Perspectives

I don’t know how successful you have been at getting your adolescent patients to follow your suggestions, but I would guess that my batting average was in the low 100s. Even when I try stepping off my soapbox to involve the patient in a nonjudgmental dialogue, my successes pale in comparison to my failures.

Vladimir Vladimirov/E+/Getty Images

Just looking at our national statistics for obesity, it’s pretty obvious that we are all doing a pretty rotten job of modifying our patients behaviors. You could point to a few encouraging numbers but they are few and far between. You could claim correctly that by the time a child reaches preschool, the die is already cast, throw up your arms, and not even raise the subject of diet with your overweight teenage patients.

A recent article in the journal Appetite hints at a group of strategies for molding patient behavior that so far have gotten very little attention from physicians (“Do perceived norms of social media users eating habits and preferences predict our own food consumption and BMI?” Appetite. 2020 Jan 18. doi: 10.1016/j.appet.2020.104611). Researchers at the department of psychology at Ashton University in Birmingham, England, surveyed more than 350 college-age students asking them about the dietary preference of their Facebook contacts and their own dietary habits. What the investigators found was that respondents who perceived their peers ate a healthy diet ate a healthier diet. Conversely, if the respondents thought their social media contacts ate junk food, they reported eating more of an unhealthy diet themselves.

In other words, it appears that, through social media, we have the potential to influence the eating habits of our patients’ peers. Before we get too excited, it should be pointed out that this study from England wasn’t of a long enough duration to demonstrate an effect on body mass index. And another study of 176 children recently published in Pediatrics found that while influencer marketing of unhealthy foods increased children’s immediate food intake, the equivalent marketing of healthy foods had no effect (“Social influencer marketing and children’s food intake: A randomized trial.” Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2554).

Not being terribly aware of the whos, whats, and wheres of influencers, I did a little bit of Internet searching at the Influencer Marketing hub and learned that influencers comes in all shapes and sizes, from “nanoinfluencers” who have acknowledged expertise and a very small Internet following numbering as few as a hundred to “megainfluencers” who have more than a million followers and might charge large entities a million dollars for a single post. The influencer’s content could appear as a blog, a YouTube video, a podcast, or simply a social media post.

The field of influencer marketing is new and growing exponentially. We would be wise as a group and as individuals to learn as much as we can about how we can use influencers to promote healthy behaviors. This initiative could come in the form of an office dedicated to Influencer Marketing created by the American Academy of Pediatrics. That group could search for megainfluencers who might be funded by the academy. But it also could develop a handbook for individual practitioners and groups to help them identify nano- and micro- (1,000-40,000 followers) influencers in their own practices.

You probably don’t ask your patients about their social media habits other than to caution them about time management. Maybe it’s time to dig a little deeper. You may find that you have a potent influencer hidden in your practice. She or he might just be willing to spread a good word or two for you.
 

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 [email protected].

I don’t know how successful you have been at getting your adolescent patients to follow your suggestions, but I would guess that my batting average was in the low 100s. Even when I try stepping off my soapbox to involve the patient in a nonjudgmental dialogue, my successes pale in comparison to my failures.

Vladimir Vladimirov/E+/Getty Images

Just looking at our national statistics for obesity, it’s pretty obvious that we are all doing a pretty rotten job of modifying our patients behaviors. You could point to a few encouraging numbers but they are few and far between. You could claim correctly that by the time a child reaches preschool, the die is already cast, throw up your arms, and not even raise the subject of diet with your overweight teenage patients.

A recent article in the journal Appetite hints at a group of strategies for molding patient behavior that so far have gotten very little attention from physicians (“Do perceived norms of social media users eating habits and preferences predict our own food consumption and BMI?” Appetite. 2020 Jan 18. doi: 10.1016/j.appet.2020.104611). Researchers at the department of psychology at Ashton University in Birmingham, England, surveyed more than 350 college-age students asking them about the dietary preference of their Facebook contacts and their own dietary habits. What the investigators found was that respondents who perceived their peers ate a healthy diet ate a healthier diet. Conversely, if the respondents thought their social media contacts ate junk food, they reported eating more of an unhealthy diet themselves.

In other words, it appears that, through social media, we have the potential to influence the eating habits of our patients’ peers. Before we get too excited, it should be pointed out that this study from England wasn’t of a long enough duration to demonstrate an effect on body mass index. And another study of 176 children recently published in Pediatrics found that while influencer marketing of unhealthy foods increased children’s immediate food intake, the equivalent marketing of healthy foods had no effect (“Social influencer marketing and children’s food intake: A randomized trial.” Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2554).

Not being terribly aware of the whos, whats, and wheres of influencers, I did a little bit of Internet searching at the Influencer Marketing hub and learned that influencers comes in all shapes and sizes, from “nanoinfluencers” who have acknowledged expertise and a very small Internet following numbering as few as a hundred to “megainfluencers” who have more than a million followers and might charge large entities a million dollars for a single post. The influencer’s content could appear as a blog, a YouTube video, a podcast, or simply a social media post.

The field of influencer marketing is new and growing exponentially. We would be wise as a group and as individuals to learn as much as we can about how we can use influencers to promote healthy behaviors. This initiative could come in the form of an office dedicated to Influencer Marketing created by the American Academy of Pediatrics. That group could search for megainfluencers who might be funded by the academy. But it also could develop a handbook for individual practitioners and groups to help them identify nano- and micro- (1,000-40,000 followers) influencers in their own practices.

You probably don’t ask your patients about their social media habits other than to caution them about time management. Maybe it’s time to dig a little deeper. You may find that you have a potent influencer hidden in your practice. She or he might just be willing to spread a good word or two for you.
 

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 [email protected].

I don’t know how successful you have been at getting your adolescent patients to follow your suggestions, but I would guess that my batting average was in the low 100s. Even when I try stepping off my soapbox to involve the patient in a nonjudgmental dialogue, my successes pale in comparison to my failures.

Vladimir Vladimirov/E+/Getty Images

Just looking at our national statistics for obesity, it’s pretty obvious that we are all doing a pretty rotten job of modifying our patients behaviors. You could point to a few encouraging numbers but they are few and far between. You could claim correctly that by the time a child reaches preschool, the die is already cast, throw up your arms, and not even raise the subject of diet with your overweight teenage patients.

