and with the increased anxiety and fears of my patients and their parents.
With this in mind, I’d like to share 2 questions related to pediatric anxiety that may sculpt our clinical work—whether with children, adolescents, or adults—as we provide treatment and comfort to our patients during this pandemic of anxiety.
How do parents affect children’s anxiety?
First, children take cues from their parents. Almost a half century ago, child and adolescent psychiatrist Robert Emde, MD, and others, using elegantly designed experimental settings, documented that a mother’s response strongly influences her young son or daughter’s emotional reaction to a stranger, or to new situations.1 Specifically, very young children were less afraid and interacted more with a stranger and did so more quickly when their mother had a positive (as opposed to neutral or fearful) reaction to the situation.2 Further, in these studies, when the parent’s face was partially covered, very young children became more fearful. Taken together, these findings remind us that children actively seek to read the affective states of those who care for them, and use these reactions to anchor their responses to shifts in routine, such as those brought on by the ongoing COVID-19 pandemic.
Second, in reacting to the pandemic, parents model emotional regulation—an important skill that children and adolescents must develop as they experience intense affect and anxiety. As mental health clinicians, we know that emotional regulation is an essential component of mental health, and problems with it are a hallmark characteristic of several disorders, including anxiety disorders. Further, neuroimaging studies over the past decade have demonstrated that the way in which the medial prefrontal cortex and lower limbic structures (eg, the amygdala) are connected shifts from early childhood through adolescence and into early adulthood.3 It is likely that these shifts in functional connectivity are shaped by the environment as well as intrinsic aspects of the patient’s biology, and that these shifts subtend the developmental expression of anxiety, particularly in times of stress.
How should we talk to children about the pandemic?
Trust is not only the scaffold of our therapeutic relationships, but also a critical component of our conversations with children about the pandemic. Having established a trusting relationship prior to talking with children about their anxiety and about the pandemic, we will do well to remember that there is often more to a question than the actual direct interrogative. From a developmental standpoint, children may repeatedly ask the same question because they are struggling to understand an abstract concept, or are unable to make the same implicit causal link that we—as adults—have made. Also, children may ask the same question multiple times as a way of seeking reassurance. Finally, when a child asks her father “How many people are going to die?” she may actually be asking whether her parents, grandparents, or friends will be safe and healthy. Thus, as we talk with children, we must remember that they may be implicitly asking for more than a number, date, or mechanism. We must think about the motivation for their questions vis a vis their specific fears and past experiences.
For children, adolescents, and adults, the anxiety created by the pandemic constantly shifts, is hard-to-define, and pervades their lives. This ensuing chronic variable stress can worsen both physical and mental health.4 But, it also creates an opportunity for resiliency which—like the coronavirus—can be contagious.5,6 Knowing this, I’d like to ask 4 questions, based on David Brooks’ recent Op-Ed in the New York Times7:
- Can we become “softer and wiser” as a result of the pandemic?
- How can we inoculate our patients against the loneliness and isolation that worsen most psychiatric disorders?
- How can we “see deeper into [our]selves” to provide comfort to our patients, families, and each other as we confront this viral pandemic of anxiety?
- Following “social distancing,” how do we rekindle “social trust”?
1. Emde RN, Gaensbauer TJ, Harmon RJ. Emotional expression in infancy; a biobehavioral study. Psychol Issues. 1976;10(01):1-200.
2. Feinman S, Lewis M. Social referencing at ten months: a second-order effect on infants’ responses to strangers. Child Dev. 1983;54(4):878-887.
3. Gee DG, Gabard-Durnam LJ, Flannery J, et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci U S A. 2013;110(39):15638-15643.
4. Keeshin BR, Cronholm PF, Strawn JR. Physiologic changes associated with violence and abuse exposure: an examination of related medical conditions. Trauma Violence Abuse. 2012;13(1):41-56.
5. Malhi GS, Das P, Bell E, et al. Modelling resilience in adolescence and adversity: a novel framework to inform research and practice. Transl Psychiatry. 2019;9(1):316. doi: 10.1038/s41398-019-0651-y.
