MDedge ObGyn

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.

In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

.

In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

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In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

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Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

sworcester@mdedge.com

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

sworcester@mdedge.com

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

sworcester@mdedge.com

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER

ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)

HPV vaccine for older ObGyns?

I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?

Gus Barkett, DO

Muskegon, Michigan

Dr. Barbieri responds

I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.

EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?

ANDREW M. KAUNITZ, MD (AUGUST 2020)

Discordant results on screening mammography

In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.¹ Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.

I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.

Lisa Gennari, MD

Cincinnati, Ohio

Reference

1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.

Dr. Kaunitz responds

I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.¹ That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).

In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.

Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.

Reference 
 

1. Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.

Continue to: NEW HORMONAL MEDICAL TREATMENT...

NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS

ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)

New AUB medical treatment

I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?

Geoffrey J. Zann, MD, MBA

Boca Raton, Florida

Dr. Barbieri responds

Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.

In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.^1,2
 

Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.^1,2

I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.

References 

1. Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
2. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.

9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER

ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)

HPV vaccine for older ObGyns?

I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?

Gus Barkett, DO

Muskegon, Michigan

Dr. Barbieri responds

I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.

EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?

ANDREW M. KAUNITZ, MD (AUGUST 2020)

Discordant results on screening mammography

In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.¹ Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.

I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.

Lisa Gennari, MD

Cincinnati, Ohio

Reference

1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.

Dr. Kaunitz responds

I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.¹ That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).

In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.

Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.

Reference 
 

1. Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.

Continue to: NEW HORMONAL MEDICAL TREATMENT...

NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS

ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)

New AUB medical treatment

I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?

Geoffrey J. Zann, MD, MBA

Boca Raton, Florida

Dr. Barbieri responds

Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.

In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.^1,2
 

Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.^1,2

I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.

References 

1. Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
2. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.

9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER

ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)

HPV vaccine for older ObGyns?

I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?

Gus Barkett, DO

Muskegon, Michigan

Dr. Barbieri responds

I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.

EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?

ANDREW M. KAUNITZ, MD (AUGUST 2020)

Discordant results on screening mammography

In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.¹ Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.

I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.

Lisa Gennari, MD

Cincinnati, Ohio

Reference

1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.

Dr. Kaunitz responds

I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.¹ That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).

In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.

Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.

Reference 
 

1. Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.

Continue to: NEW HORMONAL MEDICAL TREATMENT...

NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS

ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)

New AUB medical treatment

I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?

Geoffrey J. Zann, MD, MBA

Boca Raton, Florida

Dr. Barbieri responds

Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.

In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.^1,2
 

Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.^1,2

I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.

References 

1. Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
2. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.