A recent article in the journal Appetite hints at a group of strategies for molding patient behavior that so far have gotten very little attention from physicians (“Do perceived norms of social media users eating habits and preferences predict our own food consumption and BMI?” Appetite. 2020 Jan 18. doi: 10.1016/j.appet.2020.104611). Researchers at the department of psychology at Ashton University in Birmingham, England, surveyed more than 350 college-age students asking them about the dietary preference of their Facebook contacts and their own dietary habits. What the investigators found was that respondents who perceived their peers ate a healthy diet ate a healthier diet. Conversely, if the respondents thought their social media contacts ate junk food, they reported eating more of an unhealthy diet themselves.

In other words, it appears that, through social media, we have the potential to influence the eating habits of our patients’ peers. Before we get too excited, it should be pointed out that this study from England wasn’t of a long enough duration to demonstrate an effect on body mass index. And another study of 176 children recently published in Pediatrics found that while influencer marketing of unhealthy foods increased children’s immediate food intake, the equivalent marketing of healthy foods had no effect (“Social influencer marketing and children’s food intake: A randomized trial.” Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2554).

Not being terribly aware of the whos, whats, and wheres of influencers, I did a little bit of Internet searching at the Influencer Marketing hub and learned that influencers comes in all shapes and sizes, from “nanoinfluencers” who have acknowledged expertise and a very small Internet following numbering as few as a hundred to “megainfluencers” who have more than a million followers and might charge large entities a million dollars for a single post. The influencer’s content could appear as a blog, a YouTube video, a podcast, or simply a social media post.

The field of influencer marketing is new and growing exponentially. We would be wise as a group and as individuals to learn as much as we can about how we can use influencers to promote healthy behaviors. This initiative could come in the form of an office dedicated to Influencer Marketing created by the American Academy of Pediatrics. That group could search for megainfluencers who might be funded by the academy. But it also could develop a handbook for individual practitioners and groups to help them identify nano- and micro- (1,000-40,000 followers) influencers in their own practices.

You probably don’t ask your patients about their social media habits other than to caution them about time management. Maybe it’s time to dig a little deeper. You may find that you have a potent influencer hidden in your practice. She or he might just be willing to spread a good word or two for you.
 

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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

• 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 [email protected].

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

• 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 [email protected].

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

• 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 [email protected].

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.

The United States Declaration of Independence is widely known for the words that begin its second paragraph:

We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.

Those basic rights are accessible and exercised by all healthy US citizens, but for many individuals with psychiatric disorders, those inalienable rights may be elusive. Consider how they are compromised by untreated psychiatric illness.

Life. This is the most basic right. In the United States, healthy individuals cherish being alive, and many take it for granted, unlike the residents of nondemocratic countries, where persons may be killed by dictators for political or other reasons (Stalin and Hitler murdered millions of innocent people). In the past, persons with mental illness were considered possessed by demons and were killed or burned at the stake (as in the Middle Ages). But unfortunately, the current major risk for the loss of life among psychiatric patients is the patients themselves. Suicidal urges, attempts, and completions are of epidemic proportions and continue to rise every year. Our patients end their own lives because their illness prompts them to relinquish their life and to embrace untimely death. And once life is lost, all other rights are abdicated. Suicide attempts are common among patients who are diagnosed with bipolar disorder, major depressive disorder, schizophrenia, anxiety, obsessive-compulsive disorder (OCD), posttraumatic stress disorder, and borderline personality disorder. Sometimes, suicide is unintentional, such as when a patient with a substance use disorder inadvertently overdoses (as in the contemporary opioid epidemic) or ingests drugs laced with a deadly substance. For many untreated patients, life can be so fragile, tenuous, and tragically brief.

Liberty. Healthy citizens in the United States (and other democratic countries) have many liberties: where to live, what to do, where to move, what to say, what to believe, who to assemble with, what to eat or drink, whom to befriend, whom to marry, whether or not to procreate, and what to wear. They can choose to be an activist for any cause, no matter how quaint, or to disfigure their bodies with tattoos or piercings.

In contrast, the liberties of individuals with a psychiatric disorder can be compromised. In fact, patients’ liberties can be seriously shackled by their illness. A person with untreated schizophrenia can be enslaved by fixed irrational beliefs that may constrain their choices or determine how they live or relate to others. Command hallucinations can dictate what a patient should or mustn’t do. Poor reality testing detrimentally limits the options of a person with psychosis. A lack of insight deprives a patient with schizophrenia from rational decision-making. Self-neglect leads to physical, mental, and social deterioration.

For persons with depression, the range of liberties is shattered by social withdrawal, overwhelming guilt, sense of worthlessness, dismal hopelessness, doleful ruminations, and loss of appetite or sleep. The only rights that people with depression may exercise is to injure their body or end their life.

Think also of patients with OCD, who are subjugated by their ongoing obsessions or compulsive rituals; think of those with panic disorder who are unable to leave their home due to agoraphobia or cannot drive freely because of fears related to bridges or tunnels; think of persons who are enchained by their addiction and oppressed by the craving for drugs, food, or gambling. There are few meaningful liberties left for all such patients.

Continue to: Happiness

Happiness. I often wonder if most Americans these days are pursuing pleasure rather than happiness, seeking the momentary thrill and gratification instead of long-lasting happiness and joy. But persons with psychiatric brain disorders have great difficulty pursuing either pleasure or happiness. Anhedonia is a common symptom in schizophrenia and depression, depriving patients from experiencing enjoyable activities (ie, having fun) as they used to do before they got sick. Persons with anxiety have such emotional turmoil, it is hard for them to experience pleasure or happiness when feelings of impending doom permeates their souls. Persons with an addictive disorder are coerced to seek their substance for a momentary reward, only to spend a much longer time craving and seeking their substance of choice again and again. On the other end of the spectrum, for persons with mania, the excessive pursuit of high-risk pleasures can have grave consequences or embarrassment after they recover.

Happiness for patients with mental illness is possible only when they emerge from their illness and are “liberated” from the symptoms that disrupt their lives. As psychiatrists, we don’t just evaluate and treat patients with psychiatric illness—we restore their liberties and ability to pursue happiness and enjoy small pleasures.

