Opinion

 

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

 

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

 

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

You learned a lot of things in medical school. But there must have been some things that you unlearned on the way to your degree. For instance, you unlearned that you could catch a cold by playing outside on a cold damp day without your jacket. You unlearned that handling a toad would give you warts.

©KatarzynaBialasiewicz/Thinkstock

The authors of a recent study suggest that over your 4 years in medical school you also unlearned how to be empathetic (“Does Empathy Decline in the Clinical Phase of Medical Education? A Nationwide, Multi-institutional, Cross-Sectional Study of Students at DO-Granting Medical Schools,” Acad Med. 2020 Jan 21. doi: 10.1097/ACM.0000000000003175). The researchers surveyed more than 10,000 medical students at nearly 50 DO-granting medical schools using standardized questionnaire called the Jefferson Scale of Empathy. They discovered that the students in the clinical phase (years 3 and 4) had lower “empathy scores” than the students in the preclinical phase of their education (years 1 and 2). This decline was statistically significant but “negligible” in magnitude. One wonders why they even chose to publish their results, particularly when the number of respondents to the web-based survey declined with each successive year in medical school. Having looked at the a sample of some of the questions being asked, I can understand why third- and fourth-year students couldn’t be bothered to respond. They were too busy to answer a few dozen “lame” questions.

There may be a decline in empathy over the course our medical training, but I’m not sure that this study can speak to it. An older study found that although medical students scores on a self-administered scale declined between the second and third year, the observed empathetic behavior actually increased. If I had to choose, I would lean more heavily on the results of the behavioral observations.

Certainly, we all changed over the course of our medical education. Including postgraduate training, it may have lasted a decade or more. We saw hundreds of patients, observed life and death on a scale and with an intensity that most of us previously had never experienced. Our perspective changed from being a naive observer to playing the role of an active participant. Did that change include a decline in our capacity for empathy?

Something had to change. We found quickly that we didn’t have the time or emotional energy to learn as much about the person hiding behind every complaint as we once thought we should. We had to cut corners. Sometimes we cut too many. On the other hand, as we saw more patients we may have learned more efficient ways of discovering what we needed to know about them to become an effective and caring physician. If we found ourselves in a specialty in which patients have a high mortality, we were forced to learn ways of protecting ourselves from the emotional damage.

What would you call this process? Was it empathy erosion? Was it a hardening or toughening? Or was it simply maturation? Whatever term you use, it was an obligatory process if we hoped to survive. However, not all of us have done it well. Some of us have narrowed our focus to see only the complaint and the diagnosis, and we too often fail to see the human hiding in plain sight.

For those of us who completed our training with our empathy intact, was this the result of a genetic gift or the atmosphere our parents had created at home? I suspect that in most cases our capacity for empathy as physicians was nurtured and enhanced by the role models we encountered during our training. The mentors we most revered were those who had already been through the annealing process of medical school and specialty training and become even more skilled at caring than when they left college. It is an intangible that can’t be taught. Sadly, there is no way of guaranteeing that everyone who enters medical school will be exposed to or benefit from even one of these master physicians.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

You learned a lot of things in medical school. But there must have been some things that you unlearned on the way to your degree. For instance, you unlearned that you could catch a cold by playing outside on a cold damp day without your jacket. You unlearned that handling a toad would give you warts.

©KatarzynaBialasiewicz/Thinkstock

The authors of a recent study suggest that over your 4 years in medical school you also unlearned how to be empathetic (“Does Empathy Decline in the Clinical Phase of Medical Education? A Nationwide, Multi-institutional, Cross-Sectional Study of Students at DO-Granting Medical Schools,” Acad Med. 2020 Jan 21. doi: 10.1097/ACM.0000000000003175). The researchers surveyed more than 10,000 medical students at nearly 50 DO-granting medical schools using standardized questionnaire called the Jefferson Scale of Empathy. They discovered that the students in the clinical phase (years 3 and 4) had lower “empathy scores” than the students in the preclinical phase of their education (years 1 and 2). This decline was statistically significant but “negligible” in magnitude. One wonders why they even chose to publish their results, particularly when the number of respondents to the web-based survey declined with each successive year in medical school. Having looked at the a sample of some of the questions being asked, I can understand why third- and fourth-year students couldn’t be bothered to respond. They were too busy to answer a few dozen “lame” questions.

There may be a decline in empathy over the course our medical training, but I’m not sure that this study can speak to it. An older study found that although medical students scores on a self-administered scale declined between the second and third year, the observed empathetic behavior actually increased. If I had to choose, I would lean more heavily on the results of the behavioral observations.

Certainly, we all changed over the course of our medical education. Including postgraduate training, it may have lasted a decade or more. We saw hundreds of patients, observed life and death on a scale and with an intensity that most of us previously had never experienced. Our perspective changed from being a naive observer to playing the role of an active participant. Did that change include a decline in our capacity for empathy?

Something had to change. We found quickly that we didn’t have the time or emotional energy to learn as much about the person hiding behind every complaint as we once thought we should. We had to cut corners. Sometimes we cut too many. On the other hand, as we saw more patients we may have learned more efficient ways of discovering what we needed to know about them to become an effective and caring physician. If we found ourselves in a specialty in which patients have a high mortality, we were forced to learn ways of protecting ourselves from the emotional damage.

What would you call this process? Was it empathy erosion? Was it a hardening or toughening? Or was it simply maturation? Whatever term you use, it was an obligatory process if we hoped to survive. However, not all of us have done it well. Some of us have narrowed our focus to see only the complaint and the diagnosis, and we too often fail to see the human hiding in plain sight.

For those of us who completed our training with our empathy intact, was this the result of a genetic gift or the atmosphere our parents had created at home? I suspect that in most cases our capacity for empathy as physicians was nurtured and enhanced by the role models we encountered during our training. The mentors we most revered were those who had already been through the annealing process of medical school and specialty training and become even more skilled at caring than when they left college. It is an intangible that can’t be taught. Sadly, there is no way of guaranteeing that everyone who enters medical school will be exposed to or benefit from even one of these master physicians.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

You learned a lot of things in medical school. But there must have been some things that you unlearned on the way to your degree. For instance, you unlearned that you could catch a cold by playing outside on a cold damp day without your jacket. You unlearned that handling a toad would give you warts.

©KatarzynaBialasiewicz/Thinkstock

The authors of a recent study suggest that over your 4 years in medical school you also unlearned how to be empathetic (“Does Empathy Decline in the Clinical Phase of Medical Education? A Nationwide, Multi-institutional, Cross-Sectional Study of Students at DO-Granting Medical Schools,” Acad Med. 2020 Jan 21. doi: 10.1097/ACM.0000000000003175). The researchers surveyed more than 10,000 medical students at nearly 50 DO-granting medical schools using standardized questionnaire called the Jefferson Scale of Empathy. They discovered that the students in the clinical phase (years 3 and 4) had lower “empathy scores” than the students in the preclinical phase of their education (years 1 and 2). This decline was statistically significant but “negligible” in magnitude. One wonders why they even chose to publish their results, particularly when the number of respondents to the web-based survey declined with each successive year in medical school. Having looked at the a sample of some of the questions being asked, I can understand why third- and fourth-year students couldn’t be bothered to respond. They were too busy to answer a few dozen “lame” questions.

There may be a decline in empathy over the course our medical training, but I’m not sure that this study can speak to it. An older study found that although medical students scores on a self-administered scale declined between the second and third year, the observed empathetic behavior actually increased. If I had to choose, I would lean more heavily on the results of the behavioral observations.

Certainly, we all changed over the course of our medical education. Including postgraduate training, it may have lasted a decade or more. We saw hundreds of patients, observed life and death on a scale and with an intensity that most of us previously had never experienced. Our perspective changed from being a naive observer to playing the role of an active participant. Did that change include a decline in our capacity for empathy?

Something had to change. We found quickly that we didn’t have the time or emotional energy to learn as much about the person hiding behind every complaint as we once thought we should. We had to cut corners. Sometimes we cut too many. On the other hand, as we saw more patients we may have learned more efficient ways of discovering what we needed to know about them to become an effective and caring physician. If we found ourselves in a specialty in which patients have a high mortality, we were forced to learn ways of protecting ourselves from the emotional damage.

What would you call this process? Was it empathy erosion? Was it a hardening or toughening? Or was it simply maturation? Whatever term you use, it was an obligatory process if we hoped to survive. However, not all of us have done it well. Some of us have narrowed our focus to see only the complaint and the diagnosis, and we too often fail to see the human hiding in plain sight.

For those of us who completed our training with our empathy intact, was this the result of a genetic gift or the atmosphere our parents had created at home? I suspect that in most cases our capacity for empathy as physicians was nurtured and enhanced by the role models we encountered during our training. The mentors we most revered were those who had already been through the annealing process of medical school and specialty training and become even more skilled at caring than when they left college. It is an intangible that can’t be taught. Sadly, there is no way of guaranteeing that everyone who enters medical school will be exposed to or benefit from even one of these master physicians.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


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.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


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.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


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.

It’s hard to find good news these days, but I thought I had stumbled on a nice feel-good story in the Portland Press Herald. It turns out a group of students at the King Middle School in Portland, Maine, has formed a team of “compost guardians,” who by coaxing their fellow students into sorting their uneaten lunch food into five reusable or recyclable categories have reduced the cafeteria’s daily waste production from 12 40-gallon trash bags to 2. (“Each year, Maine’s K-12 schools waste about 7 million pounds of food,” by Rachel Ohm, Portland Press Herald, Feb. 2, 2020). That seems like a heroic accomplishment and good news by any standard.

monkeybusinessimages/Getty Images

However, as I read on in the newspaper article it became clear that these students’ efforts represent a tiny speck of light in the middle of a very dark tunnel. In developing their system, the students learned that 34% of the food was not being consumed, which is part of the 30%-40% of food wasted across the country. In Maine, this represents about 7 million pounds of food wasted annually. Not surprisingly, the students found that 60% of the fruit and 28% of the vegetables go uneaten.

But current federal guidelines dictate that students must take a vegetable and a fruit on their trays. While well-intentioned, this is a mandate destined to generate waste.

King Middle School and many other schools around the country offer a program that is not in the federal guidelines: a “share table” where students can place unwanted (but safe to eat) food, and from which other students may serve themselves freely. On the surface, this may seem like a good idea because it legitimizes what children have been doing for years on their own. This shared food should consist of “healthy choices” because it is cafeteria fare dictated by the United States Department of Agriculture. But you know as well as I do that a child can become obese overeating a diet that in moderate amounts would be considered healthy. I suspect that many, if not most, students taking food from the share table don’t need any extra calories.

The USDA recently announced that it will be rolling out reforms for school and summer meal programs (USDA Release # USDA 0129.20). One of the goals of these reforms is to reduce food wastage by giving schools more flexibility in creating menus and offering more à la carte options. In the wake this rollout, there has been some concern voiced that schools will begin to offer less nutritional options. Unfortunately, this concern may be true in some districts, but it is pretty clear that the current guidelines are a significant contributor to food wastage without offering much of an upside. It may be time to lessen the record-keeping burden on local food services, and allow them some leeway in creating more appealing options while taking advantage of local food sources.

With or without the new guidelines, we are asking public schools to cater to multiple cohorts of students whose parents have put them on the bus in the morning as mismanaged picky eaters.

What would have worked at home could work at school. That strategy is to offer a child a balanced diet presented in an appealing manner in a pleasant setting. Also it is not allowing any sweetened beverages or milk in excess. Children may grumble temporarily but if the strategy is applied consistently, they will take it from there. That doesn’t mean that the children have to put the food on their trays if they don’t want it. But they shouldn’t be offered a second run through the cafeteria line or a chance to pick from the share table. Sadly, the success of this strategy relies on two shaky premises: That parents will begin to apply it at home and that school lunch programs will offer only healthy choices.

The bottom line is that schools can’t be expected to cure picky eaters who were enabled at home. On the other hand, it is not unreasonable to ask schools to play a role in curbing the national scourge of food wastage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater: A Guide for the Perplexed Parent.” Email him at pdnews@mdedge.com.

It’s hard to find good news these days, but I thought I had stumbled on a nice feel-good story in the Portland Press Herald. It turns out a group of students at the King Middle School in Portland, Maine, has formed a team of “compost guardians,” who by coaxing their fellow students into sorting their uneaten lunch food into five reusable or recyclable categories have reduced the cafeteria’s daily waste production from 12 40-gallon trash bags to 2. (“Each year, Maine’s K-12 schools waste about 7 million pounds of food,” by Rachel Ohm, Portland Press Herald, Feb. 2, 2020). That seems like a heroic accomplishment and good news by any standard.

monkeybusinessimages/Getty Images

However, as I read on in the newspaper article it became clear that these students’ efforts represent a tiny speck of light in the middle of a very dark tunnel. In developing their system, the students learned that 34% of the food was not being consumed, which is part of the 30%-40% of food wasted across the country. In Maine, this represents about 7 million pounds of food wasted annually. Not surprisingly, the students found that 60% of the fruit and 28% of the vegetables go uneaten.

But current federal guidelines dictate that students must take a vegetable and a fruit on their trays. While well-intentioned, this is a mandate destined to generate waste.