6. Rutter M. Annual Research Review: resilience--clinical implications. J Child Psychol Psychiatry. 2013;54(4):474-487.
7. Brooks D. The pandemic of fear and agony. New York Times. April 9, 2020. https://www.nytimes.com/2020/04/09/opinion/covid-anxiety.html. Accessed April 14, 2020.
Seventy-three. That is the average number of questions asked daily by preschool-aged children.
Children ask questions to make sense of their world, to learn how things work, to verify their safety, and to interact with others. As a physician, a child and adolescent psychiatrist, and a father to 6-year-old twin daughters, I too am asking more questions these days. Both professionally and personally, these questions are prompted by shifts in routines, uncertainty, and anxiety brought on by the ongoing coronavirus disease 2019 (COVID-19) pandemic. In parallel, I find myself reflecting on my twin daughters’ questions; their questions reverberate with my own, and with the increased anxiety and fears of my patients and their parents.
With this in mind, I’d like to share 2 questions related to pediatric anxiety that may sculpt our clinical work—whether with children, adolescents, or adults—as we provide treatment and comfort to our patients during this pandemic of anxiety.
How do parents affect children’s anxiety?
First, children take cues from their parents. Almost a half century ago, child and adolescent psychiatrist Robert Emde, MD, and others, using elegantly designed experimental settings, documented that a mother’s response strongly influences her young son or daughter’s emotional reaction to a stranger, or to new situations.1 Specifically, very young children were less afraid and interacted more with a stranger and did so more quickly when their mother had a positive (as opposed to neutral or fearful) reaction to the situation.2 Further, in these studies, when the parent’s face was partially covered, very young children became more fearful. Taken together, these findings remind us that children actively seek to read the affective states of those who care for them, and use these reactions to anchor their responses to shifts in routine, such as those brought on by the ongoing COVID-19 pandemic.
Second, in reacting to the pandemic, parents model emotional regulation—an important skill that children and adolescents must develop as they experience intense affect and anxiety. As mental health clinicians, we know that emotional regulation is an essential component of mental health, and problems with it are a hallmark characteristic of several disorders, including anxiety disorders. Further, neuroimaging studies over the past decade have demonstrated that the way in which the medial prefrontal cortex and lower limbic structures (eg, the amygdala) are connected shifts from early childhood through adolescence and into early adulthood.3 It is likely that these shifts in functional connectivity are shaped by the environment as well as intrinsic aspects of the patient’s biology, and that these shifts subtend the developmental expression of anxiety, particularly in times of stress.
How should we talk to children about the pandemic?
Trust is not only the scaffold of our therapeutic relationships, but also a critical component of our conversations with children about the pandemic. Having established a trusting relationship prior to talking with children about their anxiety and about the pandemic, we will do well to remember that there is often more to a question than the actual direct interrogative. From a developmental standpoint, children may repeatedly ask the same question because they are struggling to understand an abstract concept, or are unable to make the same implicit causal link that we—as adults—have made. Also, children may ask the same question multiple times as a way of seeking reassurance. Finally, when a child asks her father “How many people are going to die?” she may actually be asking whether her parents, grandparents, or friends will be safe and healthy. Thus, as we talk with children, we must remember that they may be implicitly asking for more than a number, date, or mechanism. We must think about the motivation for their questions vis a vis their specific fears and past experiences.
For children, adolescents, and adults, the anxiety created by the pandemic constantly shifts, is hard-to-define, and pervades their lives. This ensuing chronic variable stress can worsen both physical and mental health.4 But, it also creates an opportunity for resiliency which—like the coronavirus—can be contagious.5,6 Knowing this, I’d like to ask 4 questions, based on David Brooks’ recent Op-Ed in the New York Times7:
- Can we become “softer and wiser” as a result of the pandemic?
- How can we inoculate our patients against the loneliness and isolation that worsen most psychiatric disorders?
- How can we “see deeper into [our]selves” to provide comfort to our patients, families, and each other as we confront this viral pandemic of anxiety?
- Following “social distancing,” how do we rekindle “social trust”?
Seventy-three. That is the average number of questions asked daily by preschool-aged children.