The motto on the seal of the American University of Beirut, which I attended in my youth, is “That they may have life, and to have it abundantly.” As I have grown older and wiser, I have come to realize the true meaning of that motto. Life is a right we take for granted, but without it, we cannot exercise the various liberties, or be able to pursue happiness. I exercised my right to become a psychiatrist, and that provided me with lifelong happiness and satisfaction, especially when I prevent the loss of life of my patients, restore their liberty by ridding them of illness, and resurrect their ability to experience pleasure and pursue happiness.

The United States Declaration of Independence is widely known for the words that begin its second paragraph:

We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.

Those basic rights are accessible and exercised by all healthy US citizens, but for many individuals with psychiatric disorders, those inalienable rights may be elusive. Consider how they are compromised by untreated psychiatric illness.

Life. This is the most basic right. In the United States, healthy individuals cherish being alive, and many take it for granted, unlike the residents of nondemocratic countries, where persons may be killed by dictators for political or other reasons (Stalin and Hitler murdered millions of innocent people). In the past, persons with mental illness were considered possessed by demons and were killed or burned at the stake (as in the Middle Ages). But unfortunately, the current major risk for the loss of life among psychiatric patients is the patients themselves. Suicidal urges, attempts, and completions are of epidemic proportions and continue to rise every year. Our patients end their own lives because their illness prompts them to relinquish their life and to embrace untimely death. And once life is lost, all other rights are abdicated. Suicide attempts are common among patients who are diagnosed with bipolar disorder, major depressive disorder, schizophrenia, anxiety, obsessive-compulsive disorder (OCD), posttraumatic stress disorder, and borderline personality disorder. Sometimes, suicide is unintentional, such as when a patient with a substance use disorder inadvertently overdoses (as in the contemporary opioid epidemic) or ingests drugs laced with a deadly substance. For many untreated patients, life can be so fragile, tenuous, and tragically brief.

Liberty. Healthy citizens in the United States (and other democratic countries) have many liberties: where to live, what to do, where to move, what to say, what to believe, who to assemble with, what to eat or drink, whom to befriend, whom to marry, whether or not to procreate, and what to wear. They can choose to be an activist for any cause, no matter how quaint, or to disfigure their bodies with tattoos or piercings.

In contrast, the liberties of individuals with a psychiatric disorder can be compromised. In fact, patients’ liberties can be seriously shackled by their illness. A person with untreated schizophrenia can be enslaved by fixed irrational beliefs that may constrain their choices or determine how they live or relate to others. Command hallucinations can dictate what a patient should or mustn’t do. Poor reality testing detrimentally limits the options of a person with psychosis. A lack of insight deprives a patient with schizophrenia from rational decision-making. Self-neglect leads to physical, mental, and social deterioration.

For persons with depression, the range of liberties is shattered by social withdrawal, overwhelming guilt, sense of worthlessness, dismal hopelessness, doleful ruminations, and loss of appetite or sleep. The only rights that people with depression may exercise is to injure their body or end their life.

Think also of patients with OCD, who are subjugated by their ongoing obsessions or compulsive rituals; think of those with panic disorder who are unable to leave their home due to agoraphobia or cannot drive freely because of fears related to bridges or tunnels; think of persons who are enchained by their addiction and oppressed by the craving for drugs, food, or gambling. There are few meaningful liberties left for all such patients.

Continue to: Happiness

Happiness. I often wonder if most Americans these days are pursuing pleasure rather than happiness, seeking the momentary thrill and gratification instead of long-lasting happiness and joy. But persons with psychiatric brain disorders have great difficulty pursuing either pleasure or happiness. Anhedonia is a common symptom in schizophrenia and depression, depriving patients from experiencing enjoyable activities (ie, having fun) as they used to do before they got sick. Persons with anxiety have such emotional turmoil, it is hard for them to experience pleasure or happiness when feelings of impending doom permeates their souls. Persons with an addictive disorder are coerced to seek their substance for a momentary reward, only to spend a much longer time craving and seeking their substance of choice again and again. On the other end of the spectrum, for persons with mania, the excessive pursuit of high-risk pleasures can have grave consequences or embarrassment after they recover.

Happiness for patients with mental illness is possible only when they emerge from their illness and are “liberated” from the symptoms that disrupt their lives. As psychiatrists, we don’t just evaluate and treat patients with psychiatric illness—we restore their liberties and ability to pursue happiness and enjoy small pleasures.

The motto on the seal of the American University of Beirut, which I attended in my youth, is “That they may have life, and to have it abundantly.” As I have grown older and wiser, I have come to realize the true meaning of that motto. Life is a right we take for granted, but without it, we cannot exercise the various liberties, or be able to pursue happiness. I exercised my right to become a psychiatrist, and that provided me with lifelong happiness and satisfaction, especially when I prevent the loss of life of my patients, restore their liberty by ridding them of illness, and resurrect their ability to experience pleasure and pursue happiness.

The United States Declaration of Independence is widely known for the words that begin its second paragraph:

We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.

Those basic rights are accessible and exercised by all healthy US citizens, but for many individuals with psychiatric disorders, those inalienable rights may be elusive. Consider how they are compromised by untreated psychiatric illness.

Life. This is the most basic right. In the United States, healthy individuals cherish being alive, and many take it for granted, unlike the residents of nondemocratic countries, where persons may be killed by dictators for political or other reasons (Stalin and Hitler murdered millions of innocent people). In the past, persons with mental illness were considered possessed by demons and were killed or burned at the stake (as in the Middle Ages). But unfortunately, the current major risk for the loss of life among psychiatric patients is the patients themselves. Suicidal urges, attempts, and completions are of epidemic proportions and continue to rise every year. Our patients end their own lives because their illness prompts them to relinquish their life and to embrace untimely death. And once life is lost, all other rights are abdicated. Suicide attempts are common among patients who are diagnosed with bipolar disorder, major depressive disorder, schizophrenia, anxiety, obsessive-compulsive disorder (OCD), posttraumatic stress disorder, and borderline personality disorder. Sometimes, suicide is unintentional, such as when a patient with a substance use disorder inadvertently overdoses (as in the contemporary opioid epidemic) or ingests drugs laced with a deadly substance. For many untreated patients, life can be so fragile, tenuous, and tragically brief.