King Middle School and many other schools around the country offer a program that is not in the federal guidelines: a “share table” where students can place unwanted (but safe to eat) food, and from which other students may serve themselves freely. On the surface, this may seem like a good idea because it legitimizes what children have been doing for years on their own. This shared food should consist of “healthy choices” because it is cafeteria fare dictated by the United States Department of Agriculture. But you know as well as I do that a child can become obese overeating a diet that in moderate amounts would be considered healthy. I suspect that many, if not most, students taking food from the share table don’t need any extra calories.

The USDA recently announced that it will be rolling out reforms for school and summer meal programs (USDA Release # USDA 0129.20). One of the goals of these reforms is to reduce food wastage by giving schools more flexibility in creating menus and offering more à la carte options. In the wake this rollout, there has been some concern voiced that schools will begin to offer less nutritional options. Unfortunately, this concern may be true in some districts, but it is pretty clear that the current guidelines are a significant contributor to food wastage without offering much of an upside. It may be time to lessen the record-keeping burden on local food services, and allow them some leeway in creating more appealing options while taking advantage of local food sources.

With or without the new guidelines, we are asking public schools to cater to multiple cohorts of students whose parents have put them on the bus in the morning as mismanaged picky eaters.

What would have worked at home could work at school. That strategy is to offer a child a balanced diet presented in an appealing manner in a pleasant setting. Also it is not allowing any sweetened beverages or milk in excess. Children may grumble temporarily but if the strategy is applied consistently, they will take it from there. That doesn’t mean that the children have to put the food on their trays if they don’t want it. But they shouldn’t be offered a second run through the cafeteria line or a chance to pick from the share table. Sadly, the success of this strategy relies on two shaky premises: That parents will begin to apply it at home and that school lunch programs will offer only healthy choices.

The bottom line is that schools can’t be expected to cure picky eaters who were enabled at home. On the other hand, it is not unreasonable to ask schools to play a role in curbing the national scourge of food wastage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater: A Guide for the Perplexed Parent.” Email him at pdnews@mdedge.com.

It’s hard to find good news these days, but I thought I had stumbled on a nice feel-good story in the Portland Press Herald. It turns out a group of students at the King Middle School in Portland, Maine, has formed a team of “compost guardians,” who by coaxing their fellow students into sorting their uneaten lunch food into five reusable or recyclable categories have reduced the cafeteria’s daily waste production from 12 40-gallon trash bags to 2. (“Each year, Maine’s K-12 schools waste about 7 million pounds of food,” by Rachel Ohm, Portland Press Herald, Feb. 2, 2020). That seems like a heroic accomplishment and good news by any standard.

monkeybusinessimages/Getty Images

However, as I read on in the newspaper article it became clear that these students’ efforts represent a tiny speck of light in the middle of a very dark tunnel. In developing their system, the students learned that 34% of the food was not being consumed, which is part of the 30%-40% of food wasted across the country. In Maine, this represents about 7 million pounds of food wasted annually. Not surprisingly, the students found that 60% of the fruit and 28% of the vegetables go uneaten.

But current federal guidelines dictate that students must take a vegetable and a fruit on their trays. While well-intentioned, this is a mandate destined to generate waste.

King Middle School and many other schools around the country offer a program that is not in the federal guidelines: a “share table” where students can place unwanted (but safe to eat) food, and from which other students may serve themselves freely. On the surface, this may seem like a good idea because it legitimizes what children have been doing for years on their own. This shared food should consist of “healthy choices” because it is cafeteria fare dictated by the United States Department of Agriculture. But you know as well as I do that a child can become obese overeating a diet that in moderate amounts would be considered healthy. I suspect that many, if not most, students taking food from the share table don’t need any extra calories.

The USDA recently announced that it will be rolling out reforms for school and summer meal programs (USDA Release # USDA 0129.20). One of the goals of these reforms is to reduce food wastage by giving schools more flexibility in creating menus and offering more à la carte options. In the wake this rollout, there has been some concern voiced that schools will begin to offer less nutritional options. Unfortunately, this concern may be true in some districts, but it is pretty clear that the current guidelines are a significant contributor to food wastage without offering much of an upside. It may be time to lessen the record-keeping burden on local food services, and allow them some leeway in creating more appealing options while taking advantage of local food sources.

With or without the new guidelines, we are asking public schools to cater to multiple cohorts of students whose parents have put them on the bus in the morning as mismanaged picky eaters.

What would have worked at home could work at school. That strategy is to offer a child a balanced diet presented in an appealing manner in a pleasant setting. Also it is not allowing any sweetened beverages or milk in excess. Children may grumble temporarily but if the strategy is applied consistently, they will take it from there. That doesn’t mean that the children have to put the food on their trays if they don’t want it. But they shouldn’t be offered a second run through the cafeteria line or a chance to pick from the share table. Sadly, the success of this strategy relies on two shaky premises: That parents will begin to apply it at home and that school lunch programs will offer only healthy choices.

The bottom line is that schools can’t be expected to cure picky eaters who were enabled at home. On the other hand, it is not unreasonable to ask schools to play a role in curbing the national scourge of food wastage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater: A Guide for the Perplexed Parent.” Email him at pdnews@mdedge.com.

Over the past years, I have had the opportunity to attend countless lectures on burnout provided by colleagues spanning across many fields in mental health and health care in general. The talks generally follow a common narration: 1. Your work is important and meaningful to many. 2. Your work requires significant training, dedication, and passion. 3. While you get personal gratification from your work, it does come with a cost. 4. This cost can be great and can affect you physically and mentally. 5. This cost is called burnout.

Burnout is described as irritability (poor mood), low energy, poor concentration, difficulty appreciating enjoyable things (anhedonia), and poor sleep, among other symptoms, as a result of work stress. At this point in the lectures, I usually ask whomever is sitting next to me: “I came in late, is this a lecture on depression?” to which the answer is typically “No! Of course not, this is about ‘burnout’ not mental illness.” And here lies a concern about burnout: Is burnout a concept describing depression that we have repackaged to protect professionals from the stigmatization of mental illness? Does our tendency not to characterize patients’ struggles as burnout stigmatize them – and imply that their employment is not challenging to cause burnout?

According to the literature, a range of factors affects burnout in professionals: lack of control, unclear job expectations, dysfunctional workplace dynamics, extremes of activity, lack of social support, work-life imbalance. Contrary to depression, burnout is not caused by neurobiological problems. Patients with burnout don’t have chemical imbalances, hyperactive default mode networks, or overactive amygdalas. Burnout is caused by social factors and affects dedicated, caring, and exceptional individuals who have been pushed outside their window of tolerance.

Literature suggests a variety of remedies to treat burnout: Reevaluate your employment, discuss occupational concerns with your supervisor, discuss with colleagues, receive help from your social support system, and seek human resources services. In addition, experts recommend engaging in relaxing activities, improving your sleep hygiene, exercising regularly, and participating in mindfulness to reduce symptoms. Contrary to depression, burnout does not require individuals to fix their maladaptive thoughts or discover inadequate unconscious beliefs that may be affecting their work. Contrary to depression, burnout does not require the rebalancing of neurochemistry using psychotropic medication.

The concept of burnout engenders concerns. I fear that it divides physicians and patients into two different classes and thus further stigmatizes those with mental illness. It implies that we physicians are somehow immune from mental illness and its consequences. We do not suffer from brain abnormalities, we do not require mind-altering medications, we are not “mentally ill.” Contrarily, at times it might be implied that patients’ jobs are not important enough to cause burnout; if they feel sad, anhedonic, have poor energy and poor sleep, it is because they have mental illness. Their brains are inadequate and flawed. But for physicians, our brains are intact, just pushed beyond human capabilities.

I should point out that I do not think that burnout experts believe or desire to promote such concepts. I am not aware of burnout experts championing physician exceptionalism or promoting the stigmatization of patients. I believe that this problem is an unintended consequence, a side effect, of the idea of burnout itself.

Another concern I have is that the concept of burnout may actually hinder physicians from seeking necessary and appropriate professional services to address symptoms. Interestingly, most lectures I have attended on burnout have not discussed the concerning number of physicians who end their lives by suicide. Burnout can give physicians the impression that their problems are social and occupational, thus not requiring a medical solution or intervention. There was a time when I argued against the removal of the grief exclusion in the DSM; I worried that we were pathologizing natural emotional reactions to trauma. However, I have come to realize that, if someone is debilitated by depression, seeking professional help should not be predicated on the trigger. As such, I would recommend the vast number of physicians who state burnout in surveys to seriously consider the possibility that they may, in fact, be suffering from mental illness. We encourage our patients to seek help and speak out against stigmatization; isn’t it time that we as professionals should not be afraid to do the same?

I have concerns about the concept of burnout, but I certainly do not think that we should get rid of the idea. On the contrary, I applaud this attempt at de-pathologizing, and de-medicalizing human suffering. As many have argued with more or less success and controversy of the years, many emotional problems are not best suited to be treated by psychotropic medication or even psychiatry. I think that psychiatry should embrace paradigms that include social and occupational constructs of emotional pain, not rooted in diseases and/or chemical imbalances. Such paradigms should, furthermore, not be limited to certain professions or life circumstances. We are all affected by human suffering. Access and willingness to appropriate care or support should not be granted only to those with a mental illness diagnosis.

Burnout is a promising idea that challenges our conceptualization of mental disorders. Burnout brings a humanity to emotional pain frequently lost in the medicalized diagnoses of the DSM. Psychiatry should seriously consider opening its door to nonmedicalized understanding of psychological suffering. By opening those doors, we begin to create a less medicalized construct for human suffering. We begin to create one based on shared human experience.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).

Over the past years, I have had the opportunity to attend countless lectures on burnout provided by colleagues spanning across many fields in mental health and health care in general. The talks generally follow a common narration: 1. Your work is important and meaningful to many. 2. Your work requires significant training, dedication, and passion. 3. While you get personal gratification from your work, it does come with a cost. 4. This cost can be great and can affect you physically and mentally. 5. This cost is called burnout.

Burnout is described as irritability (poor mood), low energy, poor concentration, difficulty appreciating enjoyable things (anhedonia), and poor sleep, among other symptoms, as a result of work stress. At this point in the lectures, I usually ask whomever is sitting next to me: “I came in late, is this a lecture on depression?” to which the answer is typically “No! Of course not, this is about ‘burnout’ not mental illness.” And here lies a concern about burnout: Is burnout a concept describing depression that we have repackaged to protect professionals from the stigmatization of mental illness? Does our tendency not to characterize patients’ struggles as burnout stigmatize them – and imply that their employment is not challenging to cause burnout?

According to the literature, a range of factors affects burnout in professionals: lack of control, unclear job expectations, dysfunctional workplace dynamics, extremes of activity, lack of social support, work-life imbalance. Contrary to depression, burnout is not caused by neurobiological problems. Patients with burnout don’t have chemical imbalances, hyperactive default mode networks, or overactive amygdalas. Burnout is caused by social factors and affects dedicated, caring, and exceptional individuals who have been pushed outside their window of tolerance.

Literature suggests a variety of remedies to treat burnout: Reevaluate your employment, discuss occupational concerns with your supervisor, discuss with colleagues, receive help from your social support system, and seek human resources services. In addition, experts recommend engaging in relaxing activities, improving your sleep hygiene, exercising regularly, and participating in mindfulness to reduce symptoms. Contrary to depression, burnout does not require individuals to fix their maladaptive thoughts or discover inadequate unconscious beliefs that may be affecting their work. Contrary to depression, burnout does not require the rebalancing of neurochemistry using psychotropic medication.

The concept of burnout engenders concerns. I fear that it divides physicians and patients into two different classes and thus further stigmatizes those with mental illness. It implies that we physicians are somehow immune from mental illness and its consequences. We do not suffer from brain abnormalities, we do not require mind-altering medications, we are not “mentally ill.” Contrarily, at times it might be implied that patients’ jobs are not important enough to cause burnout; if they feel sad, anhedonic, have poor energy and poor sleep, it is because they have mental illness. Their brains are inadequate and flawed. But for physicians, our brains are intact, just pushed beyond human capabilities.

I should point out that I do not think that burnout experts believe or desire to promote such concepts. I am not aware of burnout experts championing physician exceptionalism or promoting the stigmatization of patients. I believe that this problem is an unintended consequence, a side effect, of the idea of burnout itself.

Another concern I have is that the concept of burnout may actually hinder physicians from seeking necessary and appropriate professional services to address symptoms. Interestingly, most lectures I have attended on burnout have not discussed the concerning number of physicians who end their lives by suicide. Burnout can give physicians the impression that their problems are social and occupational, thus not requiring a medical solution or intervention. There was a time when I argued against the removal of the grief exclusion in the DSM; I worried that we were pathologizing natural emotional reactions to trauma. However, I have come to realize that, if someone is debilitated by depression, seeking professional help should not be predicated on the trigger. As such, I would recommend the vast number of physicians who state burnout in surveys to seriously consider the possibility that they may, in fact, be suffering from mental illness. We encourage our patients to seek help and speak out against stigmatization; isn’t it time that we as professionals should not be afraid to do the same?

I have concerns about the concept of burnout, but I certainly do not think that we should get rid of the idea. On the contrary, I applaud this attempt at de-pathologizing, and de-medicalizing human suffering. As many have argued with more or less success and controversy of the years, many emotional problems are not best suited to be treated by psychotropic medication or even psychiatry. I think that psychiatry should embrace paradigms that include social and occupational constructs of emotional pain, not rooted in diseases and/or chemical imbalances. Such paradigms should, furthermore, not be limited to certain professions or life circumstances. We are all affected by human suffering. Access and willingness to appropriate care or support should not be granted only to those with a mental illness diagnosis.