Children ask questions to make sense of their world, to learn how things work, to verify their safety, and to interact with others. As a physician, a child and adolescent psychiatrist, and a father to 6-year-old twin daughters, I too am asking more questions these days. Both professionally and personally, these questions are prompted by shifts in routines, uncertainty, and anxiety brought on by the ongoing coronavirus disease 2019 (COVID-19) pandemic. In parallel, I find myself reflecting on my twin daughters’ questions; their questions reverberate with my own, and with the increased anxiety and fears of my patients and their parents.
With this in mind, I’d like to share 2 questions related to pediatric anxiety that may sculpt our clinical work—whether with children, adolescents, or adults—as we provide treatment and comfort to our patients during this pandemic of anxiety.
How do parents affect children’s anxiety?
First, children take cues from their parents. Almost a half century ago, child and adolescent psychiatrist Robert Emde, MD, and others, using elegantly designed experimental settings, documented that a mother’s response strongly influences her young son or daughter’s emotional reaction to a stranger, or to new situations.1 Specifically, very young children were less afraid and interacted more with a stranger and did so more quickly when their mother had a positive (as opposed to neutral or fearful) reaction to the situation.2 Further, in these studies, when the parent’s face was partially covered, very young children became more fearful. Taken together, these findings remind us that children actively seek to read the affective states of those who care for them, and use these reactions to anchor their responses to shifts in routine, such as those brought on by the ongoing COVID-19 pandemic.
Second, in reacting to the pandemic, parents model emotional regulation—an important skill that children and adolescents must develop as they experience intense affect and anxiety. As mental health clinicians, we know that emotional regulation is an essential component of mental health, and problems with it are a hallmark characteristic of several disorders, including anxiety disorders. Further, neuroimaging studies over the past decade have demonstrated that the way in which the medial prefrontal cortex and lower limbic structures (eg, the amygdala) are connected shifts from early childhood through adolescence and into early adulthood.3 It is likely that these shifts in functional connectivity are shaped by the environment as well as intrinsic aspects of the patient’s biology, and that these shifts subtend the developmental expression of anxiety, particularly in times of stress.
How should we talk to children about the pandemic?
Trust is not only the scaffold of our therapeutic relationships, but also a critical component of our conversations with children about the pandemic. Having established a trusting relationship prior to talking with children about their anxiety and about the pandemic, we will do well to remember that there is often more to a question than the actual direct interrogative. From a developmental standpoint, children may repeatedly ask the same question because they are struggling to understand an abstract concept, or are unable to make the same implicit causal link that we—as adults—have made. Also, children may ask the same question multiple times as a way of seeking reassurance. Finally, when a child asks her father “How many people are going to die?” she may actually be asking whether her parents, grandparents, or friends will be safe and healthy. Thus, as we talk with children, we must remember that they may be implicitly asking for more than a number, date, or mechanism. We must think about the motivation for their questions vis a vis their specific fears and past experiences.
For children, adolescents, and adults, the anxiety created by the pandemic constantly shifts, is hard-to-define, and pervades their lives. This ensuing chronic variable stress can worsen both physical and mental health.4 But, it also creates an opportunity for resiliency which—like the coronavirus—can be contagious.5,6 Knowing this, I’d like to ask 4 questions, based on David Brooks’ recent Op-Ed in the New York Times7:
- Can we become “softer and wiser” as a result of the pandemic?
- How can we inoculate our patients against the loneliness and isolation that worsen most psychiatric disorders?
- How can we “see deeper into [our]selves” to provide comfort to our patients, families, and each other as we confront this viral pandemic of anxiety?
- Following “social distancing,” how do we rekindle “social trust”?
1. Emde RN, Gaensbauer TJ, Harmon RJ. Emotional expression in infancy; a biobehavioral study. Psychol Issues. 1976;10(01):1-200.
2. Feinman S, Lewis M. Social referencing at ten months: a second-order effect on infants’ responses to strangers. Child Dev. 1983;54(4):878-887.
3. Gee DG, Gabard-Durnam LJ, Flannery J, et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci U S A. 2013;110(39):15638-15643.
4. Keeshin BR, Cronholm PF, Strawn JR. Physiologic changes associated with violence and abuse exposure: an examination of related medical conditions. Trauma Violence Abuse. 2012;13(1):41-56.