Liberty. Healthy citizens in the United States (and other democratic countries) have many liberties: where to live, what to do, where to move, what to say, what to believe, who to assemble with, what to eat or drink, whom to befriend, whom to marry, whether or not to procreate, and what to wear. They can choose to be an activist for any cause, no matter how quaint, or to disfigure their bodies with tattoos or piercings.

In contrast, the liberties of individuals with a psychiatric disorder can be compromised. In fact, patients’ liberties can be seriously shackled by their illness. A person with untreated schizophrenia can be enslaved by fixed irrational beliefs that may constrain their choices or determine how they live or relate to others. Command hallucinations can dictate what a patient should or mustn’t do. Poor reality testing detrimentally limits the options of a person with psychosis. A lack of insight deprives a patient with schizophrenia from rational decision-making. Self-neglect leads to physical, mental, and social deterioration.

For persons with depression, the range of liberties is shattered by social withdrawal, overwhelming guilt, sense of worthlessness, dismal hopelessness, doleful ruminations, and loss of appetite or sleep. The only rights that people with depression may exercise is to injure their body or end their life.

Think also of patients with OCD, who are subjugated by their ongoing obsessions or compulsive rituals; think of those with panic disorder who are unable to leave their home due to agoraphobia or cannot drive freely because of fears related to bridges or tunnels; think of persons who are enchained by their addiction and oppressed by the craving for drugs, food, or gambling. There are few meaningful liberties left for all such patients.

Continue to: Happiness

Happiness. I often wonder if most Americans these days are pursuing pleasure rather than happiness, seeking the momentary thrill and gratification instead of long-lasting happiness and joy. But persons with psychiatric brain disorders have great difficulty pursuing either pleasure or happiness. Anhedonia is a common symptom in schizophrenia and depression, depriving patients from experiencing enjoyable activities (ie, having fun) as they used to do before they got sick. Persons with anxiety have such emotional turmoil, it is hard for them to experience pleasure or happiness when feelings of impending doom permeates their souls. Persons with an addictive disorder are coerced to seek their substance for a momentary reward, only to spend a much longer time craving and seeking their substance of choice again and again. On the other end of the spectrum, for persons with mania, the excessive pursuit of high-risk pleasures can have grave consequences or embarrassment after they recover.

Happiness for patients with mental illness is possible only when they emerge from their illness and are “liberated” from the symptoms that disrupt their lives. As psychiatrists, we don’t just evaluate and treat patients with psychiatric illness—we restore their liberties and ability to pursue happiness and enjoy small pleasures.

The motto on the seal of the American University of Beirut, which I attended in my youth, is “That they may have life, and to have it abundantly.” As I have grown older and wiser, I have come to realize the true meaning of that motto. Life is a right we take for granted, but without it, we cannot exercise the various liberties, or be able to pursue happiness. I exercised my right to become a psychiatrist, and that provided me with lifelong happiness and satisfaction, especially when I prevent the loss of life of my patients, restore their liberty by ridding them of illness, and resurrect their ability to experience pleasure and pursue happiness.

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 [email protected].

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 [email protected].

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 [email protected].

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.

Preventing infant mortality remains a significant challenge for ob.gyns. Despite the availability of a multitude of preventive and treatment options and some of the best possible medical care offered in the world, the United States lags behind many other developed and developing countries in its rate of infant deaths, which was an estimated 5.8 deaths per 1,000 live births in 2017. We can, and must, do better.

One of the major contributing factors to infant mortality is preterm birth. Defined as birth occurring prior to 37 weeks’ gestation, preterm birth is associated with a myriad of severe neonatal sequelae: low birth weight, bacterial sepsis, neonatal hemorrhage, and respiratory distress syndrome, among others. Therefore, many within the clinical and biomedical research spheres recognize that preventing preterm birth means reducing infant deaths.

However, therein lies the conundrum. We know very little about what causes preterm birth, which renders the current therapeutic strategies – such as use of progesterone supplements or cerclage placement – good for some but not all patients. It is thus vital to continue research to unravel the underlying mechanisms of preterm birth.

A promising area of investigation is the field of microbiome research, which has made great strides in advancing our awareness of the critical role of the millions of organisms living on and within us in maintaining health and fighting disease. For example, we now realize that eradicating all the commensals in our gastrointestinal tract has unintended and very negative consequences and, for patients whose good bacteria have been eliminated, fecal transplant is a therapeutic option. Therefore, it stands to reason that the microbes found in the vagina contribute significantly to women’s overall reproductive health.

The publication of the groundbreaking study characterizing the vaginal microbiome species in reproductive-age women opened new avenues of research into how these organisms contribute to women’s health. Importantly, this work, led initially by Jacques Ravel, PhD, a professor in the department of microbiology & immunology and associate director of the Institute for Genome Sciences at the University of Maryland School of Medicine, has spawned additional investigations into the potential role of the vaginal microbiome in preterm birth.

To provide some insight into the research around how the microorganisms in the vagina may induce or prevent preterm birth is our guest author, Michal A. Elovitz, MD, 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.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Preventing infant mortality remains a significant challenge for ob.gyns. Despite the availability of a multitude of preventive and treatment options and some of the best possible medical care offered in the world, the United States lags behind many other developed and developing countries in its rate of infant deaths, which was an estimated 5.8 deaths per 1,000 live births in 2017. We can, and must, do better.

One of the major contributing factors to infant mortality is preterm birth. Defined as birth occurring prior to 37 weeks’ gestation, preterm birth is associated with a myriad of severe neonatal sequelae: low birth weight, bacterial sepsis, neonatal hemorrhage, and respiratory distress syndrome, among others. Therefore, many within the clinical and biomedical research spheres recognize that preventing preterm birth means reducing infant deaths.

However, therein lies the conundrum. We know very little about what causes preterm birth, which renders the current therapeutic strategies – such as use of progesterone supplements or cerclage placement – good for some but not all patients. It is thus vital to continue research to unravel the underlying mechanisms of preterm birth.