Burnout is a promising idea that challenges our conceptualization of mental disorders. Burnout brings a humanity to emotional pain frequently lost in the medicalized diagnoses of the DSM. Psychiatry should seriously consider opening its door to nonmedicalized understanding of psychological suffering. By opening those doors, we begin to create a less medicalized construct for human suffering. We begin to create one based on shared human experience.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).

Over the past years, I have had the opportunity to attend countless lectures on burnout provided by colleagues spanning across many fields in mental health and health care in general. The talks generally follow a common narration: 1. Your work is important and meaningful to many. 2. Your work requires significant training, dedication, and passion. 3. While you get personal gratification from your work, it does come with a cost. 4. This cost can be great and can affect you physically and mentally. 5. This cost is called burnout.

Burnout is described as irritability (poor mood), low energy, poor concentration, difficulty appreciating enjoyable things (anhedonia), and poor sleep, among other symptoms, as a result of work stress. At this point in the lectures, I usually ask whomever is sitting next to me: “I came in late, is this a lecture on depression?” to which the answer is typically “No! Of course not, this is about ‘burnout’ not mental illness.” And here lies a concern about burnout: Is burnout a concept describing depression that we have repackaged to protect professionals from the stigmatization of mental illness? Does our tendency not to characterize patients’ struggles as burnout stigmatize them – and imply that their employment is not challenging to cause burnout?

According to the literature, a range of factors affects burnout in professionals: lack of control, unclear job expectations, dysfunctional workplace dynamics, extremes of activity, lack of social support, work-life imbalance. Contrary to depression, burnout is not caused by neurobiological problems. Patients with burnout don’t have chemical imbalances, hyperactive default mode networks, or overactive amygdalas. Burnout is caused by social factors and affects dedicated, caring, and exceptional individuals who have been pushed outside their window of tolerance.

Literature suggests a variety of remedies to treat burnout: Reevaluate your employment, discuss occupational concerns with your supervisor, discuss with colleagues, receive help from your social support system, and seek human resources services. In addition, experts recommend engaging in relaxing activities, improving your sleep hygiene, exercising regularly, and participating in mindfulness to reduce symptoms. Contrary to depression, burnout does not require individuals to fix their maladaptive thoughts or discover inadequate unconscious beliefs that may be affecting their work. Contrary to depression, burnout does not require the rebalancing of neurochemistry using psychotropic medication.

The concept of burnout engenders concerns. I fear that it divides physicians and patients into two different classes and thus further stigmatizes those with mental illness. It implies that we physicians are somehow immune from mental illness and its consequences. We do not suffer from brain abnormalities, we do not require mind-altering medications, we are not “mentally ill.” Contrarily, at times it might be implied that patients’ jobs are not important enough to cause burnout; if they feel sad, anhedonic, have poor energy and poor sleep, it is because they have mental illness. Their brains are inadequate and flawed. But for physicians, our brains are intact, just pushed beyond human capabilities.

I should point out that I do not think that burnout experts believe or desire to promote such concepts. I am not aware of burnout experts championing physician exceptionalism or promoting the stigmatization of patients. I believe that this problem is an unintended consequence, a side effect, of the idea of burnout itself.

Another concern I have is that the concept of burnout may actually hinder physicians from seeking necessary and appropriate professional services to address symptoms. Interestingly, most lectures I have attended on burnout have not discussed the concerning number of physicians who end their lives by suicide. Burnout can give physicians the impression that their problems are social and occupational, thus not requiring a medical solution or intervention. There was a time when I argued against the removal of the grief exclusion in the DSM; I worried that we were pathologizing natural emotional reactions to trauma. However, I have come to realize that, if someone is debilitated by depression, seeking professional help should not be predicated on the trigger. As such, I would recommend the vast number of physicians who state burnout in surveys to seriously consider the possibility that they may, in fact, be suffering from mental illness. We encourage our patients to seek help and speak out against stigmatization; isn’t it time that we as professionals should not be afraid to do the same?

I have concerns about the concept of burnout, but I certainly do not think that we should get rid of the idea. On the contrary, I applaud this attempt at de-pathologizing, and de-medicalizing human suffering. As many have argued with more or less success and controversy of the years, many emotional problems are not best suited to be treated by psychotropic medication or even psychiatry. I think that psychiatry should embrace paradigms that include social and occupational constructs of emotional pain, not rooted in diseases and/or chemical imbalances. Such paradigms should, furthermore, not be limited to certain professions or life circumstances. We are all affected by human suffering. Access and willingness to appropriate care or support should not be granted only to those with a mental illness diagnosis.

Burnout is a promising idea that challenges our conceptualization of mental disorders. Burnout brings a humanity to emotional pain frequently lost in the medicalized diagnoses of the DSM. Psychiatry should seriously consider opening its door to nonmedicalized understanding of psychological suffering. By opening those doors, we begin to create a less medicalized construct for human suffering. We begin to create one based on shared human experience.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).

We are in the healing profession. We practice a trade. We are doctors, therapists, counselors. We work with children, adults, and couples. We document the physical form of our patient after examination, setting the stage for interventions that heal and alleviate suffering. With those who we do not touch physically, we hold out our psychological arms to embrace them in a therapeutic relationship.

We are privileged to appreciate their deeper selves through voice, unsaid words, and body language. A trust evolves (or might not); deeper exploration where our intuition and technical skill discover what troubles the soul. Healing begins as a delicate dance: As trust is earned, our patients risk vulnerability by revealing their weakest selves.

As healers, we often find ourselves adrift with our own insecurities, our own histories that make us human; our styles may differ but training and the tenets and guidelines set by our professional societies keep us in safe waters. These guidelines are informed by the science of health care research and vetted through centuries of observation and experience of process. “Do no harm” is perhaps one of the major rules of engaging with patients. The scaffolding that our code of ethics provides healing professions trumps external pressures to deviate. If you violate these codes, the consequences are borne by the patient and the potential loss of your license.

Some of you may have read about Kevin Euceda, an adolescent who reportedly was waiting for his immigration interview and ordered to undergo mandatory therapy as part of the immigration protocol. Kevin revealed to his therapist the history of violence he experienced as a child growing up in Honduras. His subsequent initiation into a gang was the only option he had to escape a violent death. Those of us who work with youth from gang cultures know fully that allegiance to a gang is a means to find an identity and brotherhood with the payment by a lifestyle of violence. A therapist faced with this information does not judge but helps the person deal with PTSD, nightmares, and guilt that become part of an identity just as the memories of mines blowing up in the face of combat affect veterans.

But the therapist, who reportedly holds a master’s in rehabilitation counseling and was “a year away from passing her licensing exam,” according to an article published in the Washington Post, followed policy of the Office of Refugee Resettlement. The therapist betrayed Kevin by reporting the information he shared with her confidentially to Immigration and Customs Enforcement. The reason the therapist gave for the breach was that she was compelled do so because Kevin reported participating in gang activity in Honduras. Subsequently, Kevin was sent to a high-security detention center – and is now facing deportation.
 

Betraying a patient, profession

Therapy begins as a contract between patient and therapist. The contract stipulates that all that transpires in the process of therapy (usually a 50-minute block of time, usually weekly) is information held by the therapist and patient – and is not to be shared with anyone, including parents, guardians, legal entities, and health care agencies. This allows the gradual sharing of events, emotions, behaviors, and reactions akin to peeling an onion. Memories, reactions, and feelings assist the therapist as they start their quest of discovery of the conflict and how to resolve it. Trust is the central tenet of this journey. The patient thinks: “You will hear me; you will see me you will understand me and help me understand myself.” The doctor responds: “Even I don’t yet know fully what ails you; we will discover that together. … I will not fail your trust.”

So how does this interface with external pressures? The constitution of a free country provides some inviolable protections that prevent derailment of the codes of ethics based on science. The fine line between what are considered sacrosanct ethics of a field – be it health care, climatology, or architecture – and what could be sacrificed in the name of prevailing forces (political or otherwise) has to be under constant scrutiny by the members of the guild. In health care, when patients cannot trust the science, its implementation, or is let down by the clinician, they are unlikely to benefit from treatment. A foundation of distrust paves the way for future therapeutic relationships that are stained with distrust and noncompliance.

The ethics guidelines of the American Academy of Psychiatry and the Law specify that psychiatrists in forensic roles “should be clear about limitations on confidentiality in the treatment relationship and ensure that these limitations are communicated to the patient.” Again, the therapist in this case is not a psychiatrist, but I would argue that the same rules would apply.

It is reassuring to know that several key groups, including the American Psychiatric Association, American Academy of Child and Adolescent Psychiatry, and the American Psychological Association, have all condemned the therapist’s actions. Psychiatrists and other mental health professionals must do no harm. We must not stand idly by and allow the kind of professional breach that happened to Kevin continue. Patients who confide in mental health professionals with the promise of confidentiality must be able to do so without fear. Only with confidentiality can the therapeutic relationship thrive.

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy, at Virginia Commonwealth University, Richmond.

We are in the healing profession. We practice a trade. We are doctors, therapists, counselors. We work with children, adults, and couples. We document the physical form of our patient after examination, setting the stage for interventions that heal and alleviate suffering. With those who we do not touch physically, we hold out our psychological arms to embrace them in a therapeutic relationship.

We are privileged to appreciate their deeper selves through voice, unsaid words, and body language. A trust evolves (or might not); deeper exploration where our intuition and technical skill discover what troubles the soul. Healing begins as a delicate dance: As trust is earned, our patients risk vulnerability by revealing their weakest selves.

As healers, we often find ourselves adrift with our own insecurities, our own histories that make us human; our styles may differ but training and the tenets and guidelines set by our professional societies keep us in safe waters. These guidelines are informed by the science of health care research and vetted through centuries of observation and experience of process. “Do no harm” is perhaps one of the major rules of engaging with patients. The scaffolding that our code of ethics provides healing professions trumps external pressures to deviate. If you violate these codes, the consequences are borne by the patient and the potential loss of your license.

Some of you may have read about Kevin Euceda, an adolescent who reportedly was waiting for his immigration interview and ordered to undergo mandatory therapy as part of the immigration protocol. Kevin revealed to his therapist the history of violence he experienced as a child growing up in Honduras. His subsequent initiation into a gang was the only option he had to escape a violent death. Those of us who work with youth from gang cultures know fully that allegiance to a gang is a means to find an identity and brotherhood with the payment by a lifestyle of violence. A therapist faced with this information does not judge but helps the person deal with PTSD, nightmares, and guilt that become part of an identity just as the memories of mines blowing up in the face of combat affect veterans.

But the therapist, who reportedly holds a master’s in rehabilitation counseling and was “a year away from passing her licensing exam,” according to an article published in the Washington Post, followed policy of the Office of Refugee Resettlement. The therapist betrayed Kevin by reporting the information he shared with her confidentially to Immigration and Customs Enforcement. The reason the therapist gave for the breach was that she was compelled do so because Kevin reported participating in gang activity in Honduras. Subsequently, Kevin was sent to a high-security detention center – and is now facing deportation.
 

Betraying a patient, profession

Therapy begins as a contract between patient and therapist. The contract stipulates that all that transpires in the process of therapy (usually a 50-minute block of time, usually weekly) is information held by the therapist and patient – and is not to be shared with anyone, including parents, guardians, legal entities, and health care agencies. This allows the gradual sharing of events, emotions, behaviors, and reactions akin to peeling an onion. Memories, reactions, and feelings assist the therapist as they start their quest of discovery of the conflict and how to resolve it. Trust is the central tenet of this journey. The patient thinks: “You will hear me; you will see me you will understand me and help me understand myself.” The doctor responds: “Even I don’t yet know fully what ails you; we will discover that together. … I will not fail your trust.”

So how does this interface with external pressures? The constitution of a free country provides some inviolable protections that prevent derailment of the codes of ethics based on science. The fine line between what are considered sacrosanct ethics of a field – be it health care, climatology, or architecture – and what could be sacrificed in the name of prevailing forces (political or otherwise) has to be under constant scrutiny by the members of the guild. In health care, when patients cannot trust the science, its implementation, or is let down by the clinician, they are unlikely to benefit from treatment. A foundation of distrust paves the way for future therapeutic relationships that are stained with distrust and noncompliance.

The ethics guidelines of the American Academy of Psychiatry and the Law specify that psychiatrists in forensic roles “should be clear about limitations on confidentiality in the treatment relationship and ensure that these limitations are communicated to the patient.” Again, the therapist in this case is not a psychiatrist, but I would argue that the same rules would apply.

It is reassuring to know that several key groups, including the American Psychiatric Association, American Academy of Child and Adolescent Psychiatry, and the American Psychological Association, have all condemned the therapist’s actions. Psychiatrists and other mental health professionals must do no harm. We must not stand idly by and allow the kind of professional breach that happened to Kevin continue. Patients who confide in mental health professionals with the promise of confidentiality must be able to do so without fear. Only with confidentiality can the therapeutic relationship thrive.

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy, at Virginia Commonwealth University, Richmond.

We are in the healing profession. We practice a trade. We are doctors, therapists, counselors. We work with children, adults, and couples. We document the physical form of our patient after examination, setting the stage for interventions that heal and alleviate suffering. With those who we do not touch physically, we hold out our psychological arms to embrace them in a therapeutic relationship.