5. Malhi GS, Das P, Bell E, et al. Modelling resilience in adolescence and adversity: a novel framework to inform research and practice. Transl Psychiatry. 2019;9(1):316. doi: 10.1038/s41398-019-0651-y.
6. Rutter M. Annual Research Review: resilience--clinical implications. J Child Psychol Psychiatry. 2013;54(4):474-487.
7. Brooks D. The pandemic of fear and agony. New York Times. April 9, 2020. https://www.nytimes.com/2020/04/09/opinion/covid-anxiety.html. Accessed April 14, 2020.
1. Emde RN, Gaensbauer TJ, Harmon RJ. Emotional expression in infancy; a biobehavioral study. Psychol Issues. 1976;10(01):1-200.
2. Feinman S, Lewis M. Social referencing at ten months: a second-order effect on infants’ responses to strangers. Child Dev. 1983;54(4):878-887.
3. Gee DG, Gabard-Durnam LJ, Flannery J, et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci U S A. 2013;110(39):15638-15643.
4. Keeshin BR, Cronholm PF, Strawn JR. Physiologic changes associated with violence and abuse exposure: an examination of related medical conditions. Trauma Violence Abuse. 2012;13(1):41-56.
5. Malhi GS, Das P, Bell E, et al. Modelling resilience in adolescence and adversity: a novel framework to inform research and practice. Transl Psychiatry. 2019;9(1):316. doi: 10.1038/s41398-019-0651-y.
6. Rutter M. Annual Research Review: resilience--clinical implications. J Child Psychol Psychiatry. 2013;54(4):474-487.
7. Brooks D. The pandemic of fear and agony. New York Times. April 9, 2020. https://www.nytimes.com/2020/04/09/opinion/covid-anxiety.html. Accessed April 14, 2020.
ESMO gets creative with guidelines for breast cancer care in the COVID-19 era
Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.
ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.
As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.
High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.
Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.
Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
Personalized care and high-priority situations
ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.
The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.
ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.
Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.
Modifications to consider
ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.
For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.
In the metastatic setting, ESMO advises providers to consider:
- Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
- Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
- Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.
ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).
The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
Lower-priority situations
ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.
Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.
ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
Bottom line
The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.
The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.
ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.
As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.
High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.
Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.
Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
Personalized care and high-priority situations
ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.
The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.
ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.
Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.
Modifications to consider
ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.
For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.
In the metastatic setting, ESMO advises providers to consider:
- Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
- Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
- Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.
ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).
The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
Lower-priority situations
ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.
Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.
ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
Bottom line
The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.
The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Like other agencies, the European Society for Medical Oncology has developed guidelines for managing breast cancer patients during the COVID-19 pandemic, recommending when care should be prioritized, delayed, or modified.
ESMO’s breast cancer guidelines expand upon guidelines issued by other groups, addressing a broad spectrum of patient profiles and providing a creative array of treatment options in COVID-19–era clinical practice.
As with ESMO’s other disease-focused COVID-19 guidelines, the breast cancer guidelines are organized by priority levels – high, medium, and low – which are applied to several domains of diagnosis and treatment.
High-priority recommendations apply to patients whose condition is either clinically unstable or whose cancer burden is immediately life-threatening.
Medium-priority recommendations apply to patients for whom delaying care beyond 6 weeks would probably lower the likelihood of a significant benefit from the intervention.
Low-priority recommendations apply to patients for whom services can be delayed for the duration of the COVID-19 pandemic.
Personalized care and high-priority situations
ESMO’s guidelines suggest that multidisciplinary tumor boards should guide decisions about the urgency of care for individual patients, given the complexity of breast cancer biology, the multiplicity of evidence-based treatments, and the possibility of cure or durable high-quality remissions.
The guidelines deliver a clear message that prepandemic discussions about delivering personalized care are even more important now.
ESMO prioritizes investigating high-risk screening mammography results (i.e., BIRADS 5), lumps noted on breast self-examination, clinical evidence of local-regional recurrence, and breast cancer in pregnant women.
Making these scenarios “high priority” will facilitate the best long-term outcomes in time-sensitive scenarios and improve patient satisfaction with care.
Modifications to consider
ESMO provides explicit options for treatment of common breast cancer profiles in which short-term modifications of standard management strategies can safely be considered. Given the generally long natural history of most breast cancer subtypes, these temporary modifications are unlikely to compromise long-term outcomes.