A promising area of investigation is the field of microbiome research, which has made great strides in advancing our awareness of the critical role of the millions of organisms living on and within us in maintaining health and fighting disease. For example, we now realize that eradicating all the commensals in our gastrointestinal tract has unintended and very negative consequences and, for patients whose good bacteria have been eliminated, fecal transplant is a therapeutic option. Therefore, it stands to reason that the microbes found in the vagina contribute significantly to women’s overall reproductive health.

The publication of the groundbreaking study characterizing the vaginal microbiome species in reproductive-age women opened new avenues of research into how these organisms contribute to women’s health. Importantly, this work, led initially by Jacques Ravel, PhD, a professor in the department of microbiology & immunology and associate director of the Institute for Genome Sciences at the University of Maryland School of Medicine, has spawned additional investigations into the potential role of the vaginal microbiome in preterm birth.

To provide some insight into the research around how the microorganisms in the vagina may induce or prevent preterm birth is our guest author, Michal A. Elovitz, MD, 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.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Preventing infant mortality remains a significant challenge for ob.gyns. Despite the availability of a multitude of preventive and treatment options and some of the best possible medical care offered in the world, the United States lags behind many other developed and developing countries in its rate of infant deaths, which was an estimated 5.8 deaths per 1,000 live births in 2017. We can, and must, do better.

One of the major contributing factors to infant mortality is preterm birth. Defined as birth occurring prior to 37 weeks’ gestation, preterm birth is associated with a myriad of severe neonatal sequelae: low birth weight, bacterial sepsis, neonatal hemorrhage, and respiratory distress syndrome, among others. Therefore, many within the clinical and biomedical research spheres recognize that preventing preterm birth means reducing infant deaths.

However, therein lies the conundrum. We know very little about what causes preterm birth, which renders the current therapeutic strategies – such as use of progesterone supplements or cerclage placement – good for some but not all patients. It is thus vital to continue research to unravel the underlying mechanisms of preterm birth.

A promising area of investigation is the field of microbiome research, which has made great strides in advancing our awareness of the critical role of the millions of organisms living on and within us in maintaining health and fighting disease. For example, we now realize that eradicating all the commensals in our gastrointestinal tract has unintended and very negative consequences and, for patients whose good bacteria have been eliminated, fecal transplant is a therapeutic option. Therefore, it stands to reason that the microbes found in the vagina contribute significantly to women’s overall reproductive health.

The publication of the groundbreaking study characterizing the vaginal microbiome species in reproductive-age women opened new avenues of research into how these organisms contribute to women’s health. Importantly, this work, led initially by Jacques Ravel, PhD, a professor in the department of microbiology & immunology and associate director of the Institute for Genome Sciences at the University of Maryland School of Medicine, has spawned additional investigations into the potential role of the vaginal microbiome in preterm birth.

To provide some insight into the research around how the microorganisms in the vagina may induce or prevent preterm birth is our guest author, Michal A. Elovitz, MD, 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.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

A novel coronavirus originating in Wuhan, China, has killed more than 2,800 people and infected more than 81,000 individuals globally. Public health officials around the world and in the United States are working together to contain the outbreak.

Bunwit/Getty Images

There are 57 confirmed cases in the United States, including 18 people evacuated from the Diamond Princess, a cruise ship docked in Yokohama, Japan.¹ But the focus on coronavirus, even in early months of the epidemic, serves as an opportunity to revisit the spread of viral disease in hospital settings.
 

Multiple points of viral entry

In truth, most hospitals are well prepared for the coronavirus, starting with the same place they prepare for most infectious disease epidemics – the emergency department. Patients who seek treatment for early onset symptoms may start with their primary care physicians, but increasing numbers of patients with respiratory concerns and/or infection-related symptoms will first seek medical attention in an emergency care setting.²

Many experts have acknowledged the ED as a viral point of entry, including the American College of Emergency Physicians (ACEP), which produced an excellent guide for management of influenza that details prevention, diagnoses, and treatment protocols in an ED setting.³

But another important, and often forgotten, point of entry in a hospital setting is the obstetrical (OB) Labor & Delivery (L&D) department. Although triage for most patients begins in the main ED, in almost every hospital in the United States, women who present with pregnancy-related issues are sent directly to and triaged in L&D, where – when the proper protocols are not in place – they may transmit viral infection to others.

Pregnancy imparts higher risk

“High risk” is often associated with older, immune-compromised adults. But pregnant women who may appear “healthy” are actually in a state that a 2015 study calls “immunosuppressed” whereby the “… pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus.”⁴ Pregnant women, or women with newborns or babies, are at higher risk when exposed to viral infection, with a higher mortality risk than the general population.⁵ In the best cases, women who contract viral infections are treated carefully and recover fully. In the worst cases, they end up on ventilators and can even die as a result.

Although we are still learning about the Wuhan coronavirus, we already know it is a respiratory illness with a lot of the same characteristics as the influenza virus, and that it is transmitted through droplets (such as a sneeze) or via bodily secretions. Given the extreme vulnerability and physician exposure of women giving birth – in which not one, but two lives are involved – viruses like coronavirus can pose extreme risk. What’s more, public health researchers are still learning about potential transmission of coronavirus from mothers to babies. In the international cases of infant exposure to coronavirus, the newborn showed symptoms within 36 hours of being born, but it is unclear if exposure happened in utero or was vertical transmission after birth.⁶

Role of OB hospitalists in identifying risk and treating viral infection

Regardless of the type of virus, OB hospitalists are key to screening for viral exposure and care for women, fetuses, and newborns. Given their 24/7 presence and experience with women in L&D, they must champion protocols and precautions that align with those in an ED.

For coronavirus, if a woman presents in L&D with a cough, difficulty breathing, or signs of pneumonia, clinicians should be accustomed to asking about travel to China within the last 14 days and whether the patient has been around someone who has recently traveled to China. If the answer to either question is yes, the woman needs to be immediately placed in a single patient room at negative pressure relative to the surrounding areas, with a minimum of six air changes per hour.