We are privileged to appreciate their deeper selves through voice, unsaid words, and body language. A trust evolves (or might not); deeper exploration where our intuition and technical skill discover what troubles the soul. Healing begins as a delicate dance: As trust is earned, our patients risk vulnerability by revealing their weakest selves.

As healers, we often find ourselves adrift with our own insecurities, our own histories that make us human; our styles may differ but training and the tenets and guidelines set by our professional societies keep us in safe waters. These guidelines are informed by the science of health care research and vetted through centuries of observation and experience of process. “Do no harm” is perhaps one of the major rules of engaging with patients. The scaffolding that our code of ethics provides healing professions trumps external pressures to deviate. If you violate these codes, the consequences are borne by the patient and the potential loss of your license.

Some of you may have read about Kevin Euceda, an adolescent who reportedly was waiting for his immigration interview and ordered to undergo mandatory therapy as part of the immigration protocol. Kevin revealed to his therapist the history of violence he experienced as a child growing up in Honduras. His subsequent initiation into a gang was the only option he had to escape a violent death. Those of us who work with youth from gang cultures know fully that allegiance to a gang is a means to find an identity and brotherhood with the payment by a lifestyle of violence. A therapist faced with this information does not judge but helps the person deal with PTSD, nightmares, and guilt that become part of an identity just as the memories of mines blowing up in the face of combat affect veterans.

But the therapist, who reportedly holds a master’s in rehabilitation counseling and was “a year away from passing her licensing exam,” according to an article published in the Washington Post, followed policy of the Office of Refugee Resettlement. The therapist betrayed Kevin by reporting the information he shared with her confidentially to Immigration and Customs Enforcement. The reason the therapist gave for the breach was that she was compelled do so because Kevin reported participating in gang activity in Honduras. Subsequently, Kevin was sent to a high-security detention center – and is now facing deportation.
 

Betraying a patient, profession

Therapy begins as a contract between patient and therapist. The contract stipulates that all that transpires in the process of therapy (usually a 50-minute block of time, usually weekly) is information held by the therapist and patient – and is not to be shared with anyone, including parents, guardians, legal entities, and health care agencies. This allows the gradual sharing of events, emotions, behaviors, and reactions akin to peeling an onion. Memories, reactions, and feelings assist the therapist as they start their quest of discovery of the conflict and how to resolve it. Trust is the central tenet of this journey. The patient thinks: “You will hear me; you will see me you will understand me and help me understand myself.” The doctor responds: “Even I don’t yet know fully what ails you; we will discover that together. … I will not fail your trust.”

So how does this interface with external pressures? The constitution of a free country provides some inviolable protections that prevent derailment of the codes of ethics based on science. The fine line between what are considered sacrosanct ethics of a field – be it health care, climatology, or architecture – and what could be sacrificed in the name of prevailing forces (political or otherwise) has to be under constant scrutiny by the members of the guild. In health care, when patients cannot trust the science, its implementation, or is let down by the clinician, they are unlikely to benefit from treatment. A foundation of distrust paves the way for future therapeutic relationships that are stained with distrust and noncompliance.

The ethics guidelines of the American Academy of Psychiatry and the Law specify that psychiatrists in forensic roles “should be clear about limitations on confidentiality in the treatment relationship and ensure that these limitations are communicated to the patient.” Again, the therapist in this case is not a psychiatrist, but I would argue that the same rules would apply.

It is reassuring to know that several key groups, including the American Psychiatric Association, American Academy of Child and Adolescent Psychiatry, and the American Psychological Association, have all condemned the therapist’s actions. Psychiatrists and other mental health professionals must do no harm. We must not stand idly by and allow the kind of professional breach that happened to Kevin continue. Patients who confide in mental health professionals with the promise of confidentiality must be able to do so without fear. Only with confidentiality can the therapeutic relationship thrive.

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy, at Virginia Commonwealth University, Richmond.

With the novel coronavirus (COVID-19) monopolizing the news cycle, fear and misinformation are at an all-time high. Public health officials and physicians are accelerating education outreach to the public to address misinformation, and identify and care for patients who may have been exposed to the virus.

In times of public health crises, pregnant women have unique and pressing concerns about their personal health and the health of their unborn children. While not often mentioned in major news coverage, obstetricians play a critical role during health crises because of their uniquely personal role with patients during all stages of pregnancy, providing this vulnerable population with the most up-to-date information and following the latest guidelines for recommended care.

Unfortunately, COVID-19 is breaking unfamiliar new ground. We know that pregnant women are at higher risk for viral infection – annually, influenza is a grim reminder that pregnant women are more immunocompromised than the general public – but we do not yet have data to confirm or refute that pregnant women have a higher susceptibility to COVID-19 than the rest of the adult population. We also do not know enough about COVID-19 transmission, including whether the virus can cross the transplacental barrier to affect a fetus, or whether it can be transmitted through breast milk. 

As private practice community obstetricians work to protect their patients during this public health crisis, Ob hospitalists can play an important role in supporting them in the provision of patient care. 

First, Ob hospitalists are highly-trained specialists who can help ensure that pregnant patients who seek care at the hospital – either with viral symptoms or with separate pregnancy-related concerns – are protected during triage until the treating community obstetrician can take the reins.

When a pregnant woman presents at a hospital, in most cases she will bypass the ED and instead be sent directly to the labor and delivery (L&D) unit. During a viral outbreak, there are two major concerns with this approach. For one thing, it means an immunocompromised woman is being sent through the hospital to get to L&D, and along the path, is exposed to every airborne pathogen in the facility (and, if she is already infected, exposes others along the way). In addition, in hospitals without an Ob hospitalist on site, the patient generally is not immediately triaged by a physician, physician’s assistant, or nurse practitioner upon arrival because those clinicians are not consistently on site in L&D.

In times of viral pandemics, new approaches are warranted. For hospitals with contracted L&D management with hospitalists, hospitalists work closely with department heads to implement protocols loosely based on the Emergency Severity Index (ESI) model established by the Agency for Healthcare Research and Quality. Just as the ESI algorithm guides clinical stratification of patients, in times of reported viral outbreaks, L&D should consider triage of all pregnant women at higher levels of acuity, regardless of presentation status. In particular, if they show clinical symptoms, they should be masked, accompanied to the L&D unit by protected personnel, separated from other patients in areas of forced proximity such as hallways and elevators, and triaged in a secure single-patient room with a closed door (ideally at negative pressure relative to the surrounding areas). 

If the patient has traveled to an area of outbreak, reports exposure to travelers who have visited high-risk areas, has had contact with individuals who tested positive for COVID-19, or exhibits any clinical symptoms of COVID-19 (fever, dry cough, fatigue, etc.), her care management should adhere to standing hospital emergency protocols. Following consultation with the assigned community obstetrician, the Ob hospitalist and hospital staff should contact their local/state health departments immediately for all cases of patients who show symptoms to determine if the patient meets requirements for a person under investigation (PUI) for COVID-19. The state/local health department will work with clinicians to collect, store, and ship clinical specimens appropriately. Very ill patients may need to be treated in an intensive care setting where respiratory status can be closely monitored.

At Ob Hospitalist Group, our body of evidence from our large national footprint has informed the development of standard sets of protocols for delivery complications such as preeclampsia and postpartum hemorrhage, as well as a cesarean section reduction toolkit to combat medically unnecessary cesarean sections. OB hospitalists therefore can assist with refining COVID-19 protocols specifically for the L&D setting, using evidence-based data to tailor protocols to address public health emergencies as they evolve.

The second way that Ob hospitalists can support their colleagues is by covering L&D 24/7 so that community obstetricians can focus on other pressing medical needs. From our experience with other outbreaks such as severe acute respiratory syndrome (SARS) and influenza, we anticipate that obstetricians in private practice likely will have their hands full juggling a regular patient load, fielding calls from concerned patients, and caring for infected or ill patients who are being treated in an outpatient setting. Adding to that plate the need to rush to the hospital to clinically assess a patient for COVID-19 or for a delivery only compounds stress and exhaustion. At Ob Hospitalist Group, our hospitalist programs provide coverage and support to community obstetricians until they can arrive at the hospital or when the woman has no assigned obstetrician, reducing the pressure on community obstetricians to rush through their schedules.

Diagnostic and pharmaceutical companies are collaborating with public health officials to expedite diagnostic testing staff, hospital treatment capacity, vaccines, and even early therapies that may help to minimize severity. But right now, as clinicians work to protect their vulnerable patients, a close collaboration between community obstetricians and Ob hospitalists will help to keep patients and health care personnel safe and healthy – a goal that should apply not only to public health crises, but to the provision of maternal care every day.
 

Dr. Simon is chief medical officer at Ob Hospitalist Group (OBHG), is a board-certified ob.gyn., and former head of the department of obstetrics and gynecology for a U.S. hospital. He has no relevant conflicts of interest or financial disclosures. Email him at obnews@mdedge.com.

With the novel coronavirus (COVID-19) monopolizing the news cycle, fear and misinformation are at an all-time high. Public health officials and physicians are accelerating education outreach to the public to address misinformation, and identify and care for patients who may have been exposed to the virus.

In times of public health crises, pregnant women have unique and pressing concerns about their personal health and the health of their unborn children. While not often mentioned in major news coverage, obstetricians play a critical role during health crises because of their uniquely personal role with patients during all stages of pregnancy, providing this vulnerable population with the most up-to-date information and following the latest guidelines for recommended care.

Unfortunately, COVID-19 is breaking unfamiliar new ground. We know that pregnant women are at higher risk for viral infection – annually, influenza is a grim reminder that pregnant women are more immunocompromised than the general public – but we do not yet have data to confirm or refute that pregnant women have a higher susceptibility to COVID-19 than the rest of the adult population. We also do not know enough about COVID-19 transmission, including whether the virus can cross the transplacental barrier to affect a fetus, or whether it can be transmitted through breast milk. 

As private practice community obstetricians work to protect their patients during this public health crisis, Ob hospitalists can play an important role in supporting them in the provision of patient care. 

First, Ob hospitalists are highly-trained specialists who can help ensure that pregnant patients who seek care at the hospital – either with viral symptoms or with separate pregnancy-related concerns – are protected during triage until the treating community obstetrician can take the reins.

When a pregnant woman presents at a hospital, in most cases she will bypass the ED and instead be sent directly to the labor and delivery (L&D) unit. During a viral outbreak, there are two major concerns with this approach. For one thing, it means an immunocompromised woman is being sent through the hospital to get to L&D, and along the path, is exposed to every airborne pathogen in the facility (and, if she is already infected, exposes others along the way). In addition, in hospitals without an Ob hospitalist on site, the patient generally is not immediately triaged by a physician, physician’s assistant, or nurse practitioner upon arrival because those clinicians are not consistently on site in L&D.

In times of viral pandemics, new approaches are warranted. For hospitals with contracted L&D management with hospitalists, hospitalists work closely with department heads to implement protocols loosely based on the Emergency Severity Index (ESI) model established by the Agency for Healthcare Research and Quality. Just as the ESI algorithm guides clinical stratification of patients, in times of reported viral outbreaks, L&D should consider triage of all pregnant women at higher levels of acuity, regardless of presentation status. In particular, if they show clinical symptoms, they should be masked, accompanied to the L&D unit by protected personnel, separated from other patients in areas of forced proximity such as hallways and elevators, and triaged in a secure single-patient room with a closed door (ideally at negative pressure relative to the surrounding areas). 

If the patient has traveled to an area of outbreak, reports exposure to travelers who have visited high-risk areas, has had contact with individuals who tested positive for COVID-19, or exhibits any clinical symptoms of COVID-19 (fever, dry cough, fatigue, etc.), her care management should adhere to standing hospital emergency protocols. Following consultation with the assigned community obstetrician, the Ob hospitalist and hospital staff should contact their local/state health departments immediately for all cases of patients who show symptoms to determine if the patient meets requirements for a person under investigation (PUI) for COVID-19. The state/local health department will work with clinicians to collect, store, and ship clinical specimens appropriately. Very ill patients may need to be treated in an intensive care setting where respiratory status can be closely monitored.

At Ob Hospitalist Group, our body of evidence from our large national footprint has informed the development of standard sets of protocols for delivery complications such as preeclampsia and postpartum hemorrhage, as well as a cesarean section reduction toolkit to combat medically unnecessary cesarean sections. OB hospitalists therefore can assist with refining COVID-19 protocols specifically for the L&D setting, using evidence-based data to tailor protocols to address public health emergencies as they evolve.

The second way that Ob hospitalists can support their colleagues is by covering L&D 24/7 so that community obstetricians can focus on other pressing medical needs. From our experience with other outbreaks such as severe acute respiratory syndrome (SARS) and influenza, we anticipate that obstetricians in private practice likely will have their hands full juggling a regular patient load, fielding calls from concerned patients, and caring for infected or ill patients who are being treated in an outpatient setting. Adding to that plate the need to rush to the hospital to clinically assess a patient for COVID-19 or for a delivery only compounds stress and exhaustion. At Ob Hospitalist Group, our hospitalist programs provide coverage and support to community obstetricians until they can arrive at the hospital or when the woman has no assigned obstetrician, reducing the pressure on community obstetricians to rush through their schedules.

Diagnostic and pharmaceutical companies are collaborating with public health officials to expedite diagnostic testing staff, hospital treatment capacity, vaccines, and even early therapies that may help to minimize severity. But right now, as clinicians work to protect their vulnerable patients, a close collaboration between community obstetricians and Ob hospitalists will help to keep patients and health care personnel safe and healthy – a goal that should apply not only to public health crises, but to the provision of maternal care every day.
 