For patients with a new diagnosis of localized breast cancer, the guidelines recommend neoadjuvant chemotherapy, targeted therapy, or hormonal therapy to achieve optimal breast cancer outcomes and safely delay surgery or radiotherapy.
In the metastatic setting, ESMO advises providers to consider:
- Symptom-oriented testing, recognizing the arguable benefit of frequent imaging or serum tumor marker measurement (J Clin Oncol. 2016 Aug 20;34[24]:2820-6).
- Drug holidays, de-escalated maintenance therapy, and protracted schedules of bone-modifying agents.
- Avoiding mTOR and PI3KCA inhibitors as an addition to standard hormonal therapy because of pneumonitis, hyperglycemia, and immunosuppression risks. The guidelines suggest careful thought about adding CDK4/6 inhibitors to standard hormonal therapy because of the added burden of remote safety monitoring with the biologic agents.
ESMO makes suggestions about trimming the duration of adjuvant trastuzumab to 6 months, as in the PERSEPHONE study (Lancet. 2019 Jun 29;393[10191]:2599-612), and modifying the schedule of luteinizing hormone–releasing hormone agonist administration, in an effort to reduce patient exposure to health care personnel (and vice versa).
The guidelines recommend continuing clinical trials if benefits to patients outweigh risks and trials can be modified to enhance patient safety while preserving study endpoint evaluations.
Lower-priority situations
ESMO pointedly assigns a low priority to follow-up of patients who are at high risk of relapse but lack signs or symptoms of relapse.
Like other groups, ESMO recommends that patients with equivocal (i.e., BIRADS 3) screening mammograms should have 6-month follow-up imaging in preference to immediate core needle biopsy of the area(s) of concern.
ESMO uses age to assign priority for postponing adjuvant breast radiation in patients with low- to moderate-risk lesions. However, the guidelines stop surprisingly short of recommending that adjuvant radiation be withheld for older patients with low-risk, stage I, hormonally sensitive, HER2-negative breast cancers who receive endocrine therapy.
Bottom line
The pragmatic adjustments ESMO suggests address the challenges of evaluating and treating breast cancer patients during the COVID-19 pandemic. The guidelines protect each patient’s right to care and safety as well as protecting the safety of caregivers.
The guidelines will likely heighten patients’ satisfaction with care and decrease concern about adequacy of timely evaluation and treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Changing habits, sleep patterns, and home duties during the pandemic
Like you, I’m not sure when this weird Twilight Zone world of coronavirus will end. Even when it does, its effects will be with us for a long time to come.
But in some ways, they may be for the better. Hopefully some of these changes will stick. Like every new situation, I try to take away something of value from it.
As pithy as it sounds, I used to obsess (sort of) over the daily mail delivery. My secretary would check it mid-afternoon, and if it wasn’t there either she or I would run down again before we left. If it still wasn’t there I’d swing by the box when I came in early the next morning. On Saturdays, I’d sometimes drive in just to get the mail.
There certainly are things that come in that are important: payments, bills, medical records, legal cases to review ... but realistically a lot of mail is junk. Office-supply catalogs, CME or pharmaceutical ads, credit card promotions, and so on.
Now? I just don’t care. If I go several days without seeing patients at the office, the mail is at the back of my mind. It’s in a locked box and isn’t going anywhere. Why worry about it? Next time I’m there I can deal with it. It’s not worth thinking about, it’s just the mail. It’s not worth a special trip.
Sleep is another thing. For years my internal alarm has had me up around 4:00 a.m. (I don’t even bother to set one on my phone), and I get up and go in to get started on the day.
Now? I don’t think I’ve ever slept this much. If I have to go to my office, I’m much less rushed. Many days I don’t even have to do that. I walk down to my home office, call up my charts and the day’s video appointment schedule, and we’re off. Granted, once things return to speed, this will probably be back to normal.
My kids are all home from college, so I have the extra time at home to enjoy them and our dogs. My wife, an oncology infusion nurse, doesn’t get home until 6:00 each night, so for now I’ve become a stay-at-home dad. This is actually something I’ve always liked (in high school, I was voted “most likely to to be a house husband”). So I do the laundry and am in charge of dinner each night. I’m enjoying the last, as I get to pick things out, go through recipes, and cook. I won’t say I’m a great cook, but I’m learning and having fun. As strange as it sounds, being a house husband has always been something I wanted to do, so I’m appreciating the opportunity while it lasts.