Diagnostic testing should immediately follow. The U.S. Food and Drug Administration just issued Emergency Use Authorization (EUA) for the first commercially-available coronavirus diagnostic test, allowing the use of the test at any lab across the country qualified by the Centers for Disease Control and Prevention.⁷

If exposure is suspected, containment is paramount until definitive results of diagnostic testing are received. The CDC recommends “Standard Precautions,” which assume that every person is potentially infected or colonized with a pathogen that could be transmitted in the health care setting. These precautions include hand hygiene and personal protective equipment (PPE) to ensure health care workers are not exposed.⁸

In short, protocols in L&D should mirror those of the ED. But in L&D, clinicians and staff haven’t necessarily been trained to look for or ask for these conditions. Hospitalists can educate their peers and colleagues and advocate for changes at the administrative level.

Biggest current threat: The flu

The coronavirus may eventually present a threat in the United States, but as yet, it is a largely unrealized one. From the perspective of an obstetrician, more immediately concerning is the risk of other viral infections. Although viruses like Ebola and Zika capture headlines, influenza remains the most serious threat to pregnant women in the United States.

According to an article by my colleague, Dr. Mark Simon, “pregnant women and their unborn babies are especially vulnerable to influenza and are more likely to develop serious complications from it … pregnant women who develop the flu are more likely to give birth to children with birth defects of the brain and spine.”⁹

As of Feb. 1, 2020, the CDC estimates there have been at least 22 million flu illnesses, 210,000 hospitalizations, and 12,000 deaths from flu in the 2019-2020 flu season.¹⁰ But the CDC data also suggest that only 54% of pregnant women were vaccinated for influenza in 2019 before or during their pregnancy.¹¹ Hospitalists should ensure that patients diagnosed with flu are quickly and safely treated with antivirals at all stages of their pregnancy to keep them and their babies safe, as well as keep others safe from infection.

Hospitalists can also advocate for across-the-board protocols for the spread of viral illness. The same protocols that protect us from the flu will also protect against coronavirus and viruses that will emerge in the future. Foremost, pregnant women, regardless of trimester, need to receive a flu shot. Women who are pregnant and receive a flu shot can pass on immunity in vitro, and nursing mothers can deliver immunizing agents in their breast milk to their newborn.

Given that hospitalists serve in roles as patient-facing physicians, we should be doing more to protect the public from viral spread, whether coronavirus, influenza, or whatever new viruses the future may hold.
 

Dr. Dimino is a board-certified ob.gyn. and a Houston-based OB hospitalist with Ob Hospitalist Group. She serves as a faculty member of the TexasAIM Plus Obstetric Hemorrhage Learning Collaborative and currently serves on the Texas Medical Association Council of Science and Public Health.

References

1. The New York Times. Tracking the Coronavirus Map: Tracking the Spread of the Outbreak. Accessed Feb 24, 2020.

2. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Accessed Feb 10, 2020.

3. Influenza Emergency Department Best Practices. ACEP Public Health & Injury Prevention Committee, Epidemic Expert Panel, https://www.acep.org/globalassets/uploads/uploaded-files/acep/by-medical-focus/influenza-emergency-department-best-practices.pdf.

4. Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infections during pregnancy. Am J Reprod Immunol. 2015;73(3):199-213.

5. Kwon JY, Romero R, Mor G. New insights into the relationship between viral infection and pregnancy complications. Am J Reprod Immunol. 2014;71:387-390.

6. BBC. Coronavirus: Newborn becomes youngest person diagnosed with virus. Accessed Feb 10, 2020.

7. FDA press release. FDA Takes Significant Step in Coronavirus Response Efforts, Issues Emergency Use Authorization for the First 2019 Novel Coronavirus Diagnostic. Feb 4, 2020.

8. CDC. Interim Infection Prevention and Control Recommendations for Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) or Persons Under Investigation for 2019-nCoV in Healthcare Settings. Accessed Feb 10, 2020.

9. STAT First Opinion. Two-thirds of pregnant women aren’t getting the flu vaccine. That needs to change. Jan 18, 2018.

10. CDC. Weekly U.S. Influenza Surveillance Report, Key Updates for Week 5, ending February 1, 2020.

11. CDC. Vaccinating Pregnant Women Protects Moms and Babies. Accessed Feb 10, 2020.

A novel coronavirus originating in Wuhan, China, has killed more than 2,800 people and infected more than 81,000 individuals globally. Public health officials around the world and in the United States are working together to contain the outbreak.

Bunwit/Getty Images

There are 57 confirmed cases in the United States, including 18 people evacuated from the Diamond Princess, a cruise ship docked in Yokohama, Japan.¹ But the focus on coronavirus, even in early months of the epidemic, serves as an opportunity to revisit the spread of viral disease in hospital settings.
 

Multiple points of viral entry

In truth, most hospitals are well prepared for the coronavirus, starting with the same place they prepare for most infectious disease epidemics – the emergency department. Patients who seek treatment for early onset symptoms may start with their primary care physicians, but increasing numbers of patients with respiratory concerns and/or infection-related symptoms will first seek medical attention in an emergency care setting.²

Many experts have acknowledged the ED as a viral point of entry, including the American College of Emergency Physicians (ACEP), which produced an excellent guide for management of influenza that details prevention, diagnoses, and treatment protocols in an ED setting.³

But another important, and often forgotten, point of entry in a hospital setting is the obstetrical (OB) Labor & Delivery (L&D) department. Although triage for most patients begins in the main ED, in almost every hospital in the United States, women who present with pregnancy-related issues are sent directly to and triaged in L&D, where – when the proper protocols are not in place – they may transmit viral infection to others.

Pregnancy imparts higher risk

“High risk” is often associated with older, immune-compromised adults. But pregnant women who may appear “healthy” are actually in a state that a 2015 study calls “immunosuppressed” whereby the “… pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus.”⁴ Pregnant women, or women with newborns or babies, are at higher risk when exposed to viral infection, with a higher mortality risk than the general population.⁵ In the best cases, women who contract viral infections are treated carefully and recover fully. In the worst cases, they end up on ventilators and can even die as a result.