Dr. Simon is chief medical officer at Ob Hospitalist Group (OBHG), is a board-certified ob.gyn., and former head of the department of obstetrics and gynecology for a U.S. hospital. He has no relevant conflicts of interest or financial disclosures. Email him at obnews@mdedge.com.

With the novel coronavirus (COVID-19) monopolizing the news cycle, fear and misinformation are at an all-time high. Public health officials and physicians are accelerating education outreach to the public to address misinformation, and identify and care for patients who may have been exposed to the virus.

In times of public health crises, pregnant women have unique and pressing concerns about their personal health and the health of their unborn children. While not often mentioned in major news coverage, obstetricians play a critical role during health crises because of their uniquely personal role with patients during all stages of pregnancy, providing this vulnerable population with the most up-to-date information and following the latest guidelines for recommended care.

Unfortunately, COVID-19 is breaking unfamiliar new ground. We know that pregnant women are at higher risk for viral infection – annually, influenza is a grim reminder that pregnant women are more immunocompromised than the general public – but we do not yet have data to confirm or refute that pregnant women have a higher susceptibility to COVID-19 than the rest of the adult population. We also do not know enough about COVID-19 transmission, including whether the virus can cross the transplacental barrier to affect a fetus, or whether it can be transmitted through breast milk. 

As private practice community obstetricians work to protect their patients during this public health crisis, Ob hospitalists can play an important role in supporting them in the provision of patient care. 

First, Ob hospitalists are highly-trained specialists who can help ensure that pregnant patients who seek care at the hospital – either with viral symptoms or with separate pregnancy-related concerns – are protected during triage until the treating community obstetrician can take the reins.

When a pregnant woman presents at a hospital, in most cases she will bypass the ED and instead be sent directly to the labor and delivery (L&D) unit. During a viral outbreak, there are two major concerns with this approach. For one thing, it means an immunocompromised woman is being sent through the hospital to get to L&D, and along the path, is exposed to every airborne pathogen in the facility (and, if she is already infected, exposes others along the way). In addition, in hospitals without an Ob hospitalist on site, the patient generally is not immediately triaged by a physician, physician’s assistant, or nurse practitioner upon arrival because those clinicians are not consistently on site in L&D.

In times of viral pandemics, new approaches are warranted. For hospitals with contracted L&D management with hospitalists, hospitalists work closely with department heads to implement protocols loosely based on the Emergency Severity Index (ESI) model established by the Agency for Healthcare Research and Quality. Just as the ESI algorithm guides clinical stratification of patients, in times of reported viral outbreaks, L&D should consider triage of all pregnant women at higher levels of acuity, regardless of presentation status. In particular, if they show clinical symptoms, they should be masked, accompanied to the L&D unit by protected personnel, separated from other patients in areas of forced proximity such as hallways and elevators, and triaged in a secure single-patient room with a closed door (ideally at negative pressure relative to the surrounding areas). 

If the patient has traveled to an area of outbreak, reports exposure to travelers who have visited high-risk areas, has had contact with individuals who tested positive for COVID-19, or exhibits any clinical symptoms of COVID-19 (fever, dry cough, fatigue, etc.), her care management should adhere to standing hospital emergency protocols. Following consultation with the assigned community obstetrician, the Ob hospitalist and hospital staff should contact their local/state health departments immediately for all cases of patients who show symptoms to determine if the patient meets requirements for a person under investigation (PUI) for COVID-19. The state/local health department will work with clinicians to collect, store, and ship clinical specimens appropriately. Very ill patients may need to be treated in an intensive care setting where respiratory status can be closely monitored.

At Ob Hospitalist Group, our body of evidence from our large national footprint has informed the development of standard sets of protocols for delivery complications such as preeclampsia and postpartum hemorrhage, as well as a cesarean section reduction toolkit to combat medically unnecessary cesarean sections. OB hospitalists therefore can assist with refining COVID-19 protocols specifically for the L&D setting, using evidence-based data to tailor protocols to address public health emergencies as they evolve.

The second way that Ob hospitalists can support their colleagues is by covering L&D 24/7 so that community obstetricians can focus on other pressing medical needs. From our experience with other outbreaks such as severe acute respiratory syndrome (SARS) and influenza, we anticipate that obstetricians in private practice likely will have their hands full juggling a regular patient load, fielding calls from concerned patients, and caring for infected or ill patients who are being treated in an outpatient setting. Adding to that plate the need to rush to the hospital to clinically assess a patient for COVID-19 or for a delivery only compounds stress and exhaustion. At Ob Hospitalist Group, our hospitalist programs provide coverage and support to community obstetricians until they can arrive at the hospital or when the woman has no assigned obstetrician, reducing the pressure on community obstetricians to rush through their schedules.

Diagnostic and pharmaceutical companies are collaborating with public health officials to expedite diagnostic testing staff, hospital treatment capacity, vaccines, and even early therapies that may help to minimize severity. But right now, as clinicians work to protect their vulnerable patients, a close collaboration between community obstetricians and Ob hospitalists will help to keep patients and health care personnel safe and healthy – a goal that should apply not only to public health crises, but to the provision of maternal care every day.
 

Dr. Simon is chief medical officer at Ob Hospitalist Group (OBHG), is a board-certified ob.gyn., and former head of the department of obstetrics and gynecology for a U.S. hospital. He has no relevant conflicts of interest or financial disclosures. Email him at obnews@mdedge.com.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.⁶ Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.⁷ All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.⁶ Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.⁷ All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.⁶ Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.⁷ All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

Two very different specialties, obstetrics (O) and gynecology (G), were fused into one in 1889. It is difficult to conceive that, with the expansion of both specialties in knowledge, procedures, and subspecialties, they still remain as one after 130 years. The American College of Obstetricians and Gynecologists was founded in 1952, and after 68 years no major changes have been made to accept or incorporate that there is a need to consider O and G as two different specialties.

Obstetrics and gynecology are the only specialties dedicated exclusively to women but with a very different purpose: the O is for reproduction, the G is for prevention and management of genital diseases. The specialties of O and G are so different the only thing in common is the patient.

It is time to separate the O from the G.
 

Are we training surgically competent residents?

No, we are not. There is an adequate volume for training and practice in O with close to 3.8 million births a year (the number cited by the Centers for Disease Control and Prevention in 2018). Not surprisingly, there is a need for trainees and also for practitioners in rural areas. As a result, the surgical training and practice in G is not optimal. If the number of hysterectomies was even near that of deliveries, there would be an adequate volume for everyone in training and in practice. But this is not the case.

The Accreditation Council for Graduate Medical Education (ACGME) mandates OG residents to graduate with a minimum of 70 minimally invasive hysterectomies (MIH), including laparoscopic (LH), vaginal (VH), and laparoscopic vaginally assisted (LAVH). In 2017, 51% of graduating residents fell below the minimum of 70 MIH.¹ Because the learning curve of LH ranges from 30 to 80 cases,² it is not surprising most residents feel surgically inadequate at graduation to function independently.
 

Increased procedures and technologies with reduced training hours

Let’s look at hysterectomies. From two techniques, vaginal and abdominal, they have expanded to LH, LAVH, robotic, single-site LH, single-site robotic, and recently single-port robotic. In addition, different and new technologies for hysteroscopy and myomectomy procedures have been developed.

All these operations are supposed to be part of any training program as ACGME demands “OG residents must be able to competently perform all medical, diagnostic, and surgical procedures considered essential for the area of practice.”³ In addition, primary care has been added to OG residency training: “Primary health care management from adolescence through reproductive age to midlife and beyond is integral to any ob.gyn.’s practice” and “Obstetrician-gynecologists are viewed by some entities as being primary care physicians for women, especially as coordinators of care among most reproductive-aged women,” according to ACOG.⁴

All this with reduced training hours.

The number of training hours a week has been reduced to 80, while it used to be over 100 hours. If you do the math, 20 fewer hours a week for 4 years amounts to 4,240 hours, equivalent to 180 days, equal to 6 months.

The present residents must learn more with fewer hours of training. Graduating residents must pass a written and an oral exam for certification and with this are approved to enter the operating room and operate on women without a surgical skills test.
 

 

A simple test shows that elimination of the O for 1 year improves laparoscopic performance

We compared the time to perform three basic laparoscopic skills by fourth-year OG residents with that of fellows at the end of their first year in a minimally invasive G fellowship.⁵ The mean time for the residents completing the three tasks within the allotted time was 16 minutes, compared with 3.5 minutes for fellows: a four times faster performance.

Are there enough patients to maintain surgical skills after residency?

No, there are not.

Consider the following reality after residency. Decreasing number of surgeries and increasing numbers of OGs results in what you have already guessed: a lower surgical volume per OG.

Since 1979, the number of G surgeries has decreased by almost half (46%) while the number of OGs has doubled (54%) resulting in an 81% decrease of number of surgeries per OG, from 132 in 1979 to 25 in 2007.⁶ For hysterectomies, there has been a continuous yearly decline per G from 28 in 1980 to 9.8 in 2007 and to 8.5 in 2010.^7,8

Would any mother feel comfortable having an obstetrician for her pregnancy and delivery performing only 8.5 deliveries a year?
 

Where do we go from here?

Separate the training and practice of O and G, an initiative already started in some residency programs and in some institutions in the United States. The O and the G both include a medical and a surgical practice.

We need to start accepting there is a need for different practices: medical O, medical G, surgical O, and surgical G. It is not new, it is already happening, it is the case in our institution since inception, and it is expanding across the country because it is needed. Graduating residents recognize this need as noticed by the increasing number seeking subspecialty training, from 7% in 2000 to 19.5% in 2012.⁴

Will this require some patients to drive away from home to obtain the best possible care? Yes. It is not a new concept, and it already is occurring for patients traveling to specialized centers away from home for certain conditions. In some countries, the practice is restricted to only a few centers. In Sweden, for instance, patients diagnosed with gynecologic cancer must travel to one of only seven centers subspecialized in gynecologic malignancies.
 

Conclusion

We need to start someday. We already are late after 130 years. We need to provide optimal care for women. They are our mothers. They deserve it. Let the O deliver O care, let the G provide G care, and we will reap improved results.

Dr. Magrina is with the department of medical and surgical gynecology at the Mayo Clinic in Phoenix. The author has no conflict of interest or financial involvement with this manuscript.

References

1. Am J Obstet Gynecol. 2019 Nov 22. doi: 10.1016/j.ajog.2019.11.1258.

2. Clin Obstet Gynecol. 2011 Sep;54(3):376-81.

3. Accreditation Council for Graduate Medical Education. Program requirements for GME in Obstetrics and Gynecology 2017.

4. “The obstetrician-gynecologist workforce in the United States: Facts, figures, and implications, 2017” (Washington, D.C.: ACOG, 2017).

5. J Minim Invasive Gynecol. 2008 Jul-Aug;15(4):410-3.

6. J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):501-3.

7. National Health Statistics Report. Hysterectomy in the U.S. and oophorectomy 1979-2007. http://www.cdc.gov/nchs/products/nhsr.htm.

8. The Healthcare Cost and Utilization Project – Nationwide Inpatient Sample: Agency for Health Care Research Quality. 2013.






 

Two very different specialties, obstetrics (O) and gynecology (G), were fused into one in 1889. It is difficult to conceive that, with the expansion of both specialties in knowledge, procedures, and subspecialties, they still remain as one after 130 years. The American College of Obstetricians and Gynecologists was founded in 1952, and after 68 years no major changes have been made to accept or incorporate that there is a need to consider O and G as two different specialties.

Obstetrics and gynecology are the only specialties dedicated exclusively to women but with a very different purpose: the O is for reproduction, the G is for prevention and management of genital diseases. The specialties of O and G are so different the only thing in common is the patient.

It is time to separate the O from the G.
 

Are we training surgically competent residents?

No, we are not. There is an adequate volume for training and practice in O with close to 3.8 million births a year (the number cited by the Centers for Disease Control and Prevention in 2018). Not surprisingly, there is a need for trainees and also for practitioners in rural areas. As a result, the surgical training and practice in G is not optimal. If the number of hysterectomies was even near that of deliveries, there would be an adequate volume for everyone in training and in practice. But this is not the case.

The Accreditation Council for Graduate Medical Education (ACGME) mandates OG residents to graduate with a minimum of 70 minimally invasive hysterectomies (MIH), including laparoscopic (LH), vaginal (VH), and laparoscopic vaginally assisted (LAVH). In 2017, 51% of graduating residents fell below the minimum of 70 MIH.¹ Because the learning curve of LH ranges from 30 to 80 cases,² it is not surprising most residents feel surgically inadequate at graduation to function independently.
 

Increased procedures and technologies with reduced training hours

Let’s look at hysterectomies. From two techniques, vaginal and abdominal, they have expanded to LH, LAVH, robotic, single-site LH, single-site robotic, and recently single-port robotic. In addition, different and new technologies for hysteroscopy and myomectomy procedures have been developed.

All these operations are supposed to be part of any training program as ACGME demands “OG residents must be able to competently perform all medical, diagnostic, and surgical procedures considered essential for the area of practice.”³ In addition, primary care has been added to OG residency training: “Primary health care management from adolescence through reproductive age to midlife and beyond is integral to any ob.gyn.’s practice” and “Obstetrician-gynecologists are viewed by some entities as being primary care physicians for women, especially as coordinators of care among most reproductive-aged women,” according to ACOG.⁴

All this with reduced training hours.