I think all of us have come to accept this strange pause button that’s been pushed, and I’ll try to learn what I can from it and take that with me as I move forward.
Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.
Like you, I’m not sure when this weird Twilight Zone world of coronavirus will end. Even when it does, its effects will be with us for a long time to come.
But in some ways, they may be for the better. Hopefully some of these changes will stick. Like every new situation, I try to take away something of value from it.
As pithy as it sounds, I used to obsess (sort of) over the daily mail delivery. My secretary would check it mid-afternoon, and if it wasn’t there either she or I would run down again before we left. If it still wasn’t there I’d swing by the box when I came in early the next morning. On Saturdays, I’d sometimes drive in just to get the mail.
There certainly are things that come in that are important: payments, bills, medical records, legal cases to review ... but realistically a lot of mail is junk. Office-supply catalogs, CME or pharmaceutical ads, credit card promotions, and so on.
Now? I just don’t care. If I go several days without seeing patients at the office, the mail is at the back of my mind. It’s in a locked box and isn’t going anywhere. Why worry about it? Next time I’m there I can deal with it. It’s not worth thinking about, it’s just the mail. It’s not worth a special trip.
Sleep is another thing. For years my internal alarm has had me up around 4:00 a.m. (I don’t even bother to set one on my phone), and I get up and go in to get started on the day.
Now? I don’t think I’ve ever slept this much. If I have to go to my office, I’m much less rushed. Many days I don’t even have to do that. I walk down to my home office, call up my charts and the day’s video appointment schedule, and we’re off. Granted, once things return to speed, this will probably be back to normal.
My kids are all home from college, so I have the extra time at home to enjoy them and our dogs. My wife, an oncology infusion nurse, doesn’t get home until 6:00 each night, so for now I’ve become a stay-at-home dad. This is actually something I’ve always liked (in high school, I was voted “most likely to to be a house husband”). So I do the laundry and am in charge of dinner each night. I’m enjoying the last, as I get to pick things out, go through recipes, and cook. I won’t say I’m a great cook, but I’m learning and having fun. As strange as it sounds, being a house husband has always been something I wanted to do, so I’m appreciating the opportunity while it lasts.
I think all of us have come to accept this strange pause button that’s been pushed, and I’ll try to learn what I can from it and take that with me as I move forward.
Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.
Like you, I’m not sure when this weird Twilight Zone world of coronavirus will end. Even when it does, its effects will be with us for a long time to come.
But in some ways, they may be for the better. Hopefully some of these changes will stick. Like every new situation, I try to take away something of value from it.
As pithy as it sounds, I used to obsess (sort of) over the daily mail delivery. My secretary would check it mid-afternoon, and if it wasn’t there either she or I would run down again before we left. If it still wasn’t there I’d swing by the box when I came in early the next morning. On Saturdays, I’d sometimes drive in just to get the mail.
There certainly are things that come in that are important: payments, bills, medical records, legal cases to review ... but realistically a lot of mail is junk. Office-supply catalogs, CME or pharmaceutical ads, credit card promotions, and so on.
Now? I just don’t care. If I go several days without seeing patients at the office, the mail is at the back of my mind. It’s in a locked box and isn’t going anywhere. Why worry about it? Next time I’m there I can deal with it. It’s not worth thinking about, it’s just the mail. It’s not worth a special trip.
Sleep is another thing. For years my internal alarm has had me up around 4:00 a.m. (I don’t even bother to set one on my phone), and I get up and go in to get started on the day.
Now? I don’t think I’ve ever slept this much. If I have to go to my office, I’m much less rushed. Many days I don’t even have to do that. I walk down to my home office, call up my charts and the day’s video appointment schedule, and we’re off. Granted, once things return to speed, this will probably be back to normal.