Although we are still learning about the Wuhan coronavirus, we already know it is a respiratory illness with a lot of the same characteristics as the influenza virus, and that it is transmitted through droplets (such as a sneeze) or via bodily secretions. Given the extreme vulnerability and physician exposure of women giving birth – in which not one, but two lives are involved – viruses like coronavirus can pose extreme risk. What’s more, public health researchers are still learning about potential transmission of coronavirus from mothers to babies. In the international cases of infant exposure to coronavirus, the newborn showed symptoms within 36 hours of being born, but it is unclear if exposure happened in utero or was vertical transmission after birth.⁶

Role of OB hospitalists in identifying risk and treating viral infection

Regardless of the type of virus, OB hospitalists are key to screening for viral exposure and care for women, fetuses, and newborns. Given their 24/7 presence and experience with women in L&D, they must champion protocols and precautions that align with those in an ED.

For coronavirus, if a woman presents in L&D with a cough, difficulty breathing, or signs of pneumonia, clinicians should be accustomed to asking about travel to China within the last 14 days and whether the patient has been around someone who has recently traveled to China. If the answer to either question is yes, the woman needs to be immediately placed in a single patient room at negative pressure relative to the surrounding areas, with a minimum of six air changes per hour.

Diagnostic testing should immediately follow. The U.S. Food and Drug Administration just issued Emergency Use Authorization (EUA) for the first commercially-available coronavirus diagnostic test, allowing the use of the test at any lab across the country qualified by the Centers for Disease Control and Prevention.⁷

If exposure is suspected, containment is paramount until definitive results of diagnostic testing are received. The CDC recommends “Standard Precautions,” which assume that every person is potentially infected or colonized with a pathogen that could be transmitted in the health care setting. These precautions include hand hygiene and personal protective equipment (PPE) to ensure health care workers are not exposed.⁸

In short, protocols in L&D should mirror those of the ED. But in L&D, clinicians and staff haven’t necessarily been trained to look for or ask for these conditions. Hospitalists can educate their peers and colleagues and advocate for changes at the administrative level.

Biggest current threat: The flu

The coronavirus may eventually present a threat in the United States, but as yet, it is a largely unrealized one. From the perspective of an obstetrician, more immediately concerning is the risk of other viral infections. Although viruses like Ebola and Zika capture headlines, influenza remains the most serious threat to pregnant women in the United States.

According to an article by my colleague, Dr. Mark Simon, “pregnant women and their unborn babies are especially vulnerable to influenza and are more likely to develop serious complications from it … pregnant women who develop the flu are more likely to give birth to children with birth defects of the brain and spine.”⁹

As of Feb. 1, 2020, the CDC estimates there have been at least 22 million flu illnesses, 210,000 hospitalizations, and 12,000 deaths from flu in the 2019-2020 flu season.¹⁰ But the CDC data also suggest that only 54% of pregnant women were vaccinated for influenza in 2019 before or during their pregnancy.¹¹ Hospitalists should ensure that patients diagnosed with flu are quickly and safely treated with antivirals at all stages of their pregnancy to keep them and their babies safe, as well as keep others safe from infection.

Hospitalists can also advocate for across-the-board protocols for the spread of viral illness. The same protocols that protect us from the flu will also protect against coronavirus and viruses that will emerge in the future. Foremost, pregnant women, regardless of trimester, need to receive a flu shot. Women who are pregnant and receive a flu shot can pass on immunity in vitro, and nursing mothers can deliver immunizing agents in their breast milk to their newborn.

Given that hospitalists serve in roles as patient-facing physicians, we should be doing more to protect the public from viral spread, whether coronavirus, influenza, or whatever new viruses the future may hold.
 

Dr. Dimino is a board-certified ob.gyn. and a Houston-based OB hospitalist with Ob Hospitalist Group. She serves as a faculty member of the TexasAIM Plus Obstetric Hemorrhage Learning Collaborative and currently serves on the Texas Medical Association Council of Science and Public Health.

References

1. The New York Times. Tracking the Coronavirus Map: Tracking the Spread of the Outbreak. Accessed Feb 24, 2020.

2. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Accessed Feb 10, 2020.

3. Influenza Emergency Department Best Practices. ACEP Public Health & Injury Prevention Committee, Epidemic Expert Panel, https://www.acep.org/globalassets/uploads/uploaded-files/acep/by-medical-focus/influenza-emergency-department-best-practices.pdf.

4. Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infections during pregnancy. Am J Reprod Immunol. 2015;73(3):199-213.

5. Kwon JY, Romero R, Mor G. New insights into the relationship between viral infection and pregnancy complications. Am J Reprod Immunol. 2014;71:387-390.

6. BBC. Coronavirus: Newborn becomes youngest person diagnosed with virus. Accessed Feb 10, 2020.

7. FDA press release. FDA Takes Significant Step in Coronavirus Response Efforts, Issues Emergency Use Authorization for the First 2019 Novel Coronavirus Diagnostic. Feb 4, 2020.

8. CDC. Interim Infection Prevention and Control Recommendations for Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) or Persons Under Investigation for 2019-nCoV in Healthcare Settings. Accessed Feb 10, 2020.

9. STAT First Opinion. Two-thirds of pregnant women aren’t getting the flu vaccine. That needs to change. Jan 18, 2018.

10. CDC. Weekly U.S. Influenza Surveillance Report, Key Updates for Week 5, ending February 1, 2020.

11. CDC. Vaccinating Pregnant Women Protects Moms and Babies. Accessed Feb 10, 2020.

A novel coronavirus originating in Wuhan, China, has killed more than 2,800 people and infected more than 81,000 individuals globally. Public health officials around the world and in the United States are working together to contain the outbreak.

Bunwit/Getty Images

There are 57 confirmed cases in the United States, including 18 people evacuated from the Diamond Princess, a cruise ship docked in Yokohama, Japan.¹ But the focus on coronavirus, even in early months of the epidemic, serves as an opportunity to revisit the spread of viral disease in hospital settings.
 

Multiple points of viral entry

In truth, most hospitals are well prepared for the coronavirus, starting with the same place they prepare for most infectious disease epidemics – the emergency department. Patients who seek treatment for early onset symptoms may start with their primary care physicians, but increasing numbers of patients with respiratory concerns and/or infection-related symptoms will first seek medical attention in an emergency care setting.²

Many experts have acknowledged the ED as a viral point of entry, including the American College of Emergency Physicians (ACEP), which produced an excellent guide for management of influenza that details prevention, diagnoses, and treatment protocols in an ED setting.³

But another important, and often forgotten, point of entry in a hospital setting is the obstetrical (OB) Labor & Delivery (L&D) department. Although triage for most patients begins in the main ED, in almost every hospital in the United States, women who present with pregnancy-related issues are sent directly to and triaged in L&D, where – when the proper protocols are not in place – they may transmit viral infection to others.