The number of training hours a week has been reduced to 80, while it used to be over 100 hours. If you do the math, 20 fewer hours a week for 4 years amounts to 4,240 hours, equivalent to 180 days, equal to 6 months.

The present residents must learn more with fewer hours of training. Graduating residents must pass a written and an oral exam for certification and with this are approved to enter the operating room and operate on women without a surgical skills test.
 

 

A simple test shows that elimination of the O for 1 year improves laparoscopic performance

We compared the time to perform three basic laparoscopic skills by fourth-year OG residents with that of fellows at the end of their first year in a minimally invasive G fellowship.⁵ The mean time for the residents completing the three tasks within the allotted time was 16 minutes, compared with 3.5 minutes for fellows: a four times faster performance.

Are there enough patients to maintain surgical skills after residency?

No, there are not.

Consider the following reality after residency. Decreasing number of surgeries and increasing numbers of OGs results in what you have already guessed: a lower surgical volume per OG.

Since 1979, the number of G surgeries has decreased by almost half (46%) while the number of OGs has doubled (54%) resulting in an 81% decrease of number of surgeries per OG, from 132 in 1979 to 25 in 2007.⁶ For hysterectomies, there has been a continuous yearly decline per G from 28 in 1980 to 9.8 in 2007 and to 8.5 in 2010.^7,8

Would any mother feel comfortable having an obstetrician for her pregnancy and delivery performing only 8.5 deliveries a year?
 

Where do we go from here?

Separate the training and practice of O and G, an initiative already started in some residency programs and in some institutions in the United States. The O and the G both include a medical and a surgical practice.

We need to start accepting there is a need for different practices: medical O, medical G, surgical O, and surgical G. It is not new, it is already happening, it is the case in our institution since inception, and it is expanding across the country because it is needed. Graduating residents recognize this need as noticed by the increasing number seeking subspecialty training, from 7% in 2000 to 19.5% in 2012.⁴

Will this require some patients to drive away from home to obtain the best possible care? Yes. It is not a new concept, and it already is occurring for patients traveling to specialized centers away from home for certain conditions. In some countries, the practice is restricted to only a few centers. In Sweden, for instance, patients diagnosed with gynecologic cancer must travel to one of only seven centers subspecialized in gynecologic malignancies.
 

Conclusion

We need to start someday. We already are late after 130 years. We need to provide optimal care for women. They are our mothers. They deserve it. Let the O deliver O care, let the G provide G care, and we will reap improved results.

Dr. Magrina is with the department of medical and surgical gynecology at the Mayo Clinic in Phoenix. The author has no conflict of interest or financial involvement with this manuscript.

References

1. Am J Obstet Gynecol. 2019 Nov 22. doi: 10.1016/j.ajog.2019.11.1258.

2. Clin Obstet Gynecol. 2011 Sep;54(3):376-81.

3. Accreditation Council for Graduate Medical Education. Program requirements for GME in Obstetrics and Gynecology 2017.

4. “The obstetrician-gynecologist workforce in the United States: Facts, figures, and implications, 2017” (Washington, D.C.: ACOG, 2017).

5. J Minim Invasive Gynecol. 2008 Jul-Aug;15(4):410-3.

6. J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):501-3.

7. National Health Statistics Report. Hysterectomy in the U.S. and oophorectomy 1979-2007. http://www.cdc.gov/nchs/products/nhsr.htm.

8. The Healthcare Cost and Utilization Project – Nationwide Inpatient Sample: Agency for Health Care Research Quality. 2013.






 

Two very different specialties, obstetrics (O) and gynecology (G), were fused into one in 1889. It is difficult to conceive that, with the expansion of both specialties in knowledge, procedures, and subspecialties, they still remain as one after 130 years. The American College of Obstetricians and Gynecologists was founded in 1952, and after 68 years no major changes have been made to accept or incorporate that there is a need to consider O and G as two different specialties.

Obstetrics and gynecology are the only specialties dedicated exclusively to women but with a very different purpose: the O is for reproduction, the G is for prevention and management of genital diseases. The specialties of O and G are so different the only thing in common is the patient.

It is time to separate the O from the G.
 

Are we training surgically competent residents?

No, we are not. There is an adequate volume for training and practice in O with close to 3.8 million births a year (the number cited by the Centers for Disease Control and Prevention in 2018). Not surprisingly, there is a need for trainees and also for practitioners in rural areas. As a result, the surgical training and practice in G is not optimal. If the number of hysterectomies was even near that of deliveries, there would be an adequate volume for everyone in training and in practice. But this is not the case.

The Accreditation Council for Graduate Medical Education (ACGME) mandates OG residents to graduate with a minimum of 70 minimally invasive hysterectomies (MIH), including laparoscopic (LH), vaginal (VH), and laparoscopic vaginally assisted (LAVH). In 2017, 51% of graduating residents fell below the minimum of 70 MIH.¹ Because the learning curve of LH ranges from 30 to 80 cases,² it is not surprising most residents feel surgically inadequate at graduation to function independently.
 

Increased procedures and technologies with reduced training hours

Let’s look at hysterectomies. From two techniques, vaginal and abdominal, they have expanded to LH, LAVH, robotic, single-site LH, single-site robotic, and recently single-port robotic. In addition, different and new technologies for hysteroscopy and myomectomy procedures have been developed.

All these operations are supposed to be part of any training program as ACGME demands “OG residents must be able to competently perform all medical, diagnostic, and surgical procedures considered essential for the area of practice.”³ In addition, primary care has been added to OG residency training: “Primary health care management from adolescence through reproductive age to midlife and beyond is integral to any ob.gyn.’s practice” and “Obstetrician-gynecologists are viewed by some entities as being primary care physicians for women, especially as coordinators of care among most reproductive-aged women,” according to ACOG.⁴

All this with reduced training hours.

The number of training hours a week has been reduced to 80, while it used to be over 100 hours. If you do the math, 20 fewer hours a week for 4 years amounts to 4,240 hours, equivalent to 180 days, equal to 6 months.

The present residents must learn more with fewer hours of training. Graduating residents must pass a written and an oral exam for certification and with this are approved to enter the operating room and operate on women without a surgical skills test.
 

 

A simple test shows that elimination of the O for 1 year improves laparoscopic performance

We compared the time to perform three basic laparoscopic skills by fourth-year OG residents with that of fellows at the end of their first year in a minimally invasive G fellowship.⁵ The mean time for the residents completing the three tasks within the allotted time was 16 minutes, compared with 3.5 minutes for fellows: a four times faster performance.

Are there enough patients to maintain surgical skills after residency?

No, there are not.

Consider the following reality after residency. Decreasing number of surgeries and increasing numbers of OGs results in what you have already guessed: a lower surgical volume per OG.

Since 1979, the number of G surgeries has decreased by almost half (46%) while the number of OGs has doubled (54%) resulting in an 81% decrease of number of surgeries per OG, from 132 in 1979 to 25 in 2007.⁶ For hysterectomies, there has been a continuous yearly decline per G from 28 in 1980 to 9.8 in 2007 and to 8.5 in 2010.^7,8

Would any mother feel comfortable having an obstetrician for her pregnancy and delivery performing only 8.5 deliveries a year?
 

Where do we go from here?

Separate the training and practice of O and G, an initiative already started in some residency programs and in some institutions in the United States. The O and the G both include a medical and a surgical practice.

We need to start accepting there is a need for different practices: medical O, medical G, surgical O, and surgical G. It is not new, it is already happening, it is the case in our institution since inception, and it is expanding across the country because it is needed. Graduating residents recognize this need as noticed by the increasing number seeking subspecialty training, from 7% in 2000 to 19.5% in 2012.⁴

Will this require some patients to drive away from home to obtain the best possible care? Yes. It is not a new concept, and it already is occurring for patients traveling to specialized centers away from home for certain conditions. In some countries, the practice is restricted to only a few centers. In Sweden, for instance, patients diagnosed with gynecologic cancer must travel to one of only seven centers subspecialized in gynecologic malignancies.
 

Conclusion

We need to start someday. We already are late after 130 years. We need to provide optimal care for women. They are our mothers. They deserve it. Let the O deliver O care, let the G provide G care, and we will reap improved results.

Dr. Magrina is with the department of medical and surgical gynecology at the Mayo Clinic in Phoenix. The author has no conflict of interest or financial involvement with this manuscript.

References

1. Am J Obstet Gynecol. 2019 Nov 22. doi: 10.1016/j.ajog.2019.11.1258.

2. Clin Obstet Gynecol. 2011 Sep;54(3):376-81.

3. Accreditation Council for Graduate Medical Education. Program requirements for GME in Obstetrics and Gynecology 2017.

4. “The obstetrician-gynecologist workforce in the United States: Facts, figures, and implications, 2017” (Washington, D.C.: ACOG, 2017).

5. J Minim Invasive Gynecol. 2008 Jul-Aug;15(4):410-3.

6. J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):501-3.

7. National Health Statistics Report. Hysterectomy in the U.S. and oophorectomy 1979-2007. http://www.cdc.gov/nchs/products/nhsr.htm.

8. The Healthcare Cost and Utilization Project – Nationwide Inpatient Sample: Agency for Health Care Research Quality. 2013.






 

Prematurity remains the leading cause of neonatal morbidity and mortality, accounting for $26 billion a year in immediate costs, despite the implementation in obstetrics of a host of risk stratification algorithms and strategies for risk reduction, including the use of some medications.

It now is questionable whether injectable 17-alpha hydroxyprogesterone caproate (Makena) truly is efficacious in women who’ve had a prior spontaneous preterm birth (sPTB) – a Food and Drug Administration advisory committee last year recommended withdrawing it from the market based on results of an FDA confirmatory study. Even if the drug were efficacious, only a small percentage of the women who have an sPTB have had a prior one. The majority of sPTB occurs among women without such a history.

Vaginal progesterone appears to confer some protection in women found to have a short cervix during the second trimester, but this approach also has limited reach: Only 9% of women with sPTB had an antecedent short cervix in a 2017 study.¹ Like a history of sPTB, screening for short cervical length is a potentially helpful strategy for risk reduction, but it is not a strategy that will significantly impact the overall rate of prematurity.

We’ve fallen short in our goals to significantly reduce the public health impact of prematurity partly because we still do not understand the exact pathways and mechanisms by which sPTB occurs. The main working paradigm for myself and many other researchers over the past 2 decades has centered on infection in the uterus triggering inflammation, followed by cervical remodeling and ripening. Research in animal models, as well as human clinical trials targeting various infections and inflammation, have led to some insights and discoveries, but no successful interventions.

In the past decade, however, our research framework for understanding sPTB incorporates new questions about immunologic, microbiological, and molecular/cellular events that happen in the cervicovaginal space. We’ve learned more about the cervicovaginal microbiota, and most recently, our research at the University of Pennsylvania has elucidated the role that nonoptimal bacteria play in disrupting the cervical endothelial barrier and initiating the process of cervical remodeling that likely precedes sPTB.

We now know that there is an association between cervicovaginal microbial communities, immune responses, and sPTB. We also know that this association is stronger in black women and may help explain some of the observed racial disparities in sPTB. Although more research is needed to determine specific therapeutic strategies, new doors are open.
 

Host immune-microbial interactions

This new research paradigm has involved stepping back and asking basic questions, such as, what do we really know about the cervicovaginal space? In actuality, we know very little. We know little about the immune function of the vaginal and cervical epithelial cells in pregnancy, for instance, and there is a large gap in knowledge regarding the biomechanics of the cervix – a remarkable organ that can change shape and function in a matter of minutes. Studies on the biomechanics of the cervix during pregnancy and in labor are still in their infancy.

However, lessons can be drawn from research on inflammatory bowel disease and other disorders involving the gut. In the gastrointestinal tract, epithelial cells have been found to act as sentinels, forming a mucosal barrier against bacterial pathogens and secreting various immune factors. Research in this field also has shown that microbes living in the gut produce metabolites; that these microbial metabolites may be the key messengers from the microbial communities to the epithelial barrier; and that the microbes, microbial metabolites, and immune responses are responsible for triggering inflammatory processes in the tissues underneath.

In 2011, Jacques Ravel, PhD, who was part of the National Institutes of Health’s Human Microbiome Project, characterized the vaginal microbiome of reproductive-age women for the first time.² His paper classified the vaginal microbial communities of approximately 400 asymptomatic women of various ethnicities into five “community state types” (CSTs) based on the predominant bacteria found in the cervicovaginal space.³

On the heels of his research, Dr. Ravel and I launched an NIH-funded study involving a prospective cohort of 2,000 women with singleton pregnancies – the Motherhood & Microbiome cohort – to look at the cervicovaginal microbiota, the local immune response, and the risk of sPTB.⁴ Cervicovaginal samples were collected at 16-20 weeks’ gestation and during two subsequent clinical visits. From this cohort, which was composed mostly of African American women (74.5%), we conducted a nested case-controlled study of 103 cases of sPTB and 432 women who delivered at term, matched for race.

We carefully adjudicated the deliveries in our 2,000-person cohort so that we homed in on sPTB as opposed to preterm births that are medically indicated for reasons such as fetal distress or preeclampsia. (Several prior studies looking at the associations between the cervicovaginal microbiome had a heterogeneous phenotyping of PTB that made it hard to draw definitive conclusions.)