My kids are all home from college, so I have the extra time at home to enjoy them and our dogs. My wife, an oncology infusion nurse, doesn’t get home until 6:00 each night, so for now I’ve become a stay-at-home dad. This is actually something I’ve always liked (in high school, I was voted “most likely to to be a house husband”). So I do the laundry and am in charge of dinner each night. I’m enjoying the last, as I get to pick things out, go through recipes, and cook. I won’t say I’m a great cook, but I’m learning and having fun. As strange as it sounds, being a house husband has always been something I wanted to do, so I’m appreciating the opportunity while it lasts.
I think all of us have come to accept this strange pause button that’s been pushed, and I’ll try to learn what I can from it and take that with me as I move forward.
Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.
Decreased fetal movement: Time to educate patients and ourselves
We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.
The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.1 We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.2 Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.3 Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,4 which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.
We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.
Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”
Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.5 We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.
The education about and plan for management of decreased fetal movement are two components of the UK Saving Babies Lives Protocol; one study in the United Kingdom has shown a 20% decline in stillbirths from 2010 to 2017. The other two components are making sure to catch all fetal growth restricted babies and smoking cessation. We incorporated this protocol in my practice several months ago, and we have had very positive feedback from patients. We are not getting an increase in concerns/visits and have not had any patients call and say that they were upset about receiving this education. The Word Health Organization calls stillbirth a “neglected tragedy.” The United States has the lowest annual reduction of its stillbirth rate for all high-income nations in the Lancet 2015 series on stillbirth.6
Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
References
1. The Lancet. 2016, Jan 18;387(10018):587-603.
2. JAMA. 2011 Dec 14;306(22):2469-79.
3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.
4. BMJ Open. 2018 Jul 6;8(7):e020031.
5. Midwifery. 2018 Jul;62:171-6.
6. The Lancet. 2016, Jan 18;387(10019):691-702.
*This article was updated on 5/4/2020.
We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.
The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.1 We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.2 Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.3 Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,4 which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.
We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.
Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”
Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.5 We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.
The education about and plan for management of decreased fetal movement are two components of the UK Saving Babies Lives Protocol; one study in the United Kingdom has shown a 20% decline in stillbirths from 2010 to 2017. The other two components are making sure to catch all fetal growth restricted babies and smoking cessation. We incorporated this protocol in my practice several months ago, and we have had very positive feedback from patients. We are not getting an increase in concerns/visits and have not had any patients call and say that they were upset about receiving this education. The Word Health Organization calls stillbirth a “neglected tragedy.” The United States has the lowest annual reduction of its stillbirth rate for all high-income nations in the Lancet 2015 series on stillbirth.6
Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
References
1. The Lancet. 2016, Jan 18;387(10018):587-603.
2. JAMA. 2011 Dec 14;306(22):2469-79.
3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.
4. BMJ Open. 2018 Jul 6;8(7):e020031.
5. Midwifery. 2018 Jul;62:171-6.
6. The Lancet. 2016, Jan 18;387(10019):691-702.
*This article was updated on 5/4/2020.
We have all as providers experienced the tragic stillbirth of a term fetus for one of our patients. Too often no fetal movement was felt for days, but the patient never called. Or the patient did call, but the nonstress test (NST) was reactive or the ultrasound showed normal growth and fluid or the biophysical profile (BPP) was 8/8. Yet the patient still presented with a stillborn fetus a day later. Was the first patient simply so fearful of the likely deceased child within her that she did not call? Or did she simply not know to report it because she was not educated about what decreased fetal movement could mean? Could the second example have been prevented even though the testing was normal? I believe both scenarios could have been prevented with better education for both providers and patients.
The national stillbirth rate has remained relatively stagnant since 2000, despite many improvements in guidelines for the management of higher risk pregnancies.1 We follow the growth of these pregnancies, do NSTs, and often induce these patients prior to the due date. We do this in the hope of having a healthy mom and baby. However, an analysis of 614 stillbirth cases and 1,816 control deliveries found that 81% of patients presenting with a stillborn baby had no risks factors that required additional monitoring.2 Nearly 66% of 1,714 patients with a late stillbirth reported decreased fetal movement, no fetal movement, or a concerning increase in fetal movement in the days leading up to their baby’s death.3 Studies have suggested that persistent decreased fetal movement has an odds ratio for stillbirth of 4.51,4 which is higher than hypertensive disease and diabetes for this same outcome by nearly a factor of two. Yet there are no formal guidelines on education for patients or management of this chief complaint.