Pregnancy imparts higher risk

“High risk” is often associated with older, immune-compromised adults. But pregnant women who may appear “healthy” are actually in a state that a 2015 study calls “immunosuppressed” whereby the “… pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus.”⁴ Pregnant women, or women with newborns or babies, are at higher risk when exposed to viral infection, with a higher mortality risk than the general population.⁵ In the best cases, women who contract viral infections are treated carefully and recover fully. In the worst cases, they end up on ventilators and can even die as a result.

Although we are still learning about the Wuhan coronavirus, we already know it is a respiratory illness with a lot of the same characteristics as the influenza virus, and that it is transmitted through droplets (such as a sneeze) or via bodily secretions. Given the extreme vulnerability and physician exposure of women giving birth – in which not one, but two lives are involved – viruses like coronavirus can pose extreme risk. What’s more, public health researchers are still learning about potential transmission of coronavirus from mothers to babies. In the international cases of infant exposure to coronavirus, the newborn showed symptoms within 36 hours of being born, but it is unclear if exposure happened in utero or was vertical transmission after birth.⁶

Role of OB hospitalists in identifying risk and treating viral infection

Regardless of the type of virus, OB hospitalists are key to screening for viral exposure and care for women, fetuses, and newborns. Given their 24/7 presence and experience with women in L&D, they must champion protocols and precautions that align with those in an ED.

For coronavirus, if a woman presents in L&D with a cough, difficulty breathing, or signs of pneumonia, clinicians should be accustomed to asking about travel to China within the last 14 days and whether the patient has been around someone who has recently traveled to China. If the answer to either question is yes, the woman needs to be immediately placed in a single patient room at negative pressure relative to the surrounding areas, with a minimum of six air changes per hour.

Diagnostic testing should immediately follow. The U.S. Food and Drug Administration just issued Emergency Use Authorization (EUA) for the first commercially-available coronavirus diagnostic test, allowing the use of the test at any lab across the country qualified by the Centers for Disease Control and Prevention.⁷

If exposure is suspected, containment is paramount until definitive results of diagnostic testing are received. The CDC recommends “Standard Precautions,” which assume that every person is potentially infected or colonized with a pathogen that could be transmitted in the health care setting. These precautions include hand hygiene and personal protective equipment (PPE) to ensure health care workers are not exposed.⁸

In short, protocols in L&D should mirror those of the ED. But in L&D, clinicians and staff haven’t necessarily been trained to look for or ask for these conditions. Hospitalists can educate their peers and colleagues and advocate for changes at the administrative level.

Biggest current threat: The flu

The coronavirus may eventually present a threat in the United States, but as yet, it is a largely unrealized one. From the perspective of an obstetrician, more immediately concerning is the risk of other viral infections. Although viruses like Ebola and Zika capture headlines, influenza remains the most serious threat to pregnant women in the United States.

According to an article by my colleague, Dr. Mark Simon, “pregnant women and their unborn babies are especially vulnerable to influenza and are more likely to develop serious complications from it … pregnant women who develop the flu are more likely to give birth to children with birth defects of the brain and spine.”⁹

As of Feb. 1, 2020, the CDC estimates there have been at least 22 million flu illnesses, 210,000 hospitalizations, and 12,000 deaths from flu in the 2019-2020 flu season.¹⁰ But the CDC data also suggest that only 54% of pregnant women were vaccinated for influenza in 2019 before or during their pregnancy.¹¹ Hospitalists should ensure that patients diagnosed with flu are quickly and safely treated with antivirals at all stages of their pregnancy to keep them and their babies safe, as well as keep others safe from infection.

Hospitalists can also advocate for across-the-board protocols for the spread of viral illness. The same protocols that protect us from the flu will also protect against coronavirus and viruses that will emerge in the future. Foremost, pregnant women, regardless of trimester, need to receive a flu shot. Women who are pregnant and receive a flu shot can pass on immunity in vitro, and nursing mothers can deliver immunizing agents in their breast milk to their newborn.

Given that hospitalists serve in roles as patient-facing physicians, we should be doing more to protect the public from viral spread, whether coronavirus, influenza, or whatever new viruses the future may hold.
 

Dr. Dimino is a board-certified ob.gyn. and a Houston-based OB hospitalist with Ob Hospitalist Group. She serves as a faculty member of the TexasAIM Plus Obstetric Hemorrhage Learning Collaborative and currently serves on the Texas Medical Association Council of Science and Public Health.

References

1. The New York Times. Tracking the Coronavirus Map: Tracking the Spread of the Outbreak. Accessed Feb 24, 2020.

2. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Accessed Feb 10, 2020.

3. Influenza Emergency Department Best Practices. ACEP Public Health & Injury Prevention Committee, Epidemic Expert Panel, https://www.acep.org/globalassets/uploads/uploaded-files/acep/by-medical-focus/influenza-emergency-department-best-practices.pdf.

4. Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infections during pregnancy. Am J Reprod Immunol. 2015;73(3):199-213.

5. Kwon JY, Romero R, Mor G. New insights into the relationship between viral infection and pregnancy complications. Am J Reprod Immunol. 2014;71:387-390.

6. BBC. Coronavirus: Newborn becomes youngest person diagnosed with virus. Accessed Feb 10, 2020.

7. FDA press release. FDA Takes Significant Step in Coronavirus Response Efforts, Issues Emergency Use Authorization for the First 2019 Novel Coronavirus Diagnostic. Feb 4, 2020.

8. CDC. Interim Infection Prevention and Control Recommendations for Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) or Persons Under Investigation for 2019-nCoV in Healthcare Settings. Accessed Feb 10, 2020.

9. STAT First Opinion. Two-thirds of pregnant women aren’t getting the flu vaccine. That needs to change. Jan 18, 2018.

10. CDC. Weekly U.S. Influenza Surveillance Report, Key Updates for Week 5, ending February 1, 2020.

11. CDC. Vaccinating Pregnant Women Protects Moms and Babies. Accessed Feb 10, 2020.