Our focus in assessing the microbiome and immunologic profiles was on the samples collected at the earliest time points in pregnancy because we hoped to detect a “signature” that could predict an outcome months later. Indeed, we found that the nonoptimal microbiota, known in microbiological terms as CST IV, was associated with about a 150% increased risk of sPTB. This community comprises a dominant array of anaerobic bacteria and a paucity of Lactobacillus species.

We also found that a larger proportion of African American women, compared with non–African American women, had this nonoptimal microbiota early in pregnancy (40% vs. 15%), which is consistent with previous studies in pregnancy and nonpregnancy showing lower levels of Lactobacillus species in the cervicovaginal microbiome of African American women.

Even more interesting was the finding that, although the rate of sPTB was higher in African American women and the effect of CST IV on sPTB was stronger in these women, the risk of sPTB couldn’t be explained solely by the presence of CST IV. Some women with this nonoptimal microbiome delivered at term, whereas others with more optimal microbiome types had sPTBs. This suggests that other factors contribute to African American women having a nonoptimal microbiota and being especially predisposed to sPTB.

Through the study’s immunologic profiling, we found a significant difference in the cervicovaginal levels of an immune factor, beta-defensin 2, between African American women who delivered at term and those who had a sPTB. Women who had a sPTB, even those who had higher levels of Lactobacillus species, had lower levels of beta-defensin 2. This association was not found in non–African American women.

Beta-defensin 2 is a host-derived antimicrobial peptide that, like other antimicrobial peptides, works at epithelial-mucosal barriers to combat bacteria; we have knowledge of its action from research on the gut, as well as some studies of the vaginal space in nonpregnant women that have focused on sexually transmitted infections.

Most exciting for us was the finding that higher levels of beta-defensin 2 appeared to lower the risk of sPTB in women who had a nonoptimal cervicovaginal microbiota. There’s an interplay between the host and the microbiota, in other words, and it’s one that could be essential to manipulate as we seek to reduce sPTB.
 

 

The cervical epithelial barrier

In the laboratory, meanwhile, we are learning how certain microbes are mechanistically involved in the pathogenesis of sPTB. Research over the last decade has suggested that disruption or breakdown of the cervical epithelial barrier drives cervical remodeling processes that precede sPTB. The question now is, do cervicovaginal bacteria associated with sPTB, or a nonoptimal cervicovaginal microbiota, cause disruption of the vaginal and cervical epithelial barrier – and how?

Using an in vitro model system, we found that Mobiluncus curtisii/mulieris, the bacterial taxa with the strongest association with sPTB in our Motherhood & Microbiome cohort and one that has long been associated with bacterial vaginosis, had a plethora of effects. It increased cell permeability and the expression of inflammatory mediators associated with cervical epithelial breakdown, and it altered expression of microRNAs that have been associated with sPTB in human studies.

Our study on Mobiluncus has served as proof of concept to us that, not only is the bacteria associated with sPTB, but that there are multiple mechanisms by which it can disrupt the cervicovaginal barrier and lead to cervical remodeling.⁵

The findings echo previous in vitro research on Gardnerella vaginalis, another anaerobic bacterium that has been associated with bacterial vaginosis and adverse obstetric outcomes, including sPTB.⁶ Using similar models, we found that G. vaginalis disrupts the cervical epithelial barrier through diverse mechanisms including the cleavage of certain proteins, the up-regulation of proinflammatory immune mediators, and altered gene expression.

Lactobacillus crispatus, on the other hand, conferred protection to the cervical epithelial barrier in this study by mitigating various G. vaginalis–induced effects.

Learning more about host-microbe interactions and the role of microbial metabolites in these interactions, as well as the role of altered gene expression in cervical function, will help us to more fully understand the biological mechanisms regulating cervicovaginal epithelial cells. At this point, we know that, as in the gut, bacteria commonly found in the cervicovaginal space play a significant role in regulating the function of epithelial cells (in both optimal and nonoptimal microbiota), and that various bacteria associated with sPTB contribute to poor outcomes by breaking down the cervical epithelium.
 

Therapeutic implications

Our growing knowledge of the cervicovaginal microbiota does not yet support screening or any particular interventions. We don’t know, for instance, that administering probiotics or prebiotics orally or vaginally will have any effect on rates of sPTB.

Ongoing research at all levels holds promise, however, for the development of diagnostics to identify women at risk for sPTB, and for the development of therapeutic strategies that aim to modify the microbiome and/or modify the immune response. We know from other areas of medicine that there are realistic ways to modulate the immune response and/or microbiota in a system to alter risk.

We need to more thoroughly understand the risk of particular microbiota and immune response factors – and how they vary by race and ethnicity – and we need to study the cervicovaginal microbiota of women before and during pregnancy to learn whether there is something about pregnancy or even about intercourse that can change one’s microbiome to a less favorable state.

It may well be possible in the near future to identify high-risk states of nonoptimal microbiota before conception – microbiota that, in and of themselves, may not be pathogenic but that become detrimental during pregnancy – and it should be possible to screen women early in pregnancy for microbial or immune signatures or both.

The question often arises in medicine of the validity of screening without having achieved certainty about treatments. However, in obstetrics, where we have different levels of care and the ability to personalize monitoring and care, identifying those at greatest risk still has value. Ultimately, with enough investment in all levels of research (basic, translational, and clinical), we can develop interventions and therapeutics that address a biologically plausible mechanism of sPTB and, as a result, achieve significant reductions in the rate of prematurity.

Dr. Elovitz is the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health, vice chair of translational research, and director of the Maternal and Child Health Research Center, department of obstetrics and gynecology, at the University of Pennsylvania, Philadelphia. She disclosed holding a patent on a method to determine risk of preterm birth that relates to the microbiome. Email her at obnews@mdedge.com.

References

1. JAMA. 2017 Mar 14;317(10):1047-56.

2. NIH Human Microbiome Project. https://hmpdacc.org/.

3. PNAS. 2011 Mar 15;108 (Supplement 1):4680-7.

4. Nat Commun. 2019 Mar 21. doi: 10.1038/s41467-019-09285-9.

5. Anaerobe. 2019 Nov 21. doi: 10.1016/j.anaerobe.2019.102127.

6. Front Microbiol. 2018 Oct 8. doi: 10.3389/fmicb.2018.02181.

Prematurity remains the leading cause of neonatal morbidity and mortality, accounting for $26 billion a year in immediate costs, despite the implementation in obstetrics of a host of risk stratification algorithms and strategies for risk reduction, including the use of some medications.

It now is questionable whether injectable 17-alpha hydroxyprogesterone caproate (Makena) truly is efficacious in women who’ve had a prior spontaneous preterm birth (sPTB) – a Food and Drug Administration advisory committee last year recommended withdrawing it from the market based on results of an FDA confirmatory study. Even if the drug were efficacious, only a small percentage of the women who have an sPTB have had a prior one. The majority of sPTB occurs among women without such a history.

Vaginal progesterone appears to confer some protection in women found to have a short cervix during the second trimester, but this approach also has limited reach: Only 9% of women with sPTB had an antecedent short cervix in a 2017 study.¹ Like a history of sPTB, screening for short cervical length is a potentially helpful strategy for risk reduction, but it is not a strategy that will significantly impact the overall rate of prematurity.

We’ve fallen short in our goals to significantly reduce the public health impact of prematurity partly because we still do not understand the exact pathways and mechanisms by which sPTB occurs. The main working paradigm for myself and many other researchers over the past 2 decades has centered on infection in the uterus triggering inflammation, followed by cervical remodeling and ripening. Research in animal models, as well as human clinical trials targeting various infections and inflammation, have led to some insights and discoveries, but no successful interventions.

In the past decade, however, our research framework for understanding sPTB incorporates new questions about immunologic, microbiological, and molecular/cellular events that happen in the cervicovaginal space. We’ve learned more about the cervicovaginal microbiota, and most recently, our research at the University of Pennsylvania has elucidated the role that nonoptimal bacteria play in disrupting the cervical endothelial barrier and initiating the process of cervical remodeling that likely precedes sPTB.

We now know that there is an association between cervicovaginal microbial communities, immune responses, and sPTB. We also know that this association is stronger in black women and may help explain some of the observed racial disparities in sPTB. Although more research is needed to determine specific therapeutic strategies, new doors are open.
 

Host immune-microbial interactions

This new research paradigm has involved stepping back and asking basic questions, such as, what do we really know about the cervicovaginal space? In actuality, we know very little. We know little about the immune function of the vaginal and cervical epithelial cells in pregnancy, for instance, and there is a large gap in knowledge regarding the biomechanics of the cervix – a remarkable organ that can change shape and function in a matter of minutes. Studies on the biomechanics of the cervix during pregnancy and in labor are still in their infancy.

However, lessons can be drawn from research on inflammatory bowel disease and other disorders involving the gut. In the gastrointestinal tract, epithelial cells have been found to act as sentinels, forming a mucosal barrier against bacterial pathogens and secreting various immune factors. Research in this field also has shown that microbes living in the gut produce metabolites; that these microbial metabolites may be the key messengers from the microbial communities to the epithelial barrier; and that the microbes, microbial metabolites, and immune responses are responsible for triggering inflammatory processes in the tissues underneath.

In 2011, Jacques Ravel, PhD, who was part of the National Institutes of Health’s Human Microbiome Project, characterized the vaginal microbiome of reproductive-age women for the first time.² His paper classified the vaginal microbial communities of approximately 400 asymptomatic women of various ethnicities into five “community state types” (CSTs) based on the predominant bacteria found in the cervicovaginal space.³

On the heels of his research, Dr. Ravel and I launched an NIH-funded study involving a prospective cohort of 2,000 women with singleton pregnancies – the Motherhood & Microbiome cohort – to look at the cervicovaginal microbiota, the local immune response, and the risk of sPTB.⁴ Cervicovaginal samples were collected at 16-20 weeks’ gestation and during two subsequent clinical visits. From this cohort, which was composed mostly of African American women (74.5%), we conducted a nested case-controlled study of 103 cases of sPTB and 432 women who delivered at term, matched for race.

We carefully adjudicated the deliveries in our 2,000-person cohort so that we homed in on sPTB as opposed to preterm births that are medically indicated for reasons such as fetal distress or preeclampsia. (Several prior studies looking at the associations between the cervicovaginal microbiome had a heterogeneous phenotyping of PTB that made it hard to draw definitive conclusions.)

Our focus in assessing the microbiome and immunologic profiles was on the samples collected at the earliest time points in pregnancy because we hoped to detect a “signature” that could predict an outcome months later. Indeed, we found that the nonoptimal microbiota, known in microbiological terms as CST IV, was associated with about a 150% increased risk of sPTB. This community comprises a dominant array of anaerobic bacteria and a paucity of Lactobacillus species.

We also found that a larger proportion of African American women, compared with non–African American women, had this nonoptimal microbiota early in pregnancy (40% vs. 15%), which is consistent with previous studies in pregnancy and nonpregnancy showing lower levels of Lactobacillus species in the cervicovaginal microbiome of African American women.

Even more interesting was the finding that, although the rate of sPTB was higher in African American women and the effect of CST IV on sPTB was stronger in these women, the risk of sPTB couldn’t be explained solely by the presence of CST IV. Some women with this nonoptimal microbiome delivered at term, whereas others with more optimal microbiome types had sPTBs. This suggests that other factors contribute to African American women having a nonoptimal microbiota and being especially predisposed to sPTB.

Through the study’s immunologic profiling, we found a significant difference in the cervicovaginal levels of an immune factor, beta-defensin 2, between African American women who delivered at term and those who had a sPTB. Women who had a sPTB, even those who had higher levels of Lactobacillus species, had lower levels of beta-defensin 2. This association was not found in non–African American women.

Beta-defensin 2 is a host-derived antimicrobial peptide that, like other antimicrobial peptides, works at epithelial-mucosal barriers to combat bacteria; we have knowledge of its action from research on the gut, as well as some studies of the vaginal space in nonpregnant women that have focused on sexually transmitted infections.

Most exciting for us was the finding that higher levels of beta-defensin 2 appeared to lower the risk of sPTB in women who had a nonoptimal cervicovaginal microbiota. There’s an interplay between the host and the microbiota, in other words, and it’s one that could be essential to manipulate as we seek to reduce sPTB.
 

 

The cervical epithelial barrier

In the laboratory, meanwhile, we are learning how certain microbes are mechanistically involved in the pathogenesis of sPTB. Research over the last decade has suggested that disruption or breakdown of the cervical epithelial barrier drives cervical remodeling processes that precede sPTB. The question now is, do cervicovaginal bacteria associated with sPTB, or a nonoptimal cervicovaginal microbiota, cause disruption of the vaginal and cervical epithelial barrier – and how?

Using an in vitro model system, we found that Mobiluncus curtisii/mulieris, the bacterial taxa with the strongest association with sPTB in our Motherhood & Microbiome cohort and one that has long been associated with bacterial vaginosis, had a plethora of effects. It increased cell permeability and the expression of inflammatory mediators associated with cervical epithelial breakdown, and it altered expression of microRNAs that have been associated with sPTB in human studies.

Our study on Mobiluncus has served as proof of concept to us that, not only is the bacteria associated with sPTB, but that there are multiple mechanisms by which it can disrupt the cervicovaginal barrier and lead to cervical remodeling.⁵

The findings echo previous in vitro research on Gardnerella vaginalis, another anaerobic bacterium that has been associated with bacterial vaginosis and adverse obstetric outcomes, including sPTB.⁶ Using similar models, we found that G. vaginalis disrupts the cervical epithelial barrier through diverse mechanisms including the cleavage of certain proteins, the up-regulation of proinflammatory immune mediators, and altered gene expression.