We assess fetal movement at every prenatal visit but patients who experienced stillbirth will say they didn’t know why. This is because as a culture and a profession we are afraid to talk about such a taboo subject as stillbirth. We are afraid we will scare our patients if we tell them that a decrease in fetal movement or no fetal movement may be because their baby is at risk for this dreaded complication. On one level this argument makes sense, but as soon as the baby is born we give parents plenty of education and advice to keep their children safe. Telling a parent to remove all bedding, put their baby on their back, and keep their baby from being too warm to prevent sudden infant death syndrome (SIDS) is very scary. However, this education is necessary. If moms simply know the reason why we ask about fetal movements, they may not wait 2 days before they call. We must have faith that pregnant women can handle this education about decreased fetal movement.
Next most important is our response to the complaint of decreased fetal movement. Often when the NST is reactive or the ultrasound is normal, we assume the baby is at no risk and we reassure the mother that everything is fine. We often tell moms the false myth that babies slow down at the end or advise kick counts after this complaint despite studies failing to show their utility. Because the education about kick count is frequency is what matters, a mother may not call if there is a change in pattern or strength – even if she is very worried about this. A baby may “pass” a kick count, but a mom still may be very worried, yet she will not call because the baby “passed.”
Protocols from the United Kingdom and Australia focus on the assumption that the complaint of decreased fetal movement may be the only warning sign of impending stillbirth. Harvey Kliman, MD, PhD, director of reproductive and placental research unit at Yale University, New Haven, Conn. said an analogy to this is a car driving 55 miles per hour despite only 10 miles of gas being left in the tank.* The car is running fine even when it is almost out of gas. That may be why we all have seen a fetus with recent reassuring tests in the last few days who presents stillborn. Perhaps the only warning sign is decreased fetal movement – not a nonreactive NST or low score BPP. Placental insufficiency is often the cause of initially unexplained stillbirth, far more common than “cord accidents.” If we liken the placenta to the “gas tank” for the pregnancy, then decreased fetal movement may be the “low gas” signal on the dashboard. After this patient has a reactive NST and/or reassuring ultrasound, we need to ask her if she is reassured. Data from a study of 380 women found that women who had a gut instinct that something was wrong were 23 times more likely to experience a stillbirth, according to the unadjusted odds ratio from the logistic regression model.5 We should follow up closely with moms who are not reassured and consider induction if they are over 39 weeks. We should tell every mom who presents with a concern about fetal movement that she did the right thing, and we want to hear from her again immediately if the movement is decreased again or persists. We cannot make women feel silly for calling. We should do an ultrasound for worried moms even if the NST is reactive to make sure we are not missing oligohydramnios or fetal growth restriction; the latter is the biggest known risk factor for stillbirth. We also should perform an ultrasound for moms with risk factors for stillbirth such as advanced maternal age or black race.
The education about and plan for management of decreased fetal movement are two components of the UK Saving Babies Lives Protocol; one study in the United Kingdom has shown a 20% decline in stillbirths from 2010 to 2017. The other two components are making sure to catch all fetal growth restricted babies and smoking cessation. We incorporated this protocol in my practice several months ago, and we have had very positive feedback from patients. We are not getting an increase in concerns/visits and have not had any patients call and say that they were upset about receiving this education. The Word Health Organization calls stillbirth a “neglected tragedy.” The United States has the lowest annual reduction of its stillbirth rate for all high-income nations in the Lancet 2015 series on stillbirth.6
Dr. Florescue is an ob.gyn. in private practice at Women Gynecology and Childbirth Associates in Rochester, N.Y. She delivers babies at Highland Hospital in Rochester. She has no relevant financial disclosures.
References
1. The Lancet. 2016, Jan 18;387(10018):587-603.
2. JAMA. 2011 Dec 14;306(22):2469-79.
3. BMC Pregnancy Childbirth. 2015 Aug 15;15:172.
4. BMJ Open. 2018 Jul 6;8(7):e020031.
5. Midwifery. 2018 Jul;62:171-6.
6. The Lancet. 2016, Jan 18;387(10019):691-702.
*This article was updated on 5/4/2020.