Lactobacillus crispatus, on the other hand, conferred protection to the cervical epithelial barrier in this study by mitigating various G. vaginalis–induced effects.

Learning more about host-microbe interactions and the role of microbial metabolites in these interactions, as well as the role of altered gene expression in cervical function, will help us to more fully understand the biological mechanisms regulating cervicovaginal epithelial cells. At this point, we know that, as in the gut, bacteria commonly found in the cervicovaginal space play a significant role in regulating the function of epithelial cells (in both optimal and nonoptimal microbiota), and that various bacteria associated with sPTB contribute to poor outcomes by breaking down the cervical epithelium.
 

Therapeutic implications

Our growing knowledge of the cervicovaginal microbiota does not yet support screening or any particular interventions. We don’t know, for instance, that administering probiotics or prebiotics orally or vaginally will have any effect on rates of sPTB.

Ongoing research at all levels holds promise, however, for the development of diagnostics to identify women at risk for sPTB, and for the development of therapeutic strategies that aim to modify the microbiome and/or modify the immune response. We know from other areas of medicine that there are realistic ways to modulate the immune response and/or microbiota in a system to alter risk.

We need to more thoroughly understand the risk of particular microbiota and immune response factors – and how they vary by race and ethnicity – and we need to study the cervicovaginal microbiota of women before and during pregnancy to learn whether there is something about pregnancy or even about intercourse that can change one’s microbiome to a less favorable state.

It may well be possible in the near future to identify high-risk states of nonoptimal microbiota before conception – microbiota that, in and of themselves, may not be pathogenic but that become detrimental during pregnancy – and it should be possible to screen women early in pregnancy for microbial or immune signatures or both.

The question often arises in medicine of the validity of screening without having achieved certainty about treatments. However, in obstetrics, where we have different levels of care and the ability to personalize monitoring and care, identifying those at greatest risk still has value. Ultimately, with enough investment in all levels of research (basic, translational, and clinical), we can develop interventions and therapeutics that address a biologically plausible mechanism of sPTB and, as a result, achieve significant reductions in the rate of prematurity.

Dr. Elovitz is the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health, vice chair of translational research, and director of the Maternal and Child Health Research Center, department of obstetrics and gynecology, at the University of Pennsylvania, Philadelphia. She disclosed holding a patent on a method to determine risk of preterm birth that relates to the microbiome. Email her at obnews@mdedge.com.

References

1. JAMA. 2017 Mar 14;317(10):1047-56.

2. NIH Human Microbiome Project. https://hmpdacc.org/.

3. PNAS. 2011 Mar 15;108 (Supplement 1):4680-7.

4. Nat Commun. 2019 Mar 21. doi: 10.1038/s41467-019-09285-9.

5. Anaerobe. 2019 Nov 21. doi: 10.1016/j.anaerobe.2019.102127.

6. Front Microbiol. 2018 Oct 8. doi: 10.3389/fmicb.2018.02181.

Prematurity remains the leading cause of neonatal morbidity and mortality, accounting for $26 billion a year in immediate costs, despite the implementation in obstetrics of a host of risk stratification algorithms and strategies for risk reduction, including the use of some medications.

It now is questionable whether injectable 17-alpha hydroxyprogesterone caproate (Makena) truly is efficacious in women who’ve had a prior spontaneous preterm birth (sPTB) – a Food and Drug Administration advisory committee last year recommended withdrawing it from the market based on results of an FDA confirmatory study. Even if the drug were efficacious, only a small percentage of the women who have an sPTB have had a prior one. The majority of sPTB occurs among women without such a history.

Vaginal progesterone appears to confer some protection in women found to have a short cervix during the second trimester, but this approach also has limited reach: Only 9% of women with sPTB had an antecedent short cervix in a 2017 study.¹ Like a history of sPTB, screening for short cervical length is a potentially helpful strategy for risk reduction, but it is not a strategy that will significantly impact the overall rate of prematurity.

We’ve fallen short in our goals to significantly reduce the public health impact of prematurity partly because we still do not understand the exact pathways and mechanisms by which sPTB occurs. The main working paradigm for myself and many other researchers over the past 2 decades has centered on infection in the uterus triggering inflammation, followed by cervical remodeling and ripening. Research in animal models, as well as human clinical trials targeting various infections and inflammation, have led to some insights and discoveries, but no successful interventions.

In the past decade, however, our research framework for understanding sPTB incorporates new questions about immunologic, microbiological, and molecular/cellular events that happen in the cervicovaginal space. We’ve learned more about the cervicovaginal microbiota, and most recently, our research at the University of Pennsylvania has elucidated the role that nonoptimal bacteria play in disrupting the cervical endothelial barrier and initiating the process of cervical remodeling that likely precedes sPTB.

We now know that there is an association between cervicovaginal microbial communities, immune responses, and sPTB. We also know that this association is stronger in black women and may help explain some of the observed racial disparities in sPTB. Although more research is needed to determine specific therapeutic strategies, new doors are open.
 

Host immune-microbial interactions

This new research paradigm has involved stepping back and asking basic questions, such as, what do we really know about the cervicovaginal space? In actuality, we know very little. We know little about the immune function of the vaginal and cervical epithelial cells in pregnancy, for instance, and there is a large gap in knowledge regarding the biomechanics of the cervix – a remarkable organ that can change shape and function in a matter of minutes. Studies on the biomechanics of the cervix during pregnancy and in labor are still in their infancy.

However, lessons can be drawn from research on inflammatory bowel disease and other disorders involving the gut. In the gastrointestinal tract, epithelial cells have been found to act as sentinels, forming a mucosal barrier against bacterial pathogens and secreting various immune factors. Research in this field also has shown that microbes living in the gut produce metabolites; that these microbial metabolites may be the key messengers from the microbial communities to the epithelial barrier; and that the microbes, microbial metabolites, and immune responses are responsible for triggering inflammatory processes in the tissues underneath.

In 2011, Jacques Ravel, PhD, who was part of the National Institutes of Health’s Human Microbiome Project, characterized the vaginal microbiome of reproductive-age women for the first time.² His paper classified the vaginal microbial communities of approximately 400 asymptomatic women of various ethnicities into five “community state types” (CSTs) based on the predominant bacteria found in the cervicovaginal space.³

On the heels of his research, Dr. Ravel and I launched an NIH-funded study involving a prospective cohort of 2,000 women with singleton pregnancies – the Motherhood & Microbiome cohort – to look at the cervicovaginal microbiota, the local immune response, and the risk of sPTB.⁴ Cervicovaginal samples were collected at 16-20 weeks’ gestation and during two subsequent clinical visits. From this cohort, which was composed mostly of African American women (74.5%), we conducted a nested case-controlled study of 103 cases of sPTB and 432 women who delivered at term, matched for race.

We carefully adjudicated the deliveries in our 2,000-person cohort so that we homed in on sPTB as opposed to preterm births that are medically indicated for reasons such as fetal distress or preeclampsia. (Several prior studies looking at the associations between the cervicovaginal microbiome had a heterogeneous phenotyping of PTB that made it hard to draw definitive conclusions.)

Our focus in assessing the microbiome and immunologic profiles was on the samples collected at the earliest time points in pregnancy because we hoped to detect a “signature” that could predict an outcome months later. Indeed, we found that the nonoptimal microbiota, known in microbiological terms as CST IV, was associated with about a 150% increased risk of sPTB. This community comprises a dominant array of anaerobic bacteria and a paucity of Lactobacillus species.

We also found that a larger proportion of African American women, compared with non–African American women, had this nonoptimal microbiota early in pregnancy (40% vs. 15%), which is consistent with previous studies in pregnancy and nonpregnancy showing lower levels of Lactobacillus species in the cervicovaginal microbiome of African American women.

Even more interesting was the finding that, although the rate of sPTB was higher in African American women and the effect of CST IV on sPTB was stronger in these women, the risk of sPTB couldn’t be explained solely by the presence of CST IV. Some women with this nonoptimal microbiome delivered at term, whereas others with more optimal microbiome types had sPTBs. This suggests that other factors contribute to African American women having a nonoptimal microbiota and being especially predisposed to sPTB.

Through the study’s immunologic profiling, we found a significant difference in the cervicovaginal levels of an immune factor, beta-defensin 2, between African American women who delivered at term and those who had a sPTB. Women who had a sPTB, even those who had higher levels of Lactobacillus species, had lower levels of beta-defensin 2. This association was not found in non–African American women.

Beta-defensin 2 is a host-derived antimicrobial peptide that, like other antimicrobial peptides, works at epithelial-mucosal barriers to combat bacteria; we have knowledge of its action from research on the gut, as well as some studies of the vaginal space in nonpregnant women that have focused on sexually transmitted infections.

Most exciting for us was the finding that higher levels of beta-defensin 2 appeared to lower the risk of sPTB in women who had a nonoptimal cervicovaginal microbiota. There’s an interplay between the host and the microbiota, in other words, and it’s one that could be essential to manipulate as we seek to reduce sPTB.
 

 

The cervical epithelial barrier

In the laboratory, meanwhile, we are learning how certain microbes are mechanistically involved in the pathogenesis of sPTB. Research over the last decade has suggested that disruption or breakdown of the cervical epithelial barrier drives cervical remodeling processes that precede sPTB. The question now is, do cervicovaginal bacteria associated with sPTB, or a nonoptimal cervicovaginal microbiota, cause disruption of the vaginal and cervical epithelial barrier – and how?

Using an in vitro model system, we found that Mobiluncus curtisii/mulieris, the bacterial taxa with the strongest association with sPTB in our Motherhood & Microbiome cohort and one that has long been associated with bacterial vaginosis, had a plethora of effects. It increased cell permeability and the expression of inflammatory mediators associated with cervical epithelial breakdown, and it altered expression of microRNAs that have been associated with sPTB in human studies.

Our study on Mobiluncus has served as proof of concept to us that, not only is the bacteria associated with sPTB, but that there are multiple mechanisms by which it can disrupt the cervicovaginal barrier and lead to cervical remodeling.⁵

The findings echo previous in vitro research on Gardnerella vaginalis, another anaerobic bacterium that has been associated with bacterial vaginosis and adverse obstetric outcomes, including sPTB.⁶ Using similar models, we found that G. vaginalis disrupts the cervical epithelial barrier through diverse mechanisms including the cleavage of certain proteins, the up-regulation of proinflammatory immune mediators, and altered gene expression.

Lactobacillus crispatus, on the other hand, conferred protection to the cervical epithelial barrier in this study by mitigating various G. vaginalis–induced effects.

Learning more about host-microbe interactions and the role of microbial metabolites in these interactions, as well as the role of altered gene expression in cervical function, will help us to more fully understand the biological mechanisms regulating cervicovaginal epithelial cells. At this point, we know that, as in the gut, bacteria commonly found in the cervicovaginal space play a significant role in regulating the function of epithelial cells (in both optimal and nonoptimal microbiota), and that various bacteria associated with sPTB contribute to poor outcomes by breaking down the cervical epithelium.
 

Therapeutic implications

Our growing knowledge of the cervicovaginal microbiota does not yet support screening or any particular interventions. We don’t know, for instance, that administering probiotics or prebiotics orally or vaginally will have any effect on rates of sPTB.

Ongoing research at all levels holds promise, however, for the development of diagnostics to identify women at risk for sPTB, and for the development of therapeutic strategies that aim to modify the microbiome and/or modify the immune response. We know from other areas of medicine that there are realistic ways to modulate the immune response and/or microbiota in a system to alter risk.

We need to more thoroughly understand the risk of particular microbiota and immune response factors – and how they vary by race and ethnicity – and we need to study the cervicovaginal microbiota of women before and during pregnancy to learn whether there is something about pregnancy or even about intercourse that can change one’s microbiome to a less favorable state.

It may well be possible in the near future to identify high-risk states of nonoptimal microbiota before conception – microbiota that, in and of themselves, may not be pathogenic but that become detrimental during pregnancy – and it should be possible to screen women early in pregnancy for microbial or immune signatures or both.

The question often arises in medicine of the validity of screening without having achieved certainty about treatments. However, in obstetrics, where we have different levels of care and the ability to personalize monitoring and care, identifying those at greatest risk still has value. Ultimately, with enough investment in all levels of research (basic, translational, and clinical), we can develop interventions and therapeutics that address a biologically plausible mechanism of sPTB and, as a result, achieve significant reductions in the rate of prematurity.

Dr. Elovitz is the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health, vice chair of translational research, and director of the Maternal and Child Health Research Center, department of obstetrics and gynecology, at the University of Pennsylvania, Philadelphia. She disclosed holding a patent on a method to determine risk of preterm birth that relates to the microbiome. Email her at obnews@mdedge.com.

References

1. JAMA. 2017 Mar 14;317(10):1047-56.

2. NIH Human Microbiome Project. https://hmpdacc.org/.

3. PNAS. 2011 Mar 15;108 (Supplement 1):4680-7.

4. Nat Commun. 2019 Mar 21. doi: 10.1038/s41467-019-09285-9.

5. Anaerobe. 2019 Nov 21. doi: 10.1016/j.anaerobe.2019.102127.

6. Front Microbiol. 2018 Oct 8. doi: 10.3389/fmicb.2018.